REGISTRY OF TOXIC EFFECTS OF CHEMICAL SUBSTANCES (RTECS速)
COMPREHENSIVE GUIDE TO THE RTECS速
Symyx Technologies, Inc.
2440 Camino Ramon, Suite 300
San Ramon, CA 94583
December 2007
Comprehensive Guide to RTECS
INTRODUCTION
This Comprehensive Guide to the Registry of Toxic Effects of Chemical Substances (RTECS速) describes
the types of data and their format.
RTECS速 Data Selection, Evaluation, and Use
The toxicity information appearing in the Registry is derived from reports of the toxic effects of chemical
substances. The absence of a substance from the Registry does not imply that the substance is non-toxic. A
substance may not appear for a variety of reasons. Four reasons include the following: (1) the test results
could not be cited because the protocol of the study did not meet the RTECS速 selection criteria; (2) the
substance has not yet been tested; (3) the substance has been tested, but the RTECS速 literature search has
not yet uncovered the data; or (4) the data are not publicly available.
RTECS速 consists of tabulations of the lowest dose reported to have caused the listed toxic effect in the
designated species by the designated route of administration. The Registry includes substances that have
been selected primarily for the toxic effect produced by single doses. However, when the toxic effect has
been described by the author as mutagenic, tumorigenic, or as a reproductive toxicant, the toxic dose data
are reported for both single and multiple dose studies. Other Multiple Dose Toxicity Data and
References,? includes any other effects from multiple dose studies.
For human data, any reported adverse effect is included.
The report of the lowest total dose administered to produce the toxic effect is given preference although
some editorial license is taken so that additional references might be cited. No restrictions are placed on the
amount of a substance producing death in an experimental animal nor on the time period over which the
dose was given. The inclusion of data with the notation LD50>__mg/kg? or LC50>__ ppm? is intended to
indicate that the substance cited has been tested up to the indicated level without reaching that level of
toxicity.
The Detailed File Description of RTECS速 provides details of the format and content of the various toxicity
data lines. Studies reporting primary irritation to the skin and eyes are described in Section 10; Section 11
describes the mutagenic test systems and the organisms and cell types used in mutagenic testing; elements
of the reproductive effects toxicity lines are described in Section 12; reports of positive or equivocal
tumorigenic effects included in the Registry are described in Section 13. (Other tumorigenic data may be
found on the International Agency for Research on Cancer [IARC] review lines [described in Section 17b]
and the NTP carcinogenesis bioassay status lines [Section 20d]). Section 14 describes acute toxicity data,
including the system of Toxic Effects Codes (TEC). Other Multiple Dose Data is described in Section 15.
Toxicity data reported in the literature are transformed into Registry format using the criteria presented in
the Detailed File Description. The quality of the data on which the report is based has not been evaluated.
In most cases no attempt is made to resolve any questions about the data.
It is not the purpose of the Registry to quantitate a hazard through the use of the toxic concentration or dose
data that are presented with each substance. UNDER NO CIRCUMSTANCES CAN THE TOXIC
DOSE VALUES PRESENTED WITH THESE CHEMICAL SUBSTANCES BE CONSIDERED
DEFINITIVE VALUES FOR DESCRIBING SAFE VERSUS TOXIC DOSES FOR HUMAN
EXPOSURE.
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General Comments
The Editor will appreciate assistance from representatives of the industrial, academic, and governmental
communities in supplying data for this Registry. Such assistance may be offered in the form of reprints of
scientific publications, technical data sheets, sales or promotional material, other publicly available
reference material, and data presented on unpublished studies. All material received will be considered to
be in the public domain and as such may be made available to any person or organization. Data cited and
published in the Registry will be selected according to the criteria presented herein. Information on errors
in the file is also solicited as are general comments or recommendations. All correspondence should be
addressed to:
The Editor
Registry of Toxic Effects of Chemical Substances
Symyx Technologies, Inc.
2440 Camino Ramon, Suite 300
San Ramon, CA 94583
E-mail address: http://www.mdl.com/support/contact/worldwide.jsp
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DETAILED FILE DESCRIPTION
Substance Selection
Substances Included: For the purpose of this publication, the phrase all known toxic substances? is
interpreted by the Editor to mean all mined, manufactured, processed, synthesized, and naturally occurring
inorganic and organic compounds. The list of substances includes drugs, food additives, preservatives, ores,
pesticides, dyes, detergents, lubricants, soaps, plastics, extracts from plant and animal sources, plants and
animals which are toxic by contact or consumption, and industrial intermediates and waste products from
production processes. Some of the information in the file thus refers to materials whose composition is not
perfectly known. The chemical substances included in this list are assumed to exhibit the reported toxic
effect in their pure state unless otherwise noted. However, even in the case of a supposedly pure?
substance, there is usually some degree of uncertainty as to its exact composition and the impurities which
may be present. This possibility must be considered in attempting to interpret the data presented since the
toxic effects observed could in some cases be caused by a contaminant.
Substances Excluded: Excluded from the Registry are trade name products representing compounded or
formulated proprietary mixtures available as commercial products. These exclusions are necessary because
of difficulties in assessing the contribution of each component of a mixture to the toxicity of that substance
and because the formulation of a product is often changed by varying the components, their concentration,
or the purity of the ingredients. Commercial product trade names are included, however, when they
represent a single active chemical entity or a well-defined mixture of relatively consistent composition.
Radioactive substances are included, but the effect reported is the chemically produced effect rather than
the radiation effect.
Format
All substance prime names and synonyms in the file are listed in alphabetical order, ignoring special
characters, such as numerals, Greek letters, and prefixes indicating substituent locations, and
stereochemical or other structural features. These components are taken into account for secondary
ordering in ascending alphabetical and numerical order.
Each substance prime name is identified by a nine-position sequence number (two letters and seven
numbers) which varies directly with the alphabetic sequence of the name, so that toluene, for example, has
a higher number than benzene. Each synonym is cross-referenced to its appropriate prime name sequence
number. The sequence number is simply an identifier assigned alphabetically and numerically to each
substance in the Registry. It is not intentionally related to the toxicity or structure of the compound
although compounds with alphabetically similar names and, in some cases, therefore, similar structures are
grouped together.
For each prime name sequence number the following data are provided when available: the substance
prime name and synonyms; a description of the substance (where necessary); date when the RTECS速 data
records last updated; CAS Number; Beilstein Reference Number; RTECS速 Number; molecular formula;
molecular weight; Wiswesser Line Notation (WLN); compound descriptor code(s); primary irritation;
mutagenic, reproductive, and tumorigenic effects data; acute toxicity data; other multiple dose toxicity data;
ACGIH Threshold Limit Values, IARC Monograph reviews; toxicological reviews; existing Federal
standards; NIOSH Criteria Documents, Current Intelligence Bulletins, recommended exposure levels,
surveillance data and analytical methods; the NTP Carcinogenesis Testing Program; and the EPA TSCA
Inventory, GENE-TOX, TSCATS Database, Section 8(a) preliminary assessment, Section 8(b) chemical
inventory, and Section 8(e) status programs. Each data line and citation is referenced by CODEN to the
source from which the information was extracted. A list of CODEN abbreviations and their respective titles
is provided in the CODEN Master File. Each field in the RTECS速 data record is discussed below.
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1. Substance Prime Name (Data Type A). The prime name of each substance in the Registry is
derived from the nomenclature used by the American Chemical Societys Chemical Abstracts
Service (CAS) in the Collective Index of Chemical Abstracts. The names are given in the inverted
form. The complete RTECS速 data record for each substance follows its prime name.
Some entries, however, appear under the chemical or descriptive names used in the reference from
which the toxic data were obtained. This is particularly true for those substances of questionable
composition, such as plant or animal extracts. These prime names are accompanied by a brief
description or definition (DEF?) (Data Type C) listing the source of the substance, a general
statement of constituents, or other pertinent information, and the CODEN citation of the reference
that contained the definition.
Synonym cross references are tabulated as Data Type B.
2. Update (Data Type E). This field specifies when the data record of a substance was last changed.
The format is YYYYMM, e.g., 198105 = May 1981. All 33,929 substances in the file as of
January 1979 were initialized with a date of 197901. When data on a new substance are first input
to the file, the update field is assigned the month and year of entry. When the data record is
subsequently revised, the date is changed to reflect the month and year the change was made. Any
revision, for example, deletion of an invalid synonym, addition of new toxicity data, change in the
NTP status, or correction of a molecular formula, will cause the update field of the substance to
change.
3. Chemical Registry Number (Data Type D). There are two types of chemical registry numbers
included in this field. The CAS Registry Number速 is a numeric designation assigned by the
Chemical Abstracts Service of the American Chemical Society that uniquely identifies a specific
chemical compound, regardless of the name or nomenclature system used. Because CAS, on
occasion, assigns new numbers to selected chemicals without withdrawing the previously assigned
numbers, confusion sometimes arises. This situation occurs when a substance is better described
or more accurately identified. RTECS速 lists the most recent CAS number available for a chemical
and, to preserve continuity and prevent confusion, includes a second CAS number line which will
list PREVIOUS? CAS numbers. Up to ten (10) such previous CAS numbers will be listed for a
substance.
An additional set of Registry Numbers for organic chemicals is also included in this data field.
These are the Beilstein Registry Numbers (BRN) and Beilstein Handbook References originally
created by the Beilstein Institute of Frankfurt-am-Main, Germany. This database currently
maintained by Elsevier is a listing of structures, properties, and reactions. Each of these numbers
is assigned a specific line number within the field.
RTECS速 Number (Data Type G). The RTECS速 number is a unique 9-position alphanumeric
4.
designation assigned to each prime chemical name. These numbers are permanently assigned and
will not change. (They are not to be confused with the alphanumeric sequence numbers by which
the file is sorted.)
5. Molecular Weight (MW) (Data Type H). The molecular weight is calculated from the molecular
formula using standard elemental molecular weights (carbon = 12.01).
6. Molecular Formula (MF) (Data Type F). The molecular formula designating the elemental
composition of the substances is structured according the Hill System (Journal of the American
Chemical Society, 22(8):478-494, 1900), in which carbon and hydrogen (if present) are listed first,
followed by the other elemental symbols in alphabetical order. The formulas for compounds that
do not contain carbon are ordered strictly alphabetically by elemental symbol. Compounds such as
salts or those containing waters of hydration have molecular formulas incorporating the CAS dot-
disconnect convention, in which the components are listed individually and separated by a period.
The individual components of the formula are generally given in order of decreasing carbon atom
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Comprehensive Guide to RTECS
count and component ratios. A lowercase x? indicates that the ratio is unknown. A lower case n?
indicates a repeating polymer-like structure. The formula is obtained from one of the cited
references or a chemical reference text, or is derived from the name of the substance.
7. Wiswesser Line Notation (WLN) (Data Type J). The Wiswesser Line Notation is a line-formula
chemical notation that precisely and concisely describes the structural formula of a chemical
compound. This linear representation for a three-dimensional structure facilitates substructure
searching for special functional groups and constituents that are part of the molecule. The WLNs
allow machine retrieval by chemical characteristics.
8. Synonyms (Data Type L). Synonyms for the substance prime name are listed alphabetically
according to the rule described under Format. Synonyms include other chemical names, trade
names, common or general names, foreign language names (with the language in parentheses), or
codes. Some synonyms consist wholly or in part of registered trademarks. These trademarks are
not identified as such in the RTECS速 file because of limitations in the computer character sets
used to produce the Registry. The Editor is aware of the problem of trademarks becoming generic
trade names through common usage. While the Registry does not presently have a mechanism for
noting trademarks, the lack of the appropriate registered trademark symbol does not imply that the
trademarks contained herein are considered generic synonyms. Those trade names that are known
to be obsolete, either because production and marketing of the substance has ceased or because the
compound is currently manufactured under another name, are indicated with the abbreviation
?(Obs.).?
The American Conference of Governmental Industrial Hygienists (ACGIH) in their listing of
Threshold Limit Values (TLV速), Department of Transportation (DOT) in the Hazardous
Substances List, and the Occupational Safety and Health Administration (OSHA) in the listing of
Permissible Exposure Limits (PELs) on occasion use other than the prime chemical name in their
designations. For the convenience of the user, RTECS速 adds to the appropriate synonym name in
parentheses the designation ACGIH, DOT, and/or OSHA. For example, the prime name chemical
2-Pentanone, 4-Hydroxy-4-Methyl includes in its synonym field the following: Diacetone Alcohol
(ACGIH:OSHA).
The reader is cautioned that some synonyms, particularly common names, may be ambiguous and
refer to more than one substance. The substances may or may not be chemically similar. For
example, some common names are applied in the literature both to a particular compound and to
various metallic salts of that compound. In addition, the Registrys list of synonyms is not
exhaustive, and the file may not include an entry for every existing use of a particular common
name. Therefore, when using a synonym to look up data in the Registry, care must be taken to
ensure that the substance record retrieved is for the particular substance in question and not for one
with an identical common name.
9. Compound Descriptor Codes (Data Type N). For each code found in position 10, a one-letter code
appears in column 14. These codes are listed below and can be used as selection keys to extract
defined subfiles of the master file. A substance entry may contain multiple descriptor codes.
CODE COMPOUND DESCRIPTION
A Agricultural Chemical
C Tumorigen
D Drug
H Hormone
M Mutagen
N Natural Product
O Organometallic
P Human Data
S Primary Irritant
T Reproductive Effector
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This compound descriptor field was developed as a search tool.
The RTECS速 compound descriptor codes do not represent an evaluation of the toxicity of a
substance, nor are the codes all-inclusive with respect to use (that is, there may be some
substances in the RTECS速 file that should be, but are not, coded as belonging to certain
application classes). The codes must be interpreted only in conjunction with the other information
found in each substance data record.
The RTECS速 descriptor codes fall into two categories: (1) those based on the types of toxicity data
found in the substance data records and (2) those based on related information found in the
references from which the data were extracted. In the first category are the following descriptor
codes: tumorigen, mutagen, reproductive effector, primary irritant, and human data. As mentioned,
these five classifications do not represent an evaluation of the overall toxicity of a substance.
Rather, they indicate the type(s)of toxicity data line(s) found in the substance data record.
The descriptor code Tumorigen? is something of a misnomer. More specifically, it denotes a
substance with positive or negative tumorigen citation(s).? That is, any substance with the
descriptor code tumorigen? will have one or more of the following in its RTECS速 data record:
? One or more tumorigenic data lines (Data Type S, see Section 13).
? One or more U.N. International Agency for Research on Cancer (IARC) review lines
(Data Type V), regardless of whether the IARC review concluded that the
carcinogenicity of the substance was noted as Sufficient Evidence, Limited Evidence,
Inadequate Evidence, No Evidence, or (Evidence Suggesting Lack of Carcinogencity) .
? One or more National Toxicology Program (NTP) carcinogenesis bioassay studies status
lines (Data Type Y), regardless of whether the substance had only been selected for test
or whether the NTP study showed Clear Evidence, Some Evidence, Equivocal Evidence,
No Evidence, or Inadequate Study of Carcinogenicity, or that the test is still in progress.
Based on the above criteria, therefore, there may be some substances in RTECS速 that have only
negative IARC reviews or NTP status lines, but that still appear with the descriptor code
tumorigen.? This is done to bring the significance of the results of the IARC reviews and the
NTP studies to the users attention. Again, this points out the need to review the complete data
record before drawing any conclusion about the total toxic potential of a substance. The user must
not rely solely on the descriptor code.
Any substance with the descriptor code Reproductive Effector? will contain:
? One or more reproductive effects data lines (Data Type R) or
? One or more tumorigenic data lines (Data Type S) that cite either transplacental
carcinogenesis (Toxic Effects Code [TEC] T65) or tumors to the reproductive system
(TEC T61, T62, T63, T64,or T69). Thus, a substance reported to cause these latter two
types of effects will contain both tumorigen and reproductive effector compound
descriptor codes.
Any substance with the descriptor code Mutagen? will contain one or more mutagenic data lines
(Data Type Q).
Any substance described as a Primary Irritant? will contain one or more skin or eye irritation data
lines (Data Type P) in its RTECS速 data record.
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The descriptor code Human Data? will access all 5 categories (human, man, woman, child,
infant).
Hum Human
Man Man
Wmn Woman
Chd Child
Inf Infant
The remaining five descriptor codes (Agricultural Chemical, Drug, Organometallic, Hormone, and
Natural Product) are use or application codes and are included in the file based only on
information found in the references cited in RTECS速. For example, if an article that reports an
oral-rat LD50 value for a substance indicates the substance is used as a drug or a pesticide, then it
will be so coded in the file. However, if the article makes no such indication, descriptor codes will
not be added to the data record. Therefore, the user should recognize that these classifications are
not all-inclusive; they are based solely on information in the references from which the RTECS速 is
compiled.
Agricultural chemicals include those used to improve crop yields, such as fertilizers and pesticides
of all kinds. Drugs include both commercially available (approved) compounds, as well as those
that have been identified as experimental. Organometallic includes organic compounds comprised
of a metal or metalloids attached directly to carbon. Hormones include both those naturally found
in the body and synthetic substances that act like hormones. Natural products include organic
compounds that are produced by plants, animals, and microorganisms and that are not
commercially synthesized.
10. Skin and Eye Irritation Data (Data Type P). Each irritation data line includes, in sequence, the
tissue tested (skin or eye); the species of animal tested; the total dose and where applicable, the
duration of exposure; for skin tests only, whether open or occlusive; an interpretation of the
irritation response severity when noted by the author; and the reference from which the
information was extracted. Only positive irritation test results are included in the Registry.
Substances that are applied topically to the skin or the mucous membranes can elicit either,
systemic effects of an acute or chronic nature, or local effects, more properly termed primary
irritation.? A primary irritant is a substance that, if present in sufficient quantity for a sufficient
period of time, will produce a non-allergic, inflammatory reaction of the skin or of the mucous
membrane at the site of contact. Primary irritants are further limited by the editor to those
substances that are not corrosive. Hence, concentrated sulfuric acid is not classified as a primary
irritant.
a.) Primary Skin Irritation. In experimental animals, a primary skin irritant is defined as a
chemical substance that produces an irritant response on first exposure in a majority of the test
subjects. However, in some instances compounds act more subtly and require either repeated
contact or special environmental conditions (humidity, temperature, occlusion, etc.) to produce a
response.
One of the standard animal irritation tests is the Draize procedure (Journal of Pharmacology and
Experimental Therapeutics, 82: 377-390, 1944). This procedure has been modified and adopted as
a regulatory test by the Consumer Product Safety Commission (CPSC) in 16 CFR 1500.41. In this
test a known amount (0.5 ml of a liquid or 0.5 gm of a solid or semisolid) of the test substance is
introduced under a one square inch gauze patch. The patch is applied to the skin (clipped free of
hair) of twelve albino rabbits. Six rabbits are tested with intact skin and six with abraded skin. The
abrasions are minor incisions made through the stratum corneum, but are not sufficiently deep to
disturb the dermis or produce bleeding. The patch is secured in place with adhesive tape, and the
entire trunk of the animal is wrapped with an impervious material, such as rubberized cloth, for a
24-hour period. The animal is immobilized during exposure. After 24 hours the patches are
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removed and the resulting reaction evaluated for erythema, eschar, and edema formation. The
reaction is again scored at the end of 72 hours (48 hours after the initial reading), and the two
readings are averaged. A substance producing any degree of positive reaction is cited in the
Registry as an irritant.
As the modified Draize procedure described above has become the standard test specified by the
U.S. Government, nearly all of the primary skin irritation data either strictly adhere to the test
protocol or involve only simple modifications to it. When test procedures other than those
described above are reported in the literature, appropriate codes are included in the irritation data
line to indicate those deviations.
The most common modification is the lack of occlusion of the test patch, so that the treated area is
left open to the atmosphere. In such cases, the notation open? appears in the irritation data line.
Another frequent modification involves whole arm or whole body immersion in the test substance
or, more commonly, in a dilute aqueous solution of the test substance. This type of test is often
conducted on soap or detergent solutions. Immersion data are identified by the abbreviation imm?
in the data line.
The dose reported is based first on the lowest dose producing an irritant effect and second on the
latest study published. The dose is expressed as follows:
? Single application by the modified Draize procedure is indicated by only a dose amount.
If no exposure time is given, then the data are for the standard 72-hour test. For test times
other than 72 hours, the dose data are given in mg (or in an appropriate unit)/duration of
exposure, e.g., 10mg/24H.
? Multiple applications involve administration of the dose in divided portions applied
periodically. The total dose of test substance is expressed in mg (or appropriate
unit)/duration of exposure, with the symbol I? indicating intermittent exposure, e.g.,
5mg/6D-I.
The method of testing substances for primary skin irritation given in the U.S. Code of Federal
Regulations (CFR) does not indicate an interpretation of the response. However, some authors do
include a subjective rating of the irritation observed. If such a severity rating is given, it is
included in the data line as mild (MLD?), moderate (MOD?), or severe (SEV?). The Draize
procedure employs a rating that is included here for informational purposes only since other
researchers may not categorize response in this manner.
Category Draize Code Skin Reaction
Mild MLD Well defined erythema and slight edema (edges of
area well defined by definite raising)
Moderate MOD Moderate to severe erythema and moderate edema
(area raised approximately 1 mm)
Severe SEV Severe erythema (beet redness) to slight eschar
formation (injuries in depth) and severe edema
(raised more than 1 mm and extending beyond area
of exposure)
b.) Primary Eye Irritation. In experimental animals, a primary eye irritant is defined as a
chemical substance that produces an irritant response in the test subject on first exposure. Eye
irritation study procedures developed by Draize have been modified and adopted as a regulatory
test by CPSC in 16 CFR 1500.42. In this procedure, a known amount of the test material (0.1 ml
of a liquid or 100 mg of a solid or paste) is placed in one eye of each of six albino rabbits; the
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other eye remains untreated, serving as a control. The eyes are not washed after instillation and are
examined at 24, 48, and 72 hours for ocular reaction. After the recording of ocular reaction at 24
hours, any or all eyes may be further examined, following the application of fluorescein. Any or
all of eyes may also be washed with a sodium chloride solution (U.S.P. or equivalent) after the 24-
hour reaction has been recorded.
A test is scored positive if any of the following effects are observed: (1) ulceration (besides fine
stippling); (2) opacity of the cornea (other than slight dulling of normal luster); (3) inflammation
of the iris (other than a slight deepening of the rugae or circumcorneal injection of the blood
vessel); (4) swelling of the conjunctiva (excluding the cornea and iris) with eversion of the eyelid;
or (5) a diffuse crimson-red color with individual vessels not clearly identifiable. A substance is an
eye irritant if four of six rabbits score positive. It is considered a nonirritant if none or only one of
six animals exhibits irritation. If intermediate results are obtained, the test is performed again. For
the purpose of RTECS速, substances producing any degree of irritation in the eye are identified in
the Registry as irritants. When an author has designated a substance as either a mild, moderate, or
severe eye irritant, this designation is also reported.
The dose reported is based first on the lowest dose producing an irritant effect and second on the
latest study published. Single and multiple applications are indicated as described in Section 10a
above. Test times other than 72 hours are noted in the dose. All eye irritant test exposures are
assumed to be continuous, unless the reference states that the eyes were washed after instillation.
In this case, the notation rns?(rinsed) is included in the data line.
c.) Species Exposed. Since Draize procedures for determining both skin and eye irritation
specify rabbits as the test species, most of the animal irritation data in the Registry are for rabbits,
although any of the species listed in Table V may be used. The editor endeavors to include as
much human data as possible since this information is directly applicable to occupational
exposure. Much of this data comes from studies conducted on volunteers (such as the cosmetic or
soap ingredients) or from persons accidentally exposed. When an accidental exposure, such as a
spill, is cited, the data line includes the abbreviation nse? (non-standard exposure). In these cases
it is often very difficult to determine the precise amount of the substance to which the individual
was exposed. Therefore, for accidental exposures an estimate of the concentration or the strength
of the substance, rather than a total dose amount, is generally provided.
11. Mutation Data (Data Type Q). Mutation data include both whole animal and in vitro studies. Each
mutation data line includes, in sequence, the mutation test system utilized, the species of tested
organism (and, where applicable, the route of administration or cell type), the exposure
concentration or dose, and the reference from which the information was extracted. Only positive
mutation test results are cited in the Registry.
A mutation is defined as any heritable change in genetic material. Unlike irritation, reproductive
effects, tumorigenic, acute, and other multiple dose toxicity data (see Sections 10, 12, 13, 14, and
15, respectively), which report the results of whole animal studies, mutation data also include
studies on lower organisms such as bacteria, yeasts, molds, and insects, as well as in vitro
mammalian cell cultures. Studies of plant mutagenesis are not now included in the Registry. No
attempt is made to evaluate the significance of the data or to rate the relative potency of the
compound as a mutagenic risk to man.
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a.) Mutation Test System. A number of test systems are used to detect genetic alterations
caused by chemical substances. Those systems currently cited in the Registry are listed below.
Others found in the literature have been grouped together under the general term other mutation
test system? (oms). Each test system is identified by the 3-letter code shown in parentheses. For
additional information about mutation tests, the reader may wish to consult the Handbook of
Mutagenicity Test Procedures, edited by B.J. Kilbey, M. Legator, W. Nichols, and C. Ramel
(Amsterdam: Elsevier, Second Edition, 1984).
? Mutation in Microorganisms (mmo) - System is based on the detection of heritable
genetic alterations in microorganisms exposed directly to the chemical substance. An
enzymatic activation step is automatically included in the test procedure. To differentiate
between early tests in which the activation step was not an automatic inclusion, the
notation with S9" or without S9" will appear on the dataline.
? Micronucleus Test (mnt) - System utilizes the fact that chromosomes or chromosome
fragments may not be incorporated into one or the other of the daughter nuclei during cell
division.
? Specific Locus Test (slt) - System utilizes a method for detecting and measuring rates of
mutation at any or all of several recessive loci.
? DNA Damage (dnd) - System detects the damage to DNA strands, including strand
breaks, crosslinks, and other abnormalities.
? DNA Repair (dnr) - System utilizes methods of monitoring DNA repair as a function of
induced genetic damage.
? Unscheduled DNA Synthesis (dns) - System detects the synthesis of DNA during usually
non-synthetic phases.
? DNA Inhibition (dni) - System detects inhibition of DNA synthesis.
? Gene Conversion and Mitotic Recombination (mrc) - System utilizes unequal recovery of
genetic markers in the region of the exchange during genetic recombination.
? Cytogenetic Analysis (cyt) - System utilizes cultured cells or cell lines to assay for
chromosomal aberrations following the administration of chemical substances.
? Sister Chromatid Exchange (sce) - System detects the interchange of DNA in cytological
preparations of metaphase chromosomes between replication products at apparently
homologous loci.
? Sex Chromosome Loss and Nondisjunction (sln) - System measures the non-separation of
homologous chromosomes at meiosis and mitosis.
? Dominant Lethal Test (dlt) - A dominant lethal is a genetic change in a gamete that kills
the zygote produced by that gamete. In mammals, the dominant lethal test measures the
reduction of litter size by examining the uterus and noting the number of surviving and
dead implants.
? Mutation in Mammalian Somatic Cells (msc) - System utilizes the induction and isolation
of mutants in cultured mammalian cells by identification of the gene change.
? Host-Mediated Assay (hma) - System uses two separate species, generally mammalian
and bacterial, to detect heritable genetic alteration caused by metabolic conversion of
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Comprehensive Guide to RTECS
chemical substances administered to host mammalian species in the bacterial indicator
species.
? Sperm Morphology (spm) - System measures the departure from normal in the
appearance of sperm.
? Heritable Translocation Test (trn) - Test measures the transmissibility of induced
translocations to subsequent generations. In mammals, the test uses sterility and reduced
fertility in the progeny of the treated parent. In addition, cytological analysis of the F1
progeny or subsequent progeny of the treated parent is carried out to prove the existence
of the induced translocation. In Drosophila, heritable translocations are detected
genetically using easily distinguishable phenotypic markers, and these translocations can
be verified with cytogenetic techniques.
? Morphological Transformation (mtr) - System utilizes morphological criteria to detect
cytological differences between normal and transformed tumorigenic cells.
? Phage Inhibition Capacity (pic) - System utilizes a lysogenic virus to detect a change in
the genetic characteristics by the transformation of the virus from noninfectious to
infectious.
? Body Fluid Assay (bfa) - System uses two separate species, usually mammalian and
bacterial. Test substance is first administered to host, from whom body fluid (e.g., blood
or urine) is subsequently taken. This body fluid is then tested in vitro, and mutations are
measured in the bacterial species.
? DNA Adduct (dna) - System detects the covalent bonding of chemical substances to
DNA through the identification of modified nucleotides.
b.) Test Species. Those test species that are peculiar to mutation data cited in the Registry are
designated by the 3-letter codes shown in the following table. Other species are listed in Table
I.
Code Species
Bacteria: bcs Bacillus subtilis
esc Escherichia coli
hmi Haemophilus influenzae
klp Klebsiella pneumoniae
sat Salmonella typhimurium
srm Serratia marcescens
Molds: asn Aspergillus nidulans
nsc Neurospora crassa
Yeasts: smc Saccharomyces cerevisiae
ssp Schizosaccharomyces pombe
Protozoa: clr Chylamydomonas reinhardi
eug Euglena gracilis
omi Other microorganisms
Insects: dmg Drosophila melanogaster
dpo Drosophila pseudo-obscura
grh Grasshopper
slw Silkworm
oin Other insect
Fish: sal Salmon
ofs Other fish
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December 2007
If the test organism is a cell type from a particular species (generally mammalian), the parent
species is reported, followed by a colon and the cell type designation. For example, human
leukocytes are coded hmn:leu.? The various cell types currently cited in the Registry are listed in
the following table:
Designation Cell Type
Ast Ascites tumor
Bmr Bone marrow
Emb Embryo
Fbr Fibroblast
Hla HeLa cell
Kdy Kidney
Leu Leukocyte
Lng Lung
Lvr Liver
Lym Lymphocyte
Mmr Mammary gland
Ovr Ovary
Spr Sperm
Tes Testis
Oth Other cell types not
listed above
In the case of host-mediated and body fluid assays, the host and indicator organisms are given as
follows: host organism/indicator organism, e.g., ham/sat? for a test in which hamsters were
exposed to the test chemical and S. Typhimurium was used as the indicator organism.
For in vivo mutagenic studies, the route of administration is specified following the species
designation, e.g., mus-orl? for oral administration to mice. See Table IV for a complete list of
routes cited in the Registry. The route of administration is not specified for in vitro data.
c.) Units of Exposure. The lowest dose producing a positive effect is cited. The authors
calculations are used to determine the lowest dose at which a positive effect was observed. If the
author fails to state the lowest effective dose, two times the control dose will be used. Ideally, the
dose should be reported in universally accepted toxicological units such as milligrams of test
chemical per kilogram of test animal body weight. While this is possible when the actual intake of
a chemical by an organism of known weight is reported, it is not possible in many systems using
insect and bacterial species. When a dose is reported or where the amount can be converted to a
dose unit, it is normally listed as milligrams per kilogram (mg/kg). However, grams (gm),
micrograms (ug), nanograms (ng), or picograms (pg) per kilogram may also be used for
convenience of presentation. Concentrations of gaseous substances in air are listed as parts per
hundred (pph), million (ppm), billion (ppb), or trillion (ppt).
Test systems using microbial organisms usually report exposure data as an amount of chemical per
liter (L), or amount per plate, well, or disc. The amount may be on a weight (gm, mg, ug, ng, or
pg) or molar (millimole [mmol], micromole [umole], nanomole [nmole], or picomole [pmole])
basis. These units describe the exposure concentration rather than the dose actually taken up by the
test species. Insufficient data currently exists to permit the development of dose amounts from this
information. In such cases, therefore, the substance concentration units used by the author are
reported.
Since the exposure values reported in host-mediated assays are the doses delivered to the host
organism, no attempt is made to estimate the exposure concentration to the indicator organism.
The exposure values cited for host-mediated assay data are in units of milligrams (or other
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appropriate unit of weight) of substance administered per kilogram of host body weight or in parts
of vapor or gas per million (ppm) parts of air (or other appropriate concentration) by volume.
12. Reproductive Effects Data (Data Type R). Each reproductive effects data line includes, in
sequence, the reproductive effects code(s), the route of exposure, the species of animal tested, the
type of dose, the total dose amount administered, the time and duration of administration, and the
reference from which the information was extracted. Only positive reproductive effects data for
mammalian species are cited in the Registry. Because of differences in the reproductive systems
among species and the systems? varying responses to chemical exposures, no attempt is made to
extrapolate animal data or to evaluate the significance of a substance as a reproductive risk to
humans. Each element of the reproductive effects data line is discussed below:
a.) Reproductive Effects Code. For purposes of the Registry, the reproductive effects for which
dose data are cited have been grouped into seven categories (see Table III): paternal effects,
maternal effects, effects on fertility, effects on the embryo or fetus, specific developmental
abnormalities, tumorigenic effects, and effects on the newborn. Within these seven categories,
specific effects have been defined. The effects cited on a given data line were reported to occur in
the species and at the dose level given on that line. Up to three reproductive effects are cited on a
single data line. If more than three reproductive effects are reported for the same route-species-
dose level-duration combination, duplicate lines will appear in this section of the file to allow
complete coding of the reproductive effects.
b.) Route of Exposure or Administration. See Table IV for a complete list of abbreviations and
definitions of the various routes of exposure reported in the Registry. For reproductive effects
data, the specific route is listed in RTECS速 either when the substance was administered to only
one of the parents or when the substance was administered to both parents by the same route.
However, if the substance was administered to each parent by a different route, the route is
indicated as mul? (multiple).
c.) Species Exposed. Reproductive effects data are cited in the Registry for mammalian species
only. Species abbreviations are the same as those used for acute toxicity data and are shown in
Table V. Also shown in Table V are approximate gestation periods.
d.) Type of Exposure. Only two types of exposure, TDLo and TCLo, are used to describe the
dose amounts reported for reproductive effects data. These two terms, which are also used to
describe toxic dose data, are defined in Section14d.
e.) Dose Amounts and Units. The total dose amount that was administered to the exposed
parent is given. If the substance was administered to both parents, the individual amounts to each
parent are added together and the total amount shown. Where necessary, appropriate conversion of
dose units is made. The dose amounts listed are those for which the reported effects are
statistically significant. The statistical test is that used by the author. If no statistic is reported, a
Fishers Exact Test is applied with significance at the 0.05 level, unless the author makes a strong
case for significance at some other level.
Dose units are usually given as an amount administered per unit body weight or as parts of vapor
or gas per million parts of air by volume. A complete description of dose units is given in Section
14e. There is no limitation on either the quantity or concentration of the dose or the duration of
exposure reported to have caused the reproductive effect.
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December 2007
f.) Time and Duration of Treatment. The time when a substance is administered to either or
both parents may significantly affect the results of a reproductive study, because there are
differing critical periods during the reproductive cycles of each species. Therefore, to provide
some indication of when the substance was administered, which should facilitate selection of
specific data for analysis by the reader, a series of up to four terms follows the dose amount. These
terms indicate to which parent(s) and at what time the substance was administered. The terms take
the general form:
(uD male/vD pre/w-xD preg/yD post)
where u = total number of days of administration to male prior to mating
v = total number of days of administration to female prior to mating
w = first day of administration to pregnant female during gestation
x = last day of administration to pregnant female during gestation
y = total number of days of administration to lactating mother after
birth of offspring
If administration is to the male only, then only the first of the above four terms is shown following
the total dose to the male, e.g., 10 mg/kg (5D male). If administration is to the female only, then
only the second, third, or fourth term, or any combination thereof, is shown following the total
dose to the female. For example:
10 mg/kg (3D pre)
10 mg/kg (3D pre/4-7D preg)
10 mg/kg (3D pr/4-7D per/5D post)
10 mg/kg (3D pre/5D post)10 mg/kg (4-7D preg)
10 mg/kg (4-7D preg/5D post)
10 mg/kg (5D post) (NOTE: This example indicates administration to the
lactating mother only after birth of the offspring.)
If the administration is to both parents, then the first term and any combination of the last three
terms are listed, e.g., 10 mg/kg (5D male/3D preg/4-7D post). If administration is continuous
through two or more of the above periods, the above format is abbreviated by replacing the slash
(/) with a dash (-). For example, 10 mg/kg (3D pre-5D post) means a total of 10 mg/kg
administered to the female for three days prior to mating, on each day during gestation, and for
five days following birth. Approximate gestation period for various species are shown in Table V.
g.) Multi-generation Studies. Some reproductive studies entail administration of a substance to
several consecutive generations, with the reproductive effects measured in the final generation.
The protocols for such studies vary widely. Therefore, because of the inherent complexity and
variability of these studies, they are cited in RTECS速 in a simplified format as follows:
The specific route of administration is reported if it was the same for all parents of all generations;
otherwise, the abbreviation mul? is used. The total dose amount shown is that administered to the
F0 generation only (as described in Section 12e above); doses to the Fn (where n = 1,2,3, etc.)
generations are not reported. The time and duration of treatment for multi-generation studies are
not included in the data line. Instead, the dose amount is followed by multi-generation, e.g., 10
mg/kg multi-generation. The reader must consult the cited reference for complete details of the
study protocol.
13. Tumorigenic Data (Data Type S). Tumorigenic dose data also appears under Data Type R?. The
format of these data types are identical to that of the acute toxicity data line, which is described in
detail in Section 14. Briefly, each tumorigenic data line sequentially includes toxic effects code(s),
the route of exposure, the species of animal studied, the type of dose (either TDLo or TCLo), the
total dose amount administered, the duration of exposure, and the reference from which the
information was extracted. Only positive or equivocal tumorigenic reports are cited in this section.
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Comprehensive Guide to RTECS
For other information about tumorigenicity, the reader should see the IARC monograph review
lines (Section 17b), the ACGIH review lines (Section 17a), and the NTP status lines (Section 20d).
The importance attached to reports of the carcinogenic activity of substances necessitates a more
detailed discussion of the criteria used to include this type of data in the Registry. Tumorigenic
citations are classified according to the reported results of the study only to aid the reader in
selecting appropriate references for in-depth review and evaluation. Two classifications used are
V01, indicating a positive carcinogenic finding, and V02, indicating a study producing benign
tumors. A third classification, V03, denotes those studies reporting uncertain, but seemingly
positive, results. The criteria for these three classifications are listed below. These criteria are used
to abstract the data in individual reports on a consistent basis and do not represent a
comprehensive evaluation of the tumorigenic potential of a substance to humans.
The Registry cites multiple studies in which tumorigenic responses were reported. That is, for a
given substance, a particular route-species combination may be cited more than once if the results
of the multiple studies are coded V01, V02, or V03. These multiple tumorigenic entries have been
cited simply with a toxicity measure of TD (toxic dose) or TC (toxic concentration).
The following nine technical criteria are used by RTECS速 to abstract the toxicological literature
and classify studies that report positive tumorigenic responses. NO ATTEMPTS ARE MADE
EITHER TO EVALUATE THE VARIOUS TEST PROCEDURES OR TO CORRELATE
RESULTS FROM DIFFERENT EXPERIMENTS.
(a) A citation is coded with the TEC V01? (Carcinogenic by RTECS criteria) when review of
a study reveals that all of the following criteria are satisfied:
? A statistically significant increase in the incidence of tumors in the test animals. The
statistical test used is that used by the author. If no statistic is reported, a Fishers Exact
Test is applied with significance at the 0.05 level, unless the author makes a strong case
for significance at some other level.
? A control group of animals is used and the treated and control animals are maintained
under identical conditions.
? The sole experimental variable between the groups is the administration or non-
administration of the test substance (see i below).
? The tumors consist of autonomous populations of cells of abnormal cytology capable of
invading and destroying normal tissues, or the tumors metastasize as confirmed by
histopathology.
(b) A citation is coded with the TEC V02? (Neoplastic by RTECS criteria) when review of a
study reveals that all of the following criteria are satisfied:
? A statistically significant increase in the incidence of tumors in the test animals. The
statistical test used is that used by the author. If no statistic is reported, a Fishers Exact
Test is applied with significance at the 0.05 level, unless the author makes a strong case
for significance at some other level.
? A control group of animals is used, and the treated and control animals are maintained
under identical conditions.
? The sole experimental variable between the groups is the administration or non-
administration of the test substance (see i below).
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December 2007
? The tumors consist of cells that closely resemble the tissue of origin, that are not grossly
abnormal cytologically, that may compress surrounding tissues, but that neither invade
tissues nor metastasize; or
? The tumors produced cannot definitely be classified as either benign or malignant.
(c) A citation is coded with the TEC V03? (Equivocal tumorigenic agent by RTECS criteria)
when some evidence of tumorigenic activity is presented, but one or more of the criteria listed in
(a) or (b) above is lacking. Thus, a report with positive pathological findings, but with no mention
of control animals, is coded V03. Reports in which the results are not interpretable are not cited in
the Registry.
(d) Since an author may make statements or conclusions based on a larger context than that of
the particular data reported, papers in which the authors conclusions differ substantially from the
evidence presented in the paper are subject to review by the RTECS速 Editorial Review Board.
All doses except for those for transplacental carcinogenesis are reported in RTECS速 in one
(e)
of the following formats.
? For all routes of administration other than inhalation: Cumulative dose in mg (or other
appropriate unit)/kg/duration of administration.
Whenever the dose reported in the reference is not in the above units, conversion to this
format is made based on the information given in Section 14e. The total cumulative dose
is derived from the lowest dose level that produces tumors in the test group.
? For inhalation experiments: Concentrations in ppm (or mg/m3 )/total duration of exposure.
The concentration refers to the lowest concentration that produces tumors.
Transplacental carcinogenic doses are reported in RTECS速 in one of the following formats:
(f)
? For all routes of administration other than inhalation: Cumulative dose in mg/kg/(time of
administration during pregnancy). The cumulative dose is derived from the lowest single
dose that produces tumors in the offspring. The chemical is administered to the mother.
? For inhalation experiments: Concentration in ppm (or mg/m3 )/(time of exposure during
pregnancy).The concentration refers to the lowest concentration that produces tumors in
the offspring. The mother is exposed to the chemical either during pregnancy or lactation.
For the purposes of RTECS速, all test chemicals are reported as pure, unless otherwise stated
(g)
by the author. This does not rule out the possibility that unknown impurities may have been
present.
(h) A mixture of compounds whose test results satisfy the criteria in (a), (b), or (c) above is
included if the composition of the mixture can be clearly defined.
(i) For tests involving promoters or initiators, a study is included if the following conditions
are satisfied (in addition to the criteria in (a), (b), or (c) above:
? The test chemical is applied first followed by an application of a standard promoter. A
positive control group in which the test animals are subjected to the same standard
promoter under identical conditions is maintained throughout the duration of the
experiment. The data are not used if no mention of positive and negative control groups is
made in the reference.
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Comprehensive Guide to RTECS
? A known carcinogen is first applied as an initiator, followed by application of the test
chemical as a promoter. A positive control group in which the test animals are subjected
to the same initiator under identical conditions is maintained throughout the duration of
the experiment. The data are not used if no mention of positive and negative control
groups is made in the reference.
14. Acute Toxicity Data (Data Type T). Each dose data line sequentially includes toxic effects; the
route of exposure; the species of animal studied; the type of dose; the amount of substance per
body weight or concentration per unit of air volume and, where applicable, the duration of
exposure; and the reference from which the information was extracted. Each element of the acute
toxicity line is discussed below.
a.) Toxic Effects. The toxic effects listed in the Registry should not be viewed as an exhaustive
representation of all the potential toxic effects of a compound. These effects are noted in the
Registry by means of an alphanumeric Toxic Effects Code (TEC). The TEC permits a detailed
coding of the toxic effects reported in the literature and is included for human and animal data.
In the database, the TEC is the first entry on the toxicity data line; it appears to the left of the route
of administration. Each TEC is made up of one or more code segments, each of which contains
three characters. Each TEC, which may contain as many as three code segments, is preceded by a
single digit (1, 2, or 3) that indicates the number of segments. For example, the entry ?2J18K13?
indicates two code segments: J18 and K13. An explanation of the individual code segments is
given below.
The first position of each segment is alphabetic and describes an organ, tissue or functional
system, or other major physiological or behavioral grouping. Positions two and three are numeric
damage codes that specify individual toxic effects within each system. A complete list of TECs,
including all major system groupings and individual damage codes, appears in Table II. Using
Table II to decode the preceding example (2J18K13), the reader finds that for the J18? TEC
segment, the J? represents the lung as the affected organ and the ?18" indicates pleural
thickening. For K13,? K? represents the gastrointestinal system and ?13? means nausea or
vomiting.
In using the TEC, the reader should be aware of the following restrictions:
? TECs listed in each line describe effects reported only for the route and species specified
on that line.
? The TECs listed in the Registry should not be viewed as an exhaustive representation of
all the potential toxic effects of a compound. This caution results from two
considerations. The first is that a maximum of three code segments is reported for each
RTECS速 data line. For studies in which more than three effects were reported, only those
deemed most significant will be listed. Second, the effects are limited to those that meet
the basic selection criteria for inclusion in the Registry, i.e., lowest dose for a given
route-species combination. Studies done to determine acute LD50 values often report
little other information besides the LD50 itself.
b.) Route of Exposure or Administration. Although many exposures to substances in the
industrial community occur via the respiratory tract or skin, most studies in the published literature
report exposures of experimental animals in which the test substances were introduced primarily
through the mouth by pills, in food, in drinking water, or by intubation directly into the stomach.
The abbreviations and definitions of the various routes of exposure reported in the Registry are
found in Table IV.
c.) Species Exposed. Since the effects of exposure of humans are of primary concern, we have
indicated, when available, whether the results were observed in man, woman, child, or infant. If no
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December 2007
such distinction was made in the reference, the abbreviation hmn? (human) is used. (NOTE: it is
also possible to search out all human data by using the Compound Descriptor Code P? for human
data). However, the results of studies on rats or mice are the most frequently reported and hence
provide the most useful data for comparative purposes. The species and abbreviations used in
reporting toxic dose data are listed alphabetically in Table I.
d.) Description of Exposure. Six abbreviations are used to describe the administered dose
reported in the literature. These abbreviations indicate whether the dose caused death (LD) or
other toxic non-lethal effect (TD), or whether it was administered as a lethal concentration (LC) or
toxic concentration (TC) in the inhaled air. In general, the term Lo? is used where the number of
subjects studied was not a significant number from the population or the calculated percentage of
subjects showing an effect was 100. The doses and concentrations are defined as follows:
TDLo--Toxic Dose Low--The lowest dose of a substance introduced by any route, other than
inhalation, over any given period of time and reported to produce any toxic effect in humans or
animals, or to produce tumorigenic, reproductive, or multiple dose effects in animals.
TCLo--Toxic Concentration Low--The lowest concentration of a substance in air to which humans
or animals have been exposed for any given period of time that has produced any toxic effect in
humans or animals, or produced tumorigenic, reproductive, or multiple dose effects in animals.
LDLo--Lethal Dose Low--The lowest dose (other than LD50) of a substance introduced by any
route, other than inhalation, over any given period of time in one or more divided portions and
reported to have caused death in humans or animals.
LD50--Lethal Dose Fifty--A calculated dose of a substance which is expected to cause the death
of 50% of an entire defined experimental animal population. It is determined from the exposure to
the substance by any route other than inhalation of a significant number from that population.
Other lethal dose percentages, such as LD1, LD10, LD30, and LD99, may be published in the
scientific literature for the specific purposes of the author. Such data would be published in the
Registry if these figures, in the absence of a calculated lethal dose (LD50), were the lowest found
in the literature.
LCLo--Lethal Concentration Low--The lowest concentration of a substance in air, other than
LC50, which has been reported to have caused death in humans or animals. The reported
concentrations may be entered for periods of exposure that are less than 24 hours (acute) or greater
than 24 hours (subacute and chronic).
LC50--Lethal Concentration Fifty--A calculated concentration of substance in air, exposure to
which for a specified length of time is expected to cause the death of 50% of an entire defined
experimental animal population. It is determined from the exposure to the substance of a
significant number from that population.
e.) Units of Dose Measurement. As in almost all experimental toxicology, the doses given are
expressed in terms of the quantity administered per unit body weight, or quantity per skin surface
area, or quantity per unit volume of the respired air. In addition, the duration of time over which
the dose was administered is also listed, as needed.
Dose amounts are generally expressed as milligrams (one thousandth of a gram) per kilogram
(mg/kg). In some cases, because of dose size and its practical presentation in the file, micrograms
(one millionth of a gram) per kilogram (ug/kg), or nanograms (one billionth of a gram) per
kilogram (ng/kg) are used. Volume measurements of dose were converted to weight units by
appropriate calculations. Densities were obtained from standard reference texts. Where densities
were not readily available, doses were reported as milliliters per kilogram (ml/kg).
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Comprehensive Guide to RTECS
All body weights are converted to kilograms (kg) for uniformity. For those references in which the
dose was reported to have been administered to an animal of unspecified weight or a given number
of animals in a group (e.g., feeding studies) without weight data, the weights of the respective
animal species are assumed to be those listed in Table V and the dose listed on a per kilogram
body weight basis. Assumptions for daily food and water intake are found in Table V to allow
approximating dosages for humans and experimental animals where the dose was originally
reported as a concentration in food or water. The values presented are selections which are
reasonable for the species and convenient for dose calculations.
Concentrations of a gaseous substance in air are generally listed as parts of vapor or gas per
million parts of air by volume (ppm). However, parts per hundred (pph or percent), parts per
billion (ppb), or parts per trillion (ppt) may be used for convenience of presentation. If the
substance is a solid or a liquid, the concentrations are listed preferably as milligrams per cubic
meter (mg/m3 ), but may, as applicable, be listed as micrograms per cubic meter (ug/m3 ),
nanograms per cubic meter (ng/m3), or picograms per cubic meter (pg/m3) of air. For those cases in
which other measurements of contaminants are used, such as the number of fibers or particles, the
measurement is spelled out.
f.) Duration of Exposure. The duration of exposure is included to give an indication of the
testing period during which the human or animal was exposed to the total dose.
Where the duration of exposure is available, time is presented as minutes (M), hours (H), days (D),
weeks (W), or years (Y). Additionally, continuous (C) indicates that the exposure was continuous
over the time administered, such as ad libitum feeding studies or 24-hour, 7-day per week
inhalation exposures. Intermittent (I) indicates that the dose was administered during discrete
periods, such as daily, twice weekly, etc. In all cases, the total duration of exposure appears first
after the kilogram body weight and slash, followed by descriptive data; e.g., 10 mg/kg/3W-I
means ten milligrams per kilogram body weight administered over a period of three weeks,
intermittently in a number of separate, discrete doses. This description is intended to provide the
reader with enough information for an approximation of the experimental conditions, which can be
further clarified by studying the reference cited.
g.) Frequency of Exposure. Frequency of exposure to the test substance varies depending on
the nature of the experiment. For the purposes of the Registry, frequency of exposure is given for
inhalation experiments, for human exposures (where applicable), or where reproductive,
tumorigenic, or other multiple dose data are specified (see Sections 12, 13, and 15 respectively).
15. Other Multiple Dose Toxicity Data (Data Type U). Citations in this field include the results of
multiple dose toxicity studies, of variable duration, which relate to other than mutagenic,
reproductive, or tumorigenic effects. The format is similar to that found in the tumorigenic effects
data field, where toxic rather than lethal doses are indicated, including duration of exposure. The
numerical dose data is a cumulative amount over the duration of the study. The most common
study designs include thirteen week, twenty-six week, fifty-two week, and two year studies.
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December 2007
Toxicity Data Summary
Shown below is a summary of the several categories of toxicity data entries (Sections 12-15),
where they appear in the file, and how they are used.
Toxic Data Type
Exposure Regime Route of Exposure Human Animal
LD50 Single dose All except Not applicable Acute lethality (data type T)
inhalation statistically determined
LC50 Single dose Inhalation Not applicable Acute lethality (data type T)
statistically determined
LDLo Single dose All except Data type T Acute lethality (data type T)
(except for human inhalation
data)
LCLo Single dose Inhalation Data type T Acute lethality (data type T)
(except for human
data)
LD Single dose All except Not applicable Acute lethality (data type T)
inhalation lethal dose > dose reported
LC Single dose Inhalation Not applicable Acute lethality (data type T)
lethal dose > dose reported
TDLo Single or multiple All except All non-lethal Non-lethal (data types R, S,
dose inhalation (data types R, T, U)
S, T, U)
TCLo Single or multiple Inhalation All non-lethal Non-lethal (data types R, S,
dose (data types R, T, U)
S, T, U)
TD Single or multiple All except Not applicable Tumorigenic (data type S)
dose inhalation
TC Single or multiple Inhalation Not applicable Tumorigenic (data type S)
dose
16. Cited References. All references cited are publicly available. No government classified
documents have been used for source information. All references have been given a unique six-
letter CODEN character code (derived from the American Society for Testing and Materials
CODEN for Periodical Titles,? which identifies periodicals, serial publications, and individual
published works). For example, CNREA8? is the CODEN for Cancer Research, and PCBPBS?
for Pesticide Biochemistry and Physiology. For those references for which no CODEN was found,
the corresponding six-letter codes includes asterisks (*) in the last one or two positions, following
the first four or five letters of the acronym for the publication title. Following the CODEN
designation (for most entries) is the number of the volume, followed by a comma; the page
number of the first page of the article, followed by a comma; and a four-digit number, indicating
the year of publication. When the cited reference is a report, the report number is listed. Where
contributors have provided information on their unpublished studies, the CODEN consists of the
first three letters of the last name, the initials of the first and middle names, and a number sign (#).
The date of the letter supplying the information is listed. All CODEN acronyms are listed in
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Comprehensive Guide to RTECS
alphabetical order and defined in the CODEN Master File, (coden.del). The format of this file is
as follows:
Field Number Field Name Position Description
1 CODEN 1?6 Alphanumeric
2 Line Number 7?8 Numeric
3 Bibliographic Data 12 ? 105 Alphanumeric
17. Reviews (Data Type V). Three types of reviews are listed: (1) Threshold Limit Values (TLVs 速 ),
which are limits proposed by the American Conference of Governmental Industrial Hygienists
(ACGIH速); (2) International Agency for Research on Cancer (IARC) monograph reviews, which
are published by the United Nations, World Health Organization (WHO); and (3) general
toxicology review articles.
a.) Threshold Limit Value (TLVs速 ). The TLV速 is an ACGIH速 guideline and refers to the
airborne concentration of a substance to which nearly all workers may be repeatedly exposed, day
after day, over a working lifetime, without adverse health effects. The TLVs速 may be expressed as
a time-weighted average (TWA), as a short-term exposure limit (STEL), or as a ceiling value
(CL). The TWA is for a normal 8-hour workday or 40-hour work week. The STEL is the
maximum concentration to which workers can be exposed for up to 15 minutes, provided no more
than four excursions per day are permitted with at least 60 minutes between exposure periods and
provided the daily TWA is not also exceeded. The CL is the concentration that should not be
exceeded during any part of the working exposure. The notation ?(skin)? refers to a potential
significant contribution to the overall exposure by cutaneous routes, even though the airborne
exposures are at or below the TLV.
A separate TLV速 review line is included for those substances that ACGIH速 has developed a
carcinogen classification;
Confirmed Human Carcinogen (A1)
Suspected Human Carcinogen (A2)
Confirmed Animal Carcinogen with Unknown Relevance to Humans (A3)
Not Classifiable as a Human Carcinogen (A4)
Not Suspected as a Human Carcinogen (A5).
The TLVs速 can be found in the ? The Documentation of the Threshold Limit Values and
Biological Exposure Indices?. Copies of the complete TLVs速 Documentation may be ordered
from:
ACGIH速
1330 Kemper Meadow Drive
Cincinnati, Ohio 45240
Telephone (513) 742-2020, FAX (513) 742-3355.
The reader is cautioned that the TLVs速 are revised periodically. A Notice of Intended Changes?
for substances for which either a TLV速 is proposed for the first time or for which a change to an
existing TLV速 is proposed is published annually by ACGIH速. Proposed changes are considered
trial limits for two years, after which they are considered for inclusion as adopted TLVs速. Only
substances for which TLVs速 have been adopted and final documentation prepared are cited in the
Registry.
In addition, some TLVs速 are recommended for classes of substances rather than for individual
compounds. These classes may be based on certain chemical or physical properties, such as
solubility, that have not been determined for all potential members of the class. This makes it
difficult to cite individual substances belonging to the class. Any questions about the TLV速
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December 2007
citations in the Registry should be directed to ACGIH速. Any errors should be brought to the
attention of the RTECS速 Editor at the address given in the Introduction.
b.) IARC Cancer Reviews. In the United Nations International Agency for Research on Cancer
(IARC) monographs, information on suspected environmental carcinogens are examined, and
summaries of available data with appropriate references are presented. Included in these reviews
are synonyms, physical and chemical properties, uses and occurrence, and biological data relevant
to the evaluation of carcinogenic risk to humans.
The RTECS速 entry IARC CANCER REVIEW? indicates that some carcinogenicity data
pertaining to a compound has been reviewed by an IARC Working Group. The Registry
summarizes the Working Groups conclusion.
The IARC program of evaluation of carcinogenic risks to humans has evolved over the years since
it began in 1969. The IARC classification entered into the Registry is applicable for the volume
reviewed.
Monographs 1-42 published between 1971-1987, and Supplement 7: Overall Evaluations of
Carcinogenicity: An updating of the IARC Monographs Volumes 1 to 42?, published in 1987, are
described below.
The evidence of carcinogenicity in experimental animals was assessed by the Working Group and
judged to fall into one of four groups defined as follows:
? SUFFICIENT EVIDENCE of carcinogenicity is provided when there is an increased
incidence of malignant tumors: (a) in multiple species or strains; or (b) in multiple
experiments (preferably with different routes of administration or using different dose
levels); or (c) to an unusual degree with regard to the incidence, site or type of tumor, or
age at onset. Additional evidence may be provided by data on dose-response effects.
? LIMITED EVIDENCE of carcinogenicity is available when the data suggest a
carcinogenic effect but are limited because (a) the studies involve a single species, strain,
or experiment; (b) the experiments are restricted by inadequate dosage levels, inadequate
duration of exposure to the agent, inadequate period of follow-up, poor survival, too few
animals, or inadequate reporting; or (c) the neoplasms produced often occur
spontaneously, and in the past, have been difficult to classify as malignant by histological
criteria alone (e.g., lung adenomas and adenocarcinomas, and liver tumors in certain
strains of mice).
? INADEQUATE EVIDENCE is available when, because of major qualitative or
quantitative limitations, the studies cannot be interpreted as showing either the presence
or absence of a carcinogenic effect.
? NO EVIDENCE applies when several adequate studies are available which show that
within the limitations of the tests used, the chemical is not carcinogenic.
It should be noted that the categories SUFFICIENT EVIDENCE and LIMITED EVIDENCE refer
only to the strength of the experimental evidence that these chemicals are carcinogenic and not to
the extent of their carcinogenic activity, nor to the mechanism involved. The classification of any
chemical may change as new information becomes available.
The evidence for carcinogenicity from studies in humans was assessed by the Working Group and
judged to fall into one of four groups defined as follows:
? SUFFICIENT EVIDENCE of carcinogenicity indicates that there is a causal relationship
between the exposure and human cancer.
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Comprehensive Guide to RTECS
? LIMITED EVIDENCE of carcinogenicity indicates that a causal relationship is credible,
but that alternative explanations, such as chance, bias, or confounding, could not
adequately be excluded.
? INADEQUATE EVIDENCE, which applies to both positive and negative evidence,
indicated that one of two conditions prevailed: (a) there are few pertinent data; or (b) the
available studies, while showing evidence of association, do not exclude chance, bias, or
confounding.
? NO EVIDENCE applies when several adequate studies are available which do not show
evidence of carcinogenicity.
Monographs beginning with Volume 43 and beyond are classified as below.
The evidence relevant to carcinogenicity in experimental animals is classified into one of the
following categories:
? SUFFICIENT EVIDENCE of carcinogenicity: The Working Group considers that a
causal relationship has been established between the agent and an increased incidence
of malignant neoplasms or of an appropriate combination of benign and malignant
neoplasms in (a) two or more species of animals or (b) in two or more independent
studies in one species carried out at different times or in different laboratories or under
different protocols.
Exceptionally, a single study in one species might be considered to provide sufficient
evidence of carcinogenicity when malignant neoplasms occur to an unusual degree
with regard to incidence, site, type of tumor or age at onset.
? LIMITED EVIDENCE of carcinogenicity: The data suggest a carcinogenic effect but
are limited for making a definitive evaluation because, e.g. (a) the evidence of
carcinogenicity is restricted to a single experiment; or (b) there are unresolved
questions regarding the adequacy of the design, conduct or interpretation of the study;
or (c) the agent increased the incidence only of benign neoplasms or lesions of
uncertain neoplastic potential, or of certain neoplasms which may occur spontaneously
in high incidences in certain strains.
? INADEQUATE EVIDENCE of carcinogenicity: The studies cannot be interpreted as
showing either the presence or absence of a carcinogenic effect because of major
qualitative or quantitative limitations, or no data on cancer in experimental animals are
available.
? EVIDENCE SUGGESTING LACK OF CARCINOGENICITY: Adequate studies
involving at least two species are available which show that, within the limits of the
tests used, the agent is not carcinogenic. A conclusion of evidence suggesting lack of
carcinogenicity is inevitably limited to the species, tumor sites and levels of exposure
studied.
The evidence relevant to carcinogenicity from studies in humans is classified into one of the
following categories:
? SUFFICIENT EVIDENCE of carcinogenicity: The Working Group considers that a
causal relationship has been established between the agent and human cancer. That
is, a positive relationship has been observed between the exposure and cancer in
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December 2007
studies in which change, bias and confounding could be ruled out with reasonable
confidence.
? LIMITED EVIDENCE of carcinogenicity: A positive association has been observed
between the agent and cancer for which a causal interpretation is considered by the
Working Group to be credible, but chance, bias or confounding could not be ruled
out with reasonable confidence.
? INADEQUATE EVIDENCE of carcinogenicity: The available studies are of
insufficient quality, consistency or statistical power to permit a conclusion regarding
the presence or absence of a causal association between exposure and cancer, or no
data on cancer in humans are available.
? EVIDENCE SUGGESTING LACK OF CARCINOGENICITY: There are several
adequate studies covering the full range of levels of exposure that human beings are
known to encounter, which are mutually consistent in not showing a positive
association between exposure to the agent and any studied cancer at any observed
level of exposure. A conclusion of evidence suggesting lack of carcinogenicity? is
inevitably limited to the cancer sites, conditions and levels of exposure and length of
observation covered by the available studies. In addition, the possibility of a very
small risk at the levels of exposure studied can never be excluded.
Human No Adequate Data? or Animal No Adequate Data? have been added to the status when
the Working Group found no data available for review.
IARC also began publishing in Supplement 7, an overall evaluation? taking into consideration the
total body of evidence. In Supplement 7, and in monographs 43 onward, chemicals have been
classified in the following groups:
Group 1 The Working Group concluded that the listed agents are carcinogenic
to humans.
Group 2 The Working Group concluded that the listed agents are probably
carcinogenic to humans.
Group 2B The Working Group concluded that the listed agents are possibly
carcinogenic to humans.
Group 3 The Working Group concluded that the listed agents are not
classifiable as to their carcinogenicity to humans.
Group 4 The Working Group concluded that the listed agent is probably not
carcinogenic to humans.
For any chemical listed in RTECS速 which appears in one of these groups, its group designation is
noted in the Review field, immediately following the IARC Monograph lines.
These cancer reviews reflect only the conclusions of the IARC committees based on the data
available for the committees evaluation. Hence, for some substances there may be disagreement
between the IARC determination and the information on the tumorigenic data lines (see Section
13). Also, some substances previously reviewed by IARC may be reexamined as additional data
become available. These substances will contain multiple IARC review lines, each of which is
referenced to the appropriate IARC volume.
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Comprehensive Guide to RTECS
c.) Toxicology Reviews. The entry TOXICOLOGY REVIEWS? indicates that the cited
review article has been located in the literature. Each review is identified by its CODEN citation.
These articles discuss one or more facets of the toxicology of the substance or the general class to
which the substance belongs. Most of these references do not contain specific dose values that can
be cited in the Registry. However, the reviews do provide useful information about the toxicity of
the substance or group of related substances. The reader is cautioned that the scope of discussion
varies greatly among the reviews. Some articles may contain a complete, detailed description of
the toxicity of a substance; others may address only a particular aspect of the toxicity (e.g., effect
of a substance on fetal development, or body fluid and tissue levels of a substance found under
conditions of poisoning); and others may only list the substance in a general discussion of the
toxicity of a class of compounds.
18. Standards and Regulations (Data Type W). This section contains notations indicating the
substance is regulated by an agency of the United States Government, either by EPA, MSHA, or
OSHA, or as Occupational Exposure Limits (OEL) by other nations around the world. EPA refers
to substances regulated by the Federal Insecticide Fungicide, and Rodenticide Act (FIFRA) of the
U.S. Environmental Protection Agency. MSHA refers to standards promulgated by the Mine
Safety and Health Administration, under Subpart D, Section 56 of the Federal Mine Safety and
Health Act of 1977. These have been codified in Code of Federal Regulations (CFR) Title 30.
OSHA refers to standards promulgated under Section 6 of the Occupational Safety and Health Act
of 1970. These have been codified in 29 CFR, and are referred to as Permissible Exposure Limits
(PELs). OEL refers to the Occupational Exposure Limits published by several nations around the
world.
All United States standards and regulations are listed in the appropriate Federal Register (FR) or
Code of Federal Regulations (CFR). Because of frequent changes to and litigation of federal
regulations, it is recommended that the reader contact the applicable agency for information about
the current standards for a particular substance. Omission of a substance or regulatory notation
from the Registry does not imply any relief from regulatory responsibility.
a.) EPA FIFRA standards indicate pesticides that are subject to registration or re-registration
under the Federal Insecticide, Fungicide, and Rodenticide Act, as amended. The amendments were
issued in four parts, representing four lists of pesticides: (a) Federal Register 54(35), page7740,
Feb 22, 1989; (b) Federal Register 54(100), page 22706, March 25, 1989; (c) Federal Register
54(140), page 30848, July 24, 1989; and (d) Federal Register 54(204), page 4388, October 24,
1989.
b.) MSHA air contaminants standards are noted with the entry air,? preceded by MSHA
STANDARD.? See 30 CFR Parts 56 and 57 for additional information.
c.) OSHA air contaminant standards are noted by the entry OSHA PEL? (Permissible
Exposure Limit). The four cited sections are:
General Industry Standards 29 CFR 1910.1000
Constructions Standards 29 CFR 1926.55
Shipyard Standards 29 CFR 1915.1000
Standards for Federal Contractors 41 CFR 50-204.50.
The PEL can be further described by one or more of the following terms: ?8-hour TWA?(time-
weighted average); STEL? (short term exposure limit); or CL? (ceiling). The TWA is the
employees airborne exposure in any 8-hour work shift of a 40-hour work week which shall not be
exceeded. The STEL is the employees 15-minute time-weighted average, which shall not be
exceeded at any time during the work day. A time period other than 15 minutes may be specified
in parentheses behind the notation STEL.? The CL is the employees exposure, which shall not
be exceeded at any time during the work shift. The notation ?(skin),? following the PEL for a
substance indicates that even though the air contaminant concentration may be below the PEL,
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December 2007
significant additional exposure to the skin may be dangerous. The use of personal protective
equipment, engineering controls, or work practices is required. (Another designation is applied to
substances listed on the Z-2 table: PK,? which refers to the acceptable maximum peak
concentration above the ceiling concentration.)
Some workplace exposures consist of more than one contaminant. OSHA regulations provide for
the reduction of PELs based on additive or synergistic health effects.
OSHA Cancer Hazard and OSHA Suspect Cancer Agent designations may appear on a subsequent
data line for selected substances regulated by OSHA as carcinogens.
The reader is cautioned that some OSHA PELs are promulgated for classes of compounds rather
than for individual substances. These classes may be based on certain chemical or physical
properties that have not been well defined for every member of the class. Any questions about
specific OSHA PELs should be directed to:
OSHA
Office of Public Affairs
Room N-3647
Department of Labor
200 Constitution Avenue, NW
Washington, D.C. 20210
Telephone (202) 219-8151.
d.) International Occupational Exposure Limits (OELs). The nations whose standards are
listed, and the source from which RTECS速 obtained the OELs, are as follows:
Arab Republic of Egypt Letter from: National Institute of Occupational
Safety and Health, Heliopolis, A.R.E.
Mrs. Laila El Hariry,
General Director of the International
Relations Department
Argentina Letter from Dr. Carlos Anibal Rodrigues,
Ministerio de Trabajo y Seguridad Social de la Nacion
Buenos Aires, Argentina
Australia Occupational Safety and Health Series, No. 37
Occupational Exposure Limits for Airborne Toxic Substances
International Labour Office, Geneva
Austria Maximale Arbeitsplatz-Konzentrationen
Gesundheitssch辰dlicher Arbeitsstoffe
MAK-Werte-Liste
Belgium Occupational Safety and Health Series, No. 37
Occupational Exposure Limits for Airborne Toxic Substances
International Labour Office, Geneva
Colombia Letter from: Consejo Colombiano de Seguridad
Renan Alfonso Rojas Gutierrez,
Executive Director
Denmark Gr脱nsev脱rdier for stoffer og materialer
Copenhagen
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Comprehensive Guide to RTECS
France Valeurs limites dexposition professionnelle
Aux agents chimiques en France
Germany Deutsche Forschungsgemeinschaft
List of MAK and BAT Values, 1974
Commission for the Investigation of
Health Hazards of Chemical Compounds
In the Work Area
Report No. 30
Hungary Letter from: ORSZAGOS
Munkavedelmi Tudomanyos Kutat坦 Int辿zet
Dr. Jen坦 Molnar, Director
India Directorate General Factory Advice Service
and Labour Institute
Government of Industry, Ministry of Labour
H. N. Gupta, Director General
Japan Occupational Exposure Limits for Airborne
Toxic Substances
Occupational Safety and Health Series, No.37
International Labour Office, Geneva
Jordan Letter from: The Hashemite Kingdom of Jordan
Vocational Training Corporation
Occupational Safety and Health Institute
A. Abdel-Jaber,
Director
Korea Korea Industrial Safety Corporation (KISCO)
Industrial Safety and Health Research Institute
Seoul, Korea
Park Pil - Soo, December 21, 1996
The Netherlands De Nationale MAC-lijst - 1995 - P 145
New Zealand Letter and booklet (Workplace Exposure
Standards) from: Occupational Safety and Health
General Managers Office
Wellington, New Zealand
Phillip Marshal, Information Manager
Norway Letter and list from:
Direktortet for Arbeidstilysnet
Oslo, Norway
Nils-Petter Wedege,
Deputy Director-General
The Philippines Letter from: Republic of the Philippines;
Occupational Safety and Health Center;
Department of Labor and Employment
Evelyn F. Tablang, Officer-in-Charge
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December 2007
Poland Interdepartmental Commission for Updating the
Register of Maximum Allowable Concentrations and
Intensities for Harmful Agents in the Working
Environment
Ministry of Labour and Social Policy
Poland
Portugal Letter from Instituto de Desenvolvimento e
Inspec巽達o das Condi巽探es de Trabalho
lvaro Dur達o
O Vice-presidente
Lisboa, Portugal
Russia Occupational Exposure Limits for Airborne
Toxic Substances
International Labour Office, Geneve
Singapore Letter from: Republic of Singapore
Department of Industrial Health
Ministry of Labour
Tan Kia Tang, Director
Sweden Statute Book of the Swedish National Board
Of Occupational Safety and Health:
Occupational Exposure Limit Values
Switzerland Valeurs limites dexposition and postes de travail
SUVA-CNA-INSAI
Thailand Letter and table of values from:
National Institute for the Improvement of
Working Conditions and Environment (NICE)
Department of Labour
Bangkok, Thailand
Dr. Chaiyuth Chavalitnitikul, Director
Turkey Letter from: Occupational Health and
Safety Institute P.K. 393
06443 YeniSehir
Ankara, Turkey
Dr. Handan Uysal Sabir, Director
United Kingdom Occupational Exposure Limits
Guidance Note EH 40/95
Health and Safety Executive
19. NIOSH Standards Development and Surveillance Data (Data Type X). This section contains
information generated by NIOSH in two areas of endeavor. The Standards Development Programs
produces Recommended Exposure Levels (RELs). The Surveillance Program has conducted two
nationwide surveys of work sites and some of its findings are noted in this field.
a.) NIOSH Recommended Exposure Level (REL). This section indicates that a NIOSH
recommendation for occupational exposure has been published. The RELs may appear in any of
several document forms: Criteria Documents, Current Intelligence Bulletins, Special Hazard
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Comprehensive Guide to RTECS
Reviews, Occupational Hazard Assessments, and Technical Guidelines. NIOSH also periodically
presents testimony before various Congressional committees and at regulatory hearings convened
by OSHA and MSHA. The testimony presented always includes the current NIOSH policy
concerning the particular hazard in question. A compendium of NIOSH recommendations is
contained in DHHS (NIOSH) Publication 92-100 and further revisions can be found in DHHS
(NIOSH Publication 95-121).
b.) NIOSH Occupational Exposure Survey data. NIOSH Survey Data (NOHS, 1974, or NOES,
1983) lines indicate that data on potential occupational exposure to the substance exist in one or
both of the databases assembled as a result of national surveys of industry in the United States.
The first survey, the National Occupational Hazard Survey (NOHS) was conducted from February
1972 to June 1974; the second, the National Occupational Exposure Survey (NOES) from
November 1980 to May 1983. The intent of both surveys was to associate potential exposure
agents (chemical, physical, and biological) with industry types, occupations, and specific surveyed
facilities.
In both surveys, the sample of surveyed facilities was designed to permit projections to the
national level based, on survey results. It is possible, for example, to estimate the total number of
people potentially exposed to a particular agent. Among other data reporting capabilities of each
survey are the actual number of industries, occupations, or facilities in which an agent was
observed.
There are several limitations, dictating the need for caution, and some reservations that must be
observed in the interpretation and any subsequent use of the occupational exposure data presented
in this field.
? The occupational exposure data presented for each survey were representative of the
workplace at the respective times each survey was conducted. The data are becoming
progressively more dated, and as a consequence, less representative of the current
situation.
? Data in both surveys were collected using observational techniques. No environmental
levels of chemical or biological contaminants or degrees of physical hazards were
actually measured.
? Neither survey covered industries in mining or agriculture. The sample universe of the
NOHS did not include rural areas. The NOES did not include Federal, State, or local
governments, financial, real estate, or retail trade industries.
? Exposure data reported for both surveys are provisional. In both cases, the majority of
exposure data (approximately 70%) recorded during both surveys was by trade name
product. Subsequent detailed component information for these trade name products was
sought from the manufacturers and incorporated into the respective survey databases.
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December 2007
Basic Parameters of both surveys are as follows:
Survey
Parameter NOHS NOES
Start date of field survey February 1972 November 1980
End date for field survey June 1974 May 1983
Estimated number of plants in the survey universe 739,244 508,697
Estimated number of employees in the survey universe 38,262,627 33,409,031
Number of plants surveyed 4,636 4,490
Number of employees surveyed 893,725 1,830,330
Number of different occupations surveyed 453 410
Number of agents seen 8,000+ 9,000+
Number of unique trade name products 80,000 100,000
Types of data appearing on the survey data lines for each substance and the abbreviations used in
the text are as follows.
HAZARD CODE (HZD) - a five-position identifier used exclusively for search and retrieval of
data from either survey database.
NUMBER OF INDUSTRIES (NIS) - number of industries, as defined by standard 4-digit
industrial classification (SIC) codes, in which the agent was observed.
TOTAL NUMBER OF FACILITIES (TNF) - estimated (nationwide) total number of facilities in
which the agent is thought to be present.
NUMBER OF OCCUPATIONS (NOS) - number of occupations, as defined by the Bureau of
Census Occupational codes, in which the agent was observed.
TOTAL NUMBER OF EMPLOYEES (TNE) - estimated (nationwide) total number of employees
thought to be exposed to the agent.
TOTAL NUMBER OF FEMALE EMPLOYEES (TFE)* - estimated (nationwide) total number of
female employees thought to be exposed to the agent.
*NOTE: These data are available for the NOES only.
Questions specific to the occupational survey data reported in the Registry should be directed to:
NIOSH
DSHEFS
Mail Stop R-12
4676 Columbia Parkway
Cincinnati, Ohio 45226
Detailed descriptions of the surveys and their resulting databases are available in the following
NIOSH technical reports:
Survey Manual (NOHS)
DHEW (NIOSH) Publication No. 74-127 (1974)
Data Editing and Database Development (NOHS)
DHEW (NIOSH) Publication No. 77-213 (1977)
Survey Analysis and Supplemental Tables (NOHS)
DHEW (NIOSH) Publication No. 78-114 (1977)
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Comprehensive Guide to RTECS
Survey Manual (NOES)
DHHS (NIOSH) Publication No. 88-106 (1987)
Sampling Methodology (NOES)
DHHS (NIOSH) Publication No. 89-102 (1989)
Analysis of Management Interview Responses (NOES)
DHHS (NIOSH) Publication No. 89-103 (1989)
20. ATSDR, EPA, NIOSH, NTP and OSHA Status (Data Type Y). This section provides information
on the activities of various governmental agencies regarding the substance. Status lines are
currently listed for ATSDR, EPA, NIOSH, NTP, and OSHA.
a.) The Agency for Toxic Substances and Disease Registry (ATSDR) has been directed by the
Superfund Amendments and Reauthorization Act of 1986 (SARA) to prepare toxicological
profiles for hazardous substances that pose the most significant potential threat to human health, as
determined by ATSDR and the Environmental Protection Agency (EPA). Each profile is intended
to characterize the toxicological and adverse health effects information for the hazardous
substance being described. The currently available profiles are noted in the Status field of the
appropriate chemical records. Also noted is the National Technical Information Service (NTIS)
Stock Number of each profile.
b.) The Environmental Protection Agency (EPA) status entries are included for five portions of
the Toxic Substances Control Act (TCSA), Public Law 94-469: Section 8(a) preliminary
assessment information, Section 8(b) chemical inventory, Section 8(d) health and safety studies,
Section 8(e) substantial risk information, and TSCA Test Submissions Database (TSCATS).
Additional status lines are listed for two other EPA programs: A genetic toxicology online data
base (GENE-TOX) and the Integrated Risk Information System (IRIS).
A TSCA inventory citation indicates that the substance appears on the Chemical Inventory
prepared in 1986 by the EPA in accordance with provisions of Section 8(b) of TSCA. Substances
reported in the inventory include those that are produced commercially in or imported into this
country. The reader should note, however, that substances already regulated by EPA under FIFRA
and by the Food and Drug Administration (FDA) under the Food, Drug, and Cosmetic Act, as
amended, are not included in the TSCA inventory. Similarly, alcohol, tobacco, and explosive
substances are not regulated under TSCA. TSCA regulations should be consulted for an exact
definition of reporting requirements.
A preliminary assessment information status line indicates that EPA has promulgated both a final
and a proposed rule under Section 8(a) of TSCA, reporting and retention of information. The final
rule requires chemical manufacturers and, in some cases, processors and importers to report
production and exposure-related data to EPA. Included in this status line is a citation to the
Federal Register issue (volume 47, page 26992, June 22, 1982) in which the rule appeared. This
reference should be consulted for a complete explanation of the rule. The proposed rule (Federal
Register, volume 47, page 27009, June 22, 1982) covers an additional 350 chemicals for which
similar reporting would be required.
Under TSCA Section 8(d), manufacturers, importers, and/or processors of a substance specified by
the EPA Administrator must submit lists and copies of unpublished health and safety studies on
that substance. Specified substances include chemical substances that are selected for
consideration for testing rules under TSCA section 4, as well as other chemicals that EPA had
identified as of concern under TSCA. A health and safety? study is interpreted broadly and may
include not only formal studies but also other types of information relating to health and
environmental effects, including relevant monitoring and exposure data.
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December 2007
A substantial risk status line indicates that EPA has received and reviewed information submitted
under Section 8(e) of TSCA, which requires that persons who obtain information which
reasonably supports the conclusion that a substance presents substantial risk of injury to human
health or the environment must notify EPA within 15 days. These notices are reviewed by EPA
and an initial evaluation is prepared containing, if appropriate, follow-up questions to the
submitter, referrals to other agencies, and decisions to list the chemical for a Section 8 reporting
rule or to undertake a formal risk assessment. The reader should note that many 8(e) notices
represent a companys first review of a situation or datum and a judgment in compliance with the
statute to submit a notice within 15 days of obtaining the information. EPA published its
evaluations of these notices in order to make widely available this Section 8(e) information in a
form understandable to the general public.
The TSCATS was developed to make unpublished test data submitted to EPA available to the
public. Test is broadly defined to include case reports, episodic incidents (such as spills), and
formal test study presentations. The database allows searching of test submissions according to
specific chemical identity or type of study. Studies are indexed under three broad subject areas:
health effects, environmental effects, and environmental fate. Additional controlled vocabulary
index terms are assigned that describe the experimental protocol and test observations. Records
identify reference information needed to locate the source document, as well as the submitting
organization and reason for submission of the test data.
GENE-TOX: A Genetic Toxicology program status line indicates that the substance has been
reported in the literature for potential genetic effects. The test protocol in the literature is evaluated
by an EPA Expert Panel on Mutations and a positive or negative effect of the substance is
evaluated and reported. To obtain additional information about this program, contact GENE-TOX
Program, EPA, 401 M Street SW, TS796, Washington, D.C. 20460, telephone (202) 260-1513.
IRIS: The Integrated Risk Information System is the EPA electronic on-line database of summary
health risk assessment and regulatory information on chemical substances. The primary purpose of
IRIS is to provide guidance risk values to EPA risk assessors and decision makers for use in EPA
risk management decisions. EPA staff and EPA contractors are expected to use the risk
information in IRIS for those chemicals in the database. The information contained in IRIS, except
as specifically noted, has been reviewed and agreed upon by intra-agency review groups
comprised of EPA scientists, having extensive experience in risk assessment. Thus, the
information in IRIS represents an expert Agency consensus.
c.) NIOSH status lines are included for those substances for which an analytical method(s) has
been developed by NIOSH or for substances for which NIOSH Current Intelligence Bulletins
(CIBs) have been issued. The chemicals listed in the Fourth Edition of the NIOSH Manual of
Analytical Methods (NMAM)? are also cited in the RTECS速. The sampling and measurement
methods in the NMAM Fourth Edition are revisions and additions to those contained in the
previous editions
d.) National Toxicology Program (NTP). There are two types of status lines listed in the
RTECS速 file. The first indicates that the substance has been or is being tested by the NTP under its
Carcinogenesis Testing Program. These entries were identified as National Cancer Institute (NCI)
status lines in issues of the Registry prior to July 1980. However, the NCI Carcinogenesis Testing
Program has been absorbed by NTP, and subsequent status lines have been reformatted
accordingly. The following different citations are used to reflect the current test status of the
compound: nominated for test; selected for test; currently undergoing test; or test completed.
These citations are updated as each bioassay progresses. Selection of a chemical for bioassay does
not necessarily imply that it is a carcinogen. Also, a compound originally selected and even
scheduled for bioassay may be withdrawn from the program anytime during testing or before
testing actually begins. This initial selection is cited in the Registry but is deleted when the
compound is removed from the test. The bioassay itself normally takes about two and one half
years to conduct, and another year is required to prepare the final report. When this report is
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Comprehensive Guide to RTECS
released, the report number and test results are listed, and, where applicable, specific tumorigenic
dose lines (see Section 13) are generated.
In June 1983, then revised in 1986, NTP adopted five categories of interpretive conclusions for
use in their technical reports. The Registry citations make use of these same five categories in the
NTP Status Lines. As defined by NTP, the categories (which refer to the strength of the
experimental evidence) are as follows:
CLEAR EVIDENCE of Carcinogenicity Activity is demonstrated by studies that are interpreted as
showing a dose-related (i) increase of malignant neoplasms, (ii) increase of a combination of
malignant and benign neoplasms, or (iii) marked increase of benign neoplasms if there is an
indication from this or other studies of the ability of such tumors to progress to malignancy.
SOME EVIDENCE of Carcinogenicity Activity is demonstrated by studies that are interpreted as
showing a chemical-related increased incidence of neoplasms (malignant, benign, or combined), in
which the strength of the response is less than that required for clear evidence.
EQUIVOCAL EVIDENCE of Carcinogenicity Activity is demonstrated by studies that are
interpreted as showing a marginal increase of neoplasms that may be chemically related.
NO EVIDENCE of Carcinogenicity Activity is demonstrated by studies that are interpreted as
showing no chemical-related increases in malignant or benign neoplasms.
INADEQUATE STUDY of Carcinogenicity Activity is demonstrated by studies that because of
major qualitative or quantitative limitations cannot be interpreted as valid for showing either the
presence or absence of carcinogenic activity.
Final reports for some bioassays may not be published because the data are insufficient, and this is
noted in the Registry where applicable. Also, some substances may be selected by NTP for retest
after the first bioassay is completed and the final report issued. These duplicate studies are noted
on a separate NTP status line. Some of the early NCI testing was not done in accordance with the
strict experimental protocols now used. The results of these studies were not published as NCI
bioassay reports, but instead appeared in the literature as journal articles. These are noted on the
NTP status lines as studies? rather than bioassays,? and reference to the journals are given. To
obtain additional information about the Carcinogenesis Testing Program or the status of a
particular substance under test, or to obtain copies of the final bioassay reports, contact the Central
Data Management, Mail Drop E1-02, NIEHS, P.O. Box 12233, Research Triangle Park, North
Carolina 27709, telephone (919) 541-3991.
The second type of NTP status line indicates that the substance is listed in the NTP, Report on
Carcinogens (RoC). This cumulative list is published in accordance with Public Law 95-622,
which requires that the Secretary of Health and Human Services publish a biennial report
containing ?. . . a list of all substances (1) which either are known to be human carcinogens or
which may reasonable be anticipated to be human carcinogens and (2) to which a significant
number of persons residing in the United States are exposed . . .? Included for each of the
chemicals in the report is a description of the substance, including a brief synopsis of the scientific
evidence that led to its inclusion in the report. This is immediately followed by information about
the regulatory activities of the NTP-participating federal agencies.
The criteria for listing a substance are as follows:
Known To Be Human Carcinogen:
There is sufficient evidence of carcinogenicity from studies in humans, which indicates a causal
relationship between exposure to the agent, substance, or mixture, and human cancer.
Reasonably Anticipated To Be Human Carcinogen:
- 34 -
December 2007
There is limited evidence of carcinogenicity from studies in humans, which indicates that causal
interpretation is credible, but that alternative explanations, such as chance, bias, or confounding
factors, could not adequately be excluded,
or
there is sufficient evidence of carcinogenicity from studies in experimental animals, which
indicates there is an increased incidence of malignant and/or a combination of malignant and
benign tumors (1) in multiple species or at multiple tissue sites, or (2) by multiple routes of
exposure, or (3) to an unusual degree with regard to incidence, site, or type of tumor, or age at
onset,
or
there is less than sufficient evidence of carcinogenicity in humans or laboratory animals; however,
the agent, substance, or mixture belongs to a well-defined, structurally related class of substances
whose members are listed in a previous Report on Carcinogens as either known to be a human
carcinogen or reasonably anticipated to be a human carcinogen, or there is convincing relevant
information that the agent acts through mechanisms indicating it would likely cause cancer in
humans.
For additional information about the report, contact the National Toxicology Program, P.O. Box
12233, Research Triangle Park, North Carolina 27709, telephone (919) 541-4096.
e.) OSHA Status: The OSHA status line reports that a validated analytical method(s) has been
developed for the chemical by OSHA and appears in its Manual of Analytical Methods. The
methods can be found on-line at www.osha.gov/dts/sltc/methods.
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Comprehensive Guide to RTECS
Table I. RTECS速 Abbreviations
asn Aspergillis nidulans hmn human
ast Ascites tumor hor horse, donkey
bcs Bacillus subtilis I intermittent
bfa body fluid assay ial intra-aural
BHR Beilstein Handbook Reference IARC International Agency for
Research on Cancer
bmr bone marrow iat intra-arterial
brd bird (domestic) ice intracerebral
BRN Beilstein Reference Number icv intracervical
bwd wild bird species idr intradermal
C continuous idu intraduodenal
cc cubic centimeter ihl inhalation
chd child imm immersion
ckn chicken imp implant
CL ceiling concentration ims intramuscular
clr Chyamydomonas reinhardi inf infant
ctl cattle ipc intraplacental
cyt Cytogenetic Analysis ipl intrapleural
D day ipr intraperitoneal
dck duck irn intrarenal
DEF definition isp intraspinal
dlt Dominant Lethal Strain itr intratracheal
dmg Drosophila melanogaster itt intratesticular
dna DNA Adduct iu international unit
dnd DNA Damage iut intra-uterine
dni DNA Inhibition ivg intravaginal
dnr DNA Repair ivn intravenous
dns Unscheduled DNA Synthesis kdy kidney
dom domestic kg kilogram (one thousand grams)
DOT Department of Transportation klp Klebsiella pneumoniae
dpo Drosophila pseudo-obscura L liter
emb embryo LC50 lethal concentration, 50 percent
kill
EPA Environmental Protection LCLo lowest published lethal
Agency concentration
esc Escherichia coli LD50 lethal dose, 50 percent kill
eug Euglena gracilis LDLo lowest published lethal dose
eye administration into the eye leu leukocyte
(irritant)
fb fiber liq liquid
fbr fibroblast lng lung
frg frog lvr liver
gm gram lym lymphocyte
gpg guinea pig M minute
m3
grb gerbil cubic meter
grh grasshopper mam mammal (species unspecified)
H hour mg milligram (one thousandth of a
gram, 10 -3 gram)
ham hamster mky monkey
hla HeLa cell mL milliliter
hma Host-mediated Assay MLD mild irritant effect
hmi Haemophilus influenzae
- 36 -
December 2007
速
Table I. RTECS Abbreviations (continued)
mmo Mutation in Micro-organism pre prior to copulation
mmol millimole preg pregnant
mmr mammary gland qal quail
mnt Micronucleus test rat rat
MOD moderate irritation effect rbt rabbit
mol mole rec rectal
mppcf million particles per cubic foot REGS Standards and Regulations
mrc Gene Conversion and Mitotic REL Recommended Exposure Level
Recombination
msc Mutation in Mammalian Somatic rns rinsed with water
Cells
MSHA Mine Safety and Health RTECS Registry of Toxic Effects of
Administration Chemical Substances
mtr Morphological Transform S second
mul multiple routes sal salmon
mus mouse sat Salmonella typhimurium
ng nanogram (one billionth of a sce Sister Chromatid Exchange
gram, 10 -9 gram)
nml non-mammalian species SCP Standards Completion Program
nmol nanomole scu subcutaneous
NOES National Occupational Exposure SEV severe irritation effect
Survey
NOHS National Occupational Hazard skn administration onto the skin
Survey
nsc Neurospora crassa sln Sex Chromosome Loss and
Nondisjunction
NTP National Toxicology Program slw silkworm
OBS obsolete (trade name) smc Saccharomyces cerevisiae
ocu ocular spm Sperm Morphology
OEL Occupational Exposure Limit sql squirrel
ofs other fish srm Serratia marcescens
omi other micro-organisms ssp Schizosaccharomyces pombe
oms other mutation test systems STEL Short-Term Exposure Limit
oin other insects TC toxic concentration (other than
lowest)
open open irritation test TDLo lowest published toxic dose
orl oral tes testis
ORM Other Regulated Materials TLV Threshold Limit Value
(DOT)
OSHA Occupational Safety and Health tod toad
Administration
oth other cell types trk turkey
ovr ovary trn Heritable Translocation Test
par parenteral TWA time-weighted average
PEL Permissible Exposure Limit unr unreported
(OSHA)
pg picogram (one trillionth of a W week
gram, 10 -12 gram)
pgn pigeon wmn woman
pic Phage Inhibition Capacity Y year
亮g
pig pig microgram (one millionth of a
gram, 10 -6 gram)
亮mole
pph parts per hundred (v/v) (percent) micromole
ppm parts per million (v/v)
ppt parts per trillion (v/v)
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Comprehensive Guide to RTECS
Table II. Toxic Effects Codes (TEC)
Position 1 - Organ, Tissue, or Functional System
A Brain and Coverings
B Spinal Cord
C Peripheral Nerves and Sensation
D Sense Organs and Special Senses (Nose, Eye, Ear, and Taste)
E Autonomic Nervous System
F Behavioral
G Cardiac
H Vascular
J Lung, Thorax, or Respiration
K Gastrointestinal
L Liver
M Kidney, Ureter, and Bladder
N Endocrine
P Blood
Q Musculoskeletal
R Skin and Appendages
T Reproductive
U Nutritional and Gross Metabolic
V Tumorigenic
Y Biochemical
Z Related to Chronic Data
- 38 -
December 2007
Table II. Toxic Effects Code (TEC) (Continued)
Positions 2 and 3 - Damage Codes, two digits
Each of the major headings below corresponds to one of the organs, tissues, or functional systems listed in
Position 1.
A. Brain and Coverings
01 Meningeal changes
02 Changes in cerebral spinal fluid
03 Increased intracranial pressure
04 Changes in circulation (Hemorrhage, thrombosis, etc.)
05 Encephalitis
06 Demyelination
10 Changes in surface EEG
11 Recordings from specific areas of CNS
30 Other degenerative changes
60 Tumors
70 Changes in brain weight
B. Spinal Cord
01 Meningeal changes
02 Changes in circulation
03 Inflammatory changes
04 Demyelination
30 Other degenerative changes
60 Tumors
C. Peripheral Nerve and Sensation
01 Associated connective tissue
02 Sensory syndrome diagnostic of central lesion
03 Sensory change involving trigeminal nerve
04 Sensory change involving peripheral nerve
05 Sensory change involving segmental distribution
06 Spastic paralysis with or without sensory change
07 Flaccid paralysis with appropriate anesthesia
08 Flaccid paralysis without anesthesia (usually neuromuscular blockage)
09 Fasciculations
10 Paresthesis
15 Recording from afferent nerve
16 Recording from peripheral motor nerve
17 Local anesthetic
18 Structural change in nerve or sheath
60 Peripheral nerve tumors
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Comprehensive Guide to RTECS
Table II. Toxic Effects Code (TEC) (Continued)
D. Sense Organs and Special Senses (Nose, Eye, Ear, and Taste)
Olfaction:
01 Deviated nasal septum
02 Ulcerated nasal septum
03 Change in olfactory nerve
04 Change in sensation of smell
07 Other changes
09 Tumors
Eye:
10 Optic nerve neuropathy
11 Cycloplegia
12 Changes in refraction
13 Ciliary spasm
14 Visual field changes
15 Miosis (pupillary constriction)
16 Mydriasis (pupillary dilation)
17 Lacrimation
18 Chromodacryorrhea
19 Increased intraocular pressure
20 Retinal changes (pigmentary depositions, retinitis, other)
21 Hemorrhage
22 Changes in circulation
23 Diplopia
24 Changes in extra-ocular muscles
25 Conjunctive irritation
26 Corneal damage
27 Iritis
28 Ptosis
29 Tumors
35 Other
Ear:
40 Change in acuity
41 Tinnitus
43 Changes in vestibular functions
44 Changes in cochlear structure or function
45 Other
Taste:
50 Change in taste function
- 40 -
December 2007
Table II. Toxic Effects Code (TEC) (Continued)
E. Autonomic Nervous System
01 Sympathomimetric
02 Alpha adrenergic blockage
03 Beta adrenergic blockage
04 Central sympatholytic
05 Ganglion blocker
06 Ganglion facilitant
08 Other (direct) parasympathomimetic
09 Intensity beta adrenergic effects
15 Smooth muscle relaxant (mechanism undefined, spasmolytic)
16 Parasympatholytic
F. Behavioral
01 General anesthetic
02 Anticonvulsant
03 Wakefulness
04 Sleep
05 Altered sleep time (including change in righting reflex)
06 Euphoria
07 Somnolence (general depressed activity)
08 Hallucinations, distorted perceptions
09 Change in REM sleep (human)
10 Toxic psychosis
11 Tremor
12 Convulsions or effect on seizure threshold
13 Excitement
14 Anorexia (human)
15 Food intake (animal)
16 Fluid intake
17 Changes in motor activity (specific assay)
18 Muscle weakness
19 Ataxia
20 Stiffness
21 Rigidity (including catalepsy)
22 Tetany
23 Muscle contraction or spasticity
24 Coma
25 Antipsychotic
26 Antianxiety
27 Headache
29 Analgesia
30 Tolerance
31 Withdrawal
32 Abuse
33 Irritability
34 Straub tail
40 Alteration of classical conditioning
41 Alteration of operant conditioning
42 Changes in psychophysiological tests
43 Aggression
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Comprehensive Guide to RTECS
Table II. Toxic Effects Code (TEC) (Continued)
G. Cardiac
01 Cardiomyopathy, including infarction
02 Changes in coronary arteries
03 Pericarditis
04 Arrhythmias (including changes in conduction)
05 Cardiomegaly
06 EKG changes not diagnostic of above
07 Pulse rate increase without fall in BP
08 Pulse rate
09 Change in force of contraction
10 Change in rate
11 Change in conduction velocity
12 Cardiac output
13 Changes in resting or action potential
30 Other changes
60 Tumors
70 Changes in heart weight
H. Vascular
01 BP elevation not characterized in autonomic section
02 BP lowering not characterized in autonomic section
03 Pulse pressure increase
04 Regional or general arteriolar constriction
05 Regional or general arteriolar or venous dilation
06 Measurement of regional blood flow
07 Change in plasma or blood volume
08 Shock
15 Acute arterial occlusion
16 Structural changes in vessels
17 Thrombosis distant from injection site
20 Contraction (isolated tissues)
21 Relaxation (isolated tissues)
30 Other changes
35 Effect on gills and gill functions
60 Tumors
J. Lungs, Thorax, or Respiration
01 Ciliary function changes
02 Structural or functional change in trachea or bronchi
03 Bronchiolar dilation
04 Bronchiolar constriction
05 Bronchiectasis
06 Emphysema
07 Changes in pulmonary vascular resistance
08 Consolidation
12 Fibrosis, focal (pneumoconiosis)
13 Fibrosis (interstitial)
14 Fibrosing alveolitis
15 Acute pulmonary edema
16 Chronic pulmonary edema
17 Pleural effusion
18 Pleural thickening
20 Respiratory obstruction
- 42 -
December 2007
Table II. Toxic Effects Code (TEC) (Continued)
21 Cough
22 Dyspnea
23 Sputum
24 Cyanosis
25 Respiratory depression
26 Respiratory stimulation
27 Pulmonary emboli
30 Other changes
60 Tumors
61 Bronchiogenic carcinoma
70 Changes in lung weight
K. Gastrointestinal
01 Changes in structure or function of salivary glands
02 Changes in structure or function of endocrine pancreas
03 Changes in structure or function of esophagus
04 Alteration in gastric secretion
05 Gastritis
06 Ulceration or bleeding from stomach
07 Ulceration or bleeding from duodenum
08 Ulceration or bleeding from small intestine
09 Ulceration or bleeding from large intestine
12 Hypermotility, diarrhea
13 Nausea or vomiting
14 Decreased motility or constipation
15 Malabsorption
17 Peritonitis
20 Necrotic changes
30 Other changes
31 Contraction (isolated tissue)
32 Relaxation (isolated tissue)
60 Tumors
61 Colon tumors
70 Changes in pancreatic weight
L. Liver
01 Hepatitis (hepatocellular necrosis), diffuse
02 Hepatitis (hepatocellular necrosis), zonal
03 Fatty liver degeneration
04 Hepatitis, fibrous (cirrhosis, post-necrotic scarring)
11 Jaundice, cholestatic
12 Jaundice, other or unclassified
14 Liver function tests impaired
15 Changes in gall bladder structure or function
19 Jaundice (or hyerbilirubinemia) hepatocellular
30 Other changes
50 Multiple effects
60 Tumors
61 Angiosarcoma
70 Changes in liver weight
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Comprehensive Guide to RTECS
Table II. Toxic Effects Code (TEC) (Continued)
M. Kidney, Ureter, and Bladder
01 Changes in blood vessels or in circulation of kidney
02 Changes primarily in glomeruli
03 Changes in tubules (including acute renal failure, acute tubular necrosis)
04 Changes in both tubules and glomeruli
05 Interstitial nephritis
10 Urine volume increased
11 Urine volume decreased
12 Renal function tests depressed
13 Proteinuria
14 Hematuria
16 Other changes in urine composition
20 Inflammation, necrosis, or scarring of bladder
21 Structural or functional changes in ureter
29 Incontinence
30 Other changes
60 Tumors
61 Kidney tumors
70 Changes in bladder weight
71 Changes in kidney weight
N. Endocrine
01 Antidiuresis
02 Changes in LH
03 Changes in GH
04 Change in gonadotropins
05 Thyroid weight (goiter)
06 Toxic goiter - hypofunction
07 Evidence of thyroid hyperfunction
08 Evidence of thyroid hypofunction
10 Hyperparathyroidism
12 Adrenal cortex hyperplasia
13 Adrenal cortex hypoplasia
15 Aldosternism
16 Androgenic
17 Estrogenic
18 Differential effect of sex or castration on observed toxicity
19 Effect on menstrual cycle
20 Gynecomastia
21 Diabetes mellitus
22 Hypoglycemia
23 Ketosis
24 Hyperglycemia
25 Diabetes insipidus (nephrogenic or CNS)
30 Other changes
60 Tumors
61 Adrenal cortex tumors
62 Thyroid tumors
70 Changes in endocrine weight (unspecified)
71 Changes in pituitary weight
72 Changes in adrenal weight
73 Changes in spleen weight
74 Changes in thymus weight
75 Changes in thyroid weight
- 44 -
December 2007
Table II. Toxic Effects Code (TEC) (Continued)
P. Blood
01 Hemorrhage
02 Change in clotting factors
05 Normocytic anemia
06 Microcytosis with or without anemia
07 Macrocytosis
08 Pigmented or nucleated red blood cells
13 Granulocytopenia
14 Leukopenia
15 Agranulocytosis
16 Eosinophilia
17 Thrombocytopenia
20 Changes in cell count (unspecified)
22 Oxidant-related (GPD-deficient) anemia
23 Other hemolysis with or without anemia
24 Methemoglobinemia-Carboxyhemoglobin
25 Aplastic anemia
26 Changes in bone marrow not included above
27 Changes in spleen
28 Changes in serum composition (e.g., TP, bilirubin, cholesterol)
30 Other changes
60 Tumors
61 Leukemia
62 Lymphoma, including Hodgkin's disease
70 Changes in other cell count (unspecified)
71 Changes in erythrocyte (RBC) count
72 Changes in leucocyte (WBC) count
73 Changes in platelet count
Q. Musculoskeletal
See also Behavioral for muscle change secondary to CNS or metabolic changes.
01 Changes in teeth and supporting structures
02 Osteoporosis
10 Osteomalacia
15 Joints
30 Other changes
60 Tumors
R. Skin and Appendages
Skin
After systemic exposure:
01 Dermatitis, allergic
02 Dermatitis, irritative
03 Dermatitis, other
04 Photosensitivity
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Comprehensive Guide to RTECS
Table II. Toxic Effects Code (TEC) (Continued)
After topical exposure:
10 Primary irritation
11 Corrosive
12 Dermatitis, allergic
13 Cutaneous sensitization (experimental)
14 Photosensitivity
Other:
20 Sweating
21 Hair
22 Nails
25 Breast
30 Other glands
60 Tumors
S. Immunological, including Allergic
01 Increase in cellular immune response
02 Decrease in cellular immune response
03 Increase in humoral immune response
04 Decrease in humoral immune response
05 Decreased immune response
06 Increased immune response
Allergic (Multiple organ involvement)
When single organs are involved, coded under organ.
Cholesterol jaundice - see Liver.
Aplastic anemia, agranulocytoses - see Blood.
Allergic dermatitis - see Skin.
15 Anaphylaxis
16 Other immediate (humoral) uticaria, allergic rhinitis, serum sickness
18 Hypersensitivity delayed
20 Autoimmune
25 Uncharacterized
U. Nutritional and Gross Metabolic
See also Biochemical (Intermediary Metabolism).
Gross Metabolite Changes
01 Weight loss or decreased weight gain
02 Conditioned vitamin deficiency
03 Dehydration
Changes in Chemistry or Temperature
05 Na
06 Cl
07 Ca
08 P
09 Fe
10 K
11 Other metals
20 Metabolic acidosis
21 Metabolic alkalosis
25 Body temperature increase
- 46 -
December 2007
Table II. Toxic Effects Code (TEC) (Continued)
28 Body temperature decrease
30 Other changes
V. Tumorigenic
01 Carcinogenic by RTECS criteria
02 Neoplastic by RTECS criteria
03 Equivocal tumorigenic agent by RTECS criteria
05 Cells (cultured) transformed
08 Increased incidence of tumors in susceptible strains
10 Tumors at site of application
15 Tumor types after systemic administration not seen spontaneously
16 Facilitates action of known carcinogen
25 Protects against induction of experimental tumors
30 Active as anti-cancer agent
Y. Biochemical
Enzyme inhibition, induction, or change in blood or tissue levels
01 True cholinesterase
02 Other esterases
03 Phosphatases
04 Other hydrolases
05 Carbonic anhydrase
06 Xanthine oxidases
07 Hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)
08 Monoamine oxidase
09 Cytochrome oxidases (including oxidative phosphorylation)
10 Dehydrogenases
11 Catalases
12 Other oxidoreductases
13 Phosphokinase
14 Hexokinases
15 Transaminases
16 Other transferases
17 Peptidases
18 Proteases
19 Isomerases
20 Multiple enzyme effects
21 Other enzymes
23 Reactivates cholinesterase
Effect on specific coenzyme:
25 B vitamins, including folate
26 CoA
27 NAD, NADP
28 Others
29 Proportion of isoenzymes
30 Disturbed regulation
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Comprehensive Guide to RTECS
Table II. Toxic Effects Code (TEC) (Continued)
Metabolism (intermediary):
35 Xanthine, purine, or nucleotides, including urate
36 Porphyrin, including bile pigments
37 Lipids, including transport
38 Amino acids (including renal excretion)
39 Plasma proteins not involving coagulation
40 Other proteins
41 Glycolytic
42 TCS cycle
43 Pentase shunt
44 Other carbohydrates
45 Histamines (including liberation not immunochemical in origin)
50 Effect on mitochondrial function
51 Effect on active transport
52 Effect on Na-K pump
53 Other
54 Effect on cyclic nucleotides
55 Effect on inflammation or mediation of inflammation
Neurotransmitters or modulators (putative)
60 Catecholamine levels in sympathetic nerves
61 Catecholamine levels in CNS
64 Dopamine in striatum
65 Dopamine at other sites
Z. Related to Chronic Data
01 Death in the Other Multiple Dose data type field
71 Changes in ovarian weight
72 Changes in prostate weight
73 Changes in testicular weight
74 Changes in uterine weight
- 48 -
December 2007
Table III. Reproductive Effects Code
Paternal Effects
T01 Spermatogenesis (including genetic material, sperm morphology, motility, and count)
T02 Testes, epididymis, sperm duct
T03 Prostate, seminal vesicle, Cowper's gland, accessory glands
T04 Impotence
T05 Breast development
T09 Other effects in male
Maternal Effects
T11 Oogenesis
T12 Ovaries, fallopian tubes
T13 Uterus, cervix, vagina
T14 Menstrual cycle changes or disorders
T15 Breasts, lactation (prior to or during pregnancy)
T16 Parturition
T17 Postpartum
T19 Other effects
Effects on Fertility
T21 Mating performance (e.g., number of sperm-positive females per number of females mated;
number of copulations per number of estrus cycles)
T22 Female fertility index (e.g., number of females pregnant per number of sperm-positive females;
number of females pregnant per number of females mated)
T23 Male fertility index (e.g., number of males impregnating females per number of males exposed to
fertile non-pregnant females)
T24 Pre-implantation mortality (e.g., reduction in number of implants per female; total number of
implants per corpora lutea)
T25 Post-implantation mortality (e.g., dead and/or reabsorbed implants per total number of implants)
T26 Litter size (e.g., number of fetuses per litter, measured before birth)
T27 Abortion
T29 Other measures of fertility
Effects on Embryo or Fetus
T31 Extra-embryonic structures (e.g., placenta, umbilical cord)
T32 Maternal-fetal exchange
T33 Cytological changes (including somatic cell genetic material)
T34 Fetotoxicity (except fetal death)
T35 Fetal death
T39 Other effects on embryo
Specific Developmental Abnormalities
T41 Central nervous system
T42 Eye, ear
T43 Craniofacial (including nose and tongue)
T44 Skin and skin appendages
T45 Body wall
T46 Musculoskeletal system
T47 Cardiovascular (circulatory) system
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Comprehensive Guide to RTECS
Table III. Reproductive Effects Code (Continued)
T48 Blood and lymphatic system (including spleen and marrow)
T49 Respiratory system
T50 Gastrointestinal system
T51 Hepatobiliary system
T52 Endocrine system
T53 Urogenital system
T54 Immune and reticuloendothelial system
T55 Homeostasis
T59 Other developmental abnormalities
Tumorigenic Effects
T61 Testicular tumors
T62 Prostate tumors
T63 Ovarian tumors
T64 Uterine tumors
T65 Transplacental tumorigenesis
T69 Other reproductive system tumors
Effects on Newborn
T71 Stillbirth
T72 Live birth index (similar to T26, except measured after birth)
T73 Sex ratio
T74 Apgar score (human only)
T75 Viability index (e.g., number alive at day 4 per number born alive)
T76 Weaning or lactation index (e.g., number alive at weaning per number alive at day 4)
T77 Other neonatal measures or effects
T81 Growth statistics (e.g., reduced weight gain)
T82 Germ cell effects (in offspring)
T83 Biochemical and metabolic
T84 Drug dependence
T85 Behavioral
T86 Physical
T87 Other postnatal measures or effects
T91 Delayed effects
- 50 -
December 2007
Table IV. Routes of Administration to, or Exposure of, Animal Species to Toxic Substances
Abbreviation Route Definition
eye Eyes Administration directly onto the surface of the eye. Used exclusively
for primary irritation data. See Ocular.
ial Intra-aural Administration into the ear
iat Intra-arterial Administration into the artery
ice Intracerebral Administration into the cerebrum
icv Intracervical Administration into the cervix
idr Intradermal Administration within the dermis by hypodermic needle
idu Intraduodenal Administration into the duodenum
ihl Inhalation Inhalation in chamber, by cannulation, or through mask
imp Implant Placed surgically within the body location described in reference
ims Intramuscular Administration into the muscle by hypodermic needle
ipc Intraplacental Administration into the placenta
ipl Intrapleural Administration into the pleural cavity by hypodermic needle
ipr Intraperitoneal Administration into the peritoneal cavity
irn Intrarenal Administration into the kidney
isp Intraspinal Administration into the spinal canal
itr Intratracheal Administration into the trachea
itt Intratesticular Administration into the testes
iut Intrauterine Administration into the uterus
ivg Intravaginal Administration into the vagina
ivn Intravenous Administration directly into the vein by hypodermic needle
mul Multiple Administration by more than one route
ocu Ocular Administration directly onto the surface of the eye or into the
conjunctival sac. Used exclusively for systemic toxicity data. See
Eyes.
orl Oral Per os, intragastric feeding, or introduction with drinking water
par Parenteral Administration into the body through the skin. Reference is not specific
concerning the route used.
rec Rectal Administration into the rectum or colon in the form of enema or
suppository
scu Subcutaneous Administration under the skin
skn Skin Application directly onto the skin, either intact or abraded. Used for
both systemic toxicity and primary irritant effects.
unr Unreported Dose, but not route, is specified in the reference.
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Comprehensive Guide to RTECS
Table V. Species
With assumptions for Toxic Dose Calculation from Non-specific Data*
Species Age Weight Approximate Approximate 1 ppm in Approximate
Consumption Consumption Food equals Gestation Period
of Food, of Water, in mg/kg/D (days)
gm/day mL/day
Bird, domestic or 1 kg
laboratory; bird, not
otherwise identified
Bird, wild bird 40 gm
species
Cat, adult 2 kg 100 100 0.05 64 (59 ? 68)
Child 1 ? 13 Y 20 kg
Chicken, adult (male 8W 800 gm 140 200 0.175
or female)
Cattle, horse 500 kg 10,000 0.02 284 (279 ? 290)
Duck, adult 8W 2.5 kg 250 500 0.1
(domestic)
Dog, adult 52 W 10 kg 250 500 0.025 62 (56 ? 68)
Domestic animals ? 60 kg 2,400 0.04 Goat: 152 (148-
goat, sheep 156)
Sheep: 146 (144-
147)
Frog, adult 33 gm
Guinea pig, adult 500 gm 30 85 0.06 68
Gerbil 100 gm 5 5 0.05 25 (24 ? 26)
Hamster 14 W 125 gm 15 10 0.12 16
Human Adult 70 kg
Horse, donkey 500 kg 10,000 Horse: 339 (333-
345)
Donkey: 365
Infant, human 0?1Y 5 kg
Mammal, species 200 gm
unidentified
Man Adult 70 kg
Monkey 2.5 Y 5 kg 250 500 0.05 165
Mouse 8W 25 gm 3 5 0.12 21
Non-mammalian
species
Pigeon 8W 500 gm
Pig 60 kg 2,400 0.041 114 (112 ? 115)
Quail (laboratory) 160 gm
Rat, adult female 14 W 200 gm 10 20 0.05 22
Rat, adult male 14 W 250 gm 15 25 0.06
Rat, adult, gender 14 W 200 gm 15 25
unspecified
Rat, weaning 3W 50 gm 15 25 0.3
Rabbit, adult 12 W 2 kg 60 330 0.03 31
Squirrel 500 gm 44
Toad 100 gm
Turkey 18 W 5 kg
Woman Adult 50 kg 270
*NOTE: Values given here are within reasonable limits usually found in the published literature
and are selected to facilitate calculations for data from publications in which toxic dose
information has not been presented for an individual animal of the study. Data for lifetime
exposure are calculated from the assumptions for adult animals for the entire period of exposure.
For definitive dose data, the reader must review the referenced publications.
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December 2007
Table VI. Master File Data Types (Position 10)
Code Data Type Detailed File Description
Number Format Section
A Substance Prime Name 1
B Synonym Cross Reference 1
C Chemical Description/Definition 1
D Chemical Registry Number 3
Chemical Abstracts Service
Beilstein Registry
E Update Field 2
F Molecular Formula 6
G RTECS Number 4
H Molecular Weight 5
J Wiswesser Line Notation 7
L Synonym 8
N Compound Descriptor Code 9
P Irritation Data 10, 16
Q Mutation Data 11, 16
R Reproductive Effects Data 12, 16
S Tumorigenic Data 13, 16
T Acute Toxicity Data 14, 16
U Other Multiple Dose Toxicity 15, 16
Data
V Reviews 17, 16
W Standards and Regulations 18, 16
X NIOSH REL Documentation and 19, 16
Surveillance Data
Y ATSDR, EPA, NIOSH, NTP, 20, 16
and OSHA Status
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Comprehensive Guide to RTECS
Table VII. Line Numbers for "V", "W", "X", and "Y" Data
Line Number Data
V010-039 ACGIH TLV Data
V100-299 IARC Cancer Reviews
V300 IARC Cancer Review, Supplement 7
V800-899 Toxicology Review References
W100-110 Inactive at this time
W200 EPA Farm Worker Field Re-entry Data
W400-410 MSHA Standard Data
W500 OSHA PEL (General Industry)
W505 OSHA PEL (Construction)
W510 OSHA PEL (Shipyards)
W515 OSHA PEL (Federal Contractors)
W550 OSHA Cancer Suspect Agent
W600-699 International Occupational Exposure Levels
X500-510 NIOSH REL Data
X600 NOHS (1974)
X610 NOES (21983)
Y010-035 EPA Genetic Toxicology Program Data
Y050 EPA TSCA Chemical Inventory Status 8(d)
Y100 EPA TSCA 8(a)
Y130 EPA TSCA 8(b)
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