Atomoxetine Hydrochloride Tablets and Capsules                                             Page 1 of 9









                                           Atomoxetine Hydrochloride

                                              Tablets and Capsules

Eli Lilly and Company                                  Effective Date: 08-Jan-2005

Material Safety Data Sheet





                 Section 1 - Chemical Product and Company

                                                   Manufacturer's Emergency Phone:

Manufacturer:

                                                   1-317-276-2000

Eli Lilly and Company

                                                   CHEMTREC:

Lilly Corporate Center

                                                   1-800-424-9300 (North America)

Indianapolis, IN 46285

                                                   1-703-527-3887 (International)



Common Name: Atomoxetine Hydrochloride Tablets and Capsules



Chemical Name: Benzenepropanamine, N-methyl-gamma-(2-methylphenoxy)-, hydrochloride,

(gammaR)-

Chemical Name 2: (-)-N-Methyl-3-phenyl-3-(ortho-tolyloxy)-propylamine hydrochloride

Synonym(s): 139603 Formulation; Tomoxetine; Tomoxetine hydrochloride capsules and tablets;

Tomoxetine hydrochloride formulation; Tomoxetine hydrochloride high dose tablets and capsules;

Tomoxetine hydrochloride tablets and capsules

Trademarks(s): Atenten; Atentin; Atinten; Cerentra; Compedur; Noriqual; Strattera; Valindra; Xovene

Lilly Item Code(s): B02453; B02455; B02457; B02459; B02490; ND1061; ND1062; ND1063;

ND1064; ND1090; ND1101; ND1102; ND1103; ND1104; PU3225; PU3226; PU3227; PU3228;

PU3229; PU3238; PU3239; PU3250; PU3251; TA4705; TA4710; TA4725; TA4740; UC9546;

UC9547; UC9548; UC9549; UC9550



See attached glossary for abbreviations.





          Section 2 - Composition / Information on Ingredients

Ingredient                                            CAS       Concentration %

Atomoxetine Hydrochloride                       82248-59-7           2 - 33

Excipients                                             NA           71 - 98



Contains no hazardous components (one percent or greater) or carcinogens (one-tenth percent or

greater) not listed above.



Exposure Guidelines:

Atomoxetine hydrochloride - LEG 25 micrograms/m3 TWA for 12 hours. LEG 38 micrograms/m3

TWA for 8 hours.





                         Section 3 - Hazards Identification





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Appearance: White to off-white powder finished as capsules or tablets

Physical State: Solid

Odor: Odorless







 Emergency Overview

 Emergency Overview Effective Date: 04-Apr-2001



 Lilly Laboratory Labeling Codes:

 Health 3               Fire 1                      Reactivity 0



 Primary Physical and Health Hazards: Not hazardous if intact. Corrosive (eyes). Nervous System

 and Heart Effects.



 Caution Statement: Intact Atomoxetine Hydrochloride Tablets and Capsules are not considered to

 be a health hazard. The contents of Atomoxetine Hydrochloride Tablets and Capsules may cause

 burns or permanent tissue damage to the eyes. Effects of exposure may include tremors, nervousness,

 anxiety, nausea, headache, change in blood pressure, and increased heart rate.





Routes of Entry: Inhalation and skin contact.



Effects of Overexposure: Tablets and capsules are intended for human consumption under guidance of

a physician. Based on animal/clinical data, atomoxetine hydrochloride may be harmful if ingested, may

be fatal if inhaled, may cause burns or permanent tissue damage to the eyes, and is not expected to be

irritating to the skin. Effects of overexposure to atomoxetine hydrochloride may include gastrointestinal

effects (nausea, vomiting), fatigue, decreased appetite, dizziness, mood swings, insomnia, and increased

blood pressure and heart rate. Rare cases of liver toxicity have been reported. Animal studies with

atomoxetine hydrochloride have reported liver effects, dilated pupils, and tremors.



Medical Conditions Aggravated by Exposure:

Atomoxetine hydrochloride - Individuals with cardiovascular disease, glaucoma, or on monoamine

oxidase inhibitor (MAOI) therapy.



Carcinogenicity:

Atomoxetine hydrochloride - Not listed by IARC, NTP, ACGIH, or OSHA.





                            Section 4 - First Aid Measures

Eyes: Hold eyelids open and flush with a steady, gentle stream of water for 15 minutes. See an

ophthalmologist (eye doctor) or other physician immediately. Immediate rinsing may prevent

permanent damage.



Skin: Remove contaminated clothing and clean before reuse. Wash all exposed areas of skin with

plenty of soap and water. Get medical attention if irritation develops.









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Inhalation: Move individual to fresh air. Get medical attention if breathing difficulty occurs. If not

breathing, provide artificial respiration assistance (mouth-to-mouth) and call a physician immediately.



Ingestion: Do not induce vomiting. Call a physician or poison control center. If available, administer

activated charcoal (6-8 heaping teaspoons) with two to three glasses of water. Do not give anything by

mouth to an unconscious person. Immediately transport to a medical care facility and see a physician.



Notes to Physician:

Atomoxetine - An airway should be established. Monitoring of cardiac and vital signs is recommended,

along with appropriate symptomatic and supportive measures. Gastric lavage may be indicated if

performed soon after ingestion. Because atomoxetine is highly protein-bound, dialysis is not likely to

be useful in the treatment of overdose.





                         Section 5 - Fire Fighting Measures

Flash Point: Not applicable

UEL: No applicable information found

LEL: No applicable information found



Extinguishing Media: Use water, carbon dioxide, dry chemical, foam, or Halon.



Unusual Fire and Explosion Hazards: As a finely divided material, may form dust mixtures in air

which could explode if subjected to an ignition source.



Hazardous Combustion Products: May emit toxic chloride fumes when exposed to heat or fire.





                    Section 6 - Accidental Release Measures

The following are recommended for manufacturing or other situations where exposure to the capsule

contents or tablet powder may occur.



Spills: Vacuum material with appropriate dust collection filter in place. Be aware of potential for dust

explosion when using electrical equipment. If vacuum is not available, lightly mist material and remove

by sweeping or wet wiping. Wear protective equipment, including eye protection, to avoid exposure

(see Section 8 for specific handling precautions).





                          Section 7 - Handling and Storage

Storage Conditions: Controlled Room Temperature: 15 to 30 C (59 to 86 F).





           Section 8 - Exposure Controls / Personal Protection

See Section 2 for Exposure Guideline information.



Intact capsules and coated compressed tablets are not considered hazardous under normal handling

procedures and protective equipment is not required. The following are recommended for







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manufacturing or other situations where exposure to the capsule contents or tablet powder may occur.



Respiratory Protection: Use an approved respirator.



Eye Protection: Chemical goggles and/or face shield.



Ventilation: Laboratory fume hood or local exhaust ventilation.



Other Protective Equipment: Chemical-resistant gloves and body covering to minimize skin

contact. If handled in a ventilated enclosure, as in a laboratory setting, respirator and goggles or face

shield may not be required. Safety glasses are always required.



Additional Exposure Precautions: In production settings, airline-supplied, hood-type respirators are

preferred. Shower and change clothing if skin contact occurs.





                 Section 9 - Physical and Chemical Properties

Appearance: White to off-white powder finished as capsules or tablets

Odor: Odorless

Boiling Point: No applicable information found

Melting Point: No applicable information found

Density: No applicable information found

pH: No applicable information found

Evaporation Rate: No applicable information found

Water Solubility: Soluble

Vapor Density: No applicable information found

Vapor Pressure: No applicable information found





                        Section 10 - Stability and Reactivity

Stability: Stable at normal temperatures and pressures.



Incompatibility: May react with strong oxidizing agents (e.g., peroxides, permanganates, nitric acid,

etc.).



Hazardous Decomposition: May emit toxic chloride fumes when heated to decomposition.



Hazardous Polymerization: Will not occur.





                      Section 11 - Toxicological Information



Acute Exposure

Oral:

Atomoxetine hydrochloride - Rat (fasted), median lethal dose 196 mg/kg.

Rat (fed), median lethal dose estimated greater than 300 mg/kg, mortality, myoclonic jerking.









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Dog, 37.5 mg/kg, no deaths, tremors, myoclonic jerking, dilation of the pupils.



Skin:

Atomoxetine hydrochloride - Rabbit, 200 mg/kg, no deaths or toxicity.



Inhalation:

Atomoxetine hydrochloride (racemic mixture) - Rat, median lethal concentration 330 mg/m3 for 4

hours.

Atomoxetine hydrochloride tablets and capsules formulation - The formulated material is not expected

to pose an inhalation hazard.



Skin Contact:

Atomoxetine hydrochloride - Rabbit, nonirritant



Eye Contact:

Atomoxetine hydrochloride - Rabbit, corrosive

(Injury was decreased if eyes were rinsed immediately after exposure)



Chronic Exposure

Target Organ Effects:

Atomoxetine hydrochloride - Hepatotoxicity (increased liver weight, hepatocellular vacuolation,

increased serum ALT) was reported in male rats given dietary concentrations greater than or equal to

0.01% for 3 or 12 months and in mice given 0.4% in diet for 3 months. No hepatoxicity was observed

in dogs administered up to 16 mg/kg/day for 3 or 12 months. Clinical signs (pupillary light response,

tremors, dilated pupils) were observed in dogs given less than 8 mg/kg/day for 1 year. Young rats

administered up to 50 mg/kg/day from 10 days of age through adulthood matured physically and

behaviorally with no major organ toxicity.



Reproduction:

Atomoxetine hydrochloride - Slight fertility effects reported in a 1-generation fertility study in

rats. However, fertility findings were not duplicated in a subsequent 2-generation study at equivalent

doses and route of administration. Embryo-fetal developmental toxicity studies in rats and rabbits

indicate that atomoxetine is not teratogenic or embryotoxic. Study results indicate that atomoxetine

administered to young rats causes a slight delay in puberty and in epididymal sperm counts but that

these effects have no impact on reproduction.



Sensitization: No applicable information found.



Mutagenicity:

Atomoxetine hydrochloride - Negative in Ames, unscheduled DNA synthesis, sister chromatid

exchange, chromosome aberration, mouse micronucleus, mouse lymphoma, and mouse micronucleus

(in vivo) assays.



Carcinogenicity:

Atomoxetine hydrochloride - No evidence of carcinogenicity reported in two-year studies at dietary

concentrations up to 0.1% (rats) and 0.3% (mice).





                        Section 12 - Ecological Information





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No environmental data for the mixture or formulation. The environmental information for ingredient(s)

or related material(s) are presented.



Ecotoxicity Data:

Atomoxetine Hydrochloride

Rainbow trout 96-hour median lethal concentration: 3.2 mg/L

Daphnia magna 48-hour median effective concentration: 4.7 mg/L

Daphnia magna 21-day chronic median effective concentration: 1.7 mg/L

Green algae (S.capricornutum) 72-hour median effective concentration: 1.23 mg/L

Green algae (P.subcapitata) 72-hour median effective concentration (biomass): 0.42 mg/L

Activated sludge respiration inhibition - 3-hour median effective concentration (1.4 g solids/L): 138

Activated sludge respiration inhibition - 3-hour median effective concentration (1.6 g solids/L): 73.1

mg/L



Environmental Fate:

Atomoxetine Hydrochloride

Log Kow: 0.104, 0.676, 2.81 (pH 4, 7, 9)

Bioconcentration factor (calculated from Log Kow at pH 9): 113

pKa: 9.23

Biodegradation half-life in municipal sewage sludge (1.4 g solid/L): none measured

Municipal sewage sludge Kd (1.4 g total suspended solids/L): 540

Sludge adsorption (Koc): 533, 452, 488, and 794 (2500, 1250, 625, and 313 mg solids/L

Sludge biodegradation half-life: 136 hours

Photolysis: 0% loss at pH 4, 7, and 9

Hydrolysis: < 10% over 5 days.



Environmental Summary:

Atomoxetine hydrochloride - Material is highly toxic to green algae, moderately toxic to aquatic

invertebrates and fish, and is practically non-toxic to activated sludge microorganisms. Measurable

concentrations in the atmosphere are not expected since it is a non-volatile solid. The solubility of the

material in water is high. The atomoxetine concentration in activated municipal sludge declined after 24

hours primarily due to sorption with very little loss attributed to biodegradation. Material will not

bioconcentrate in aquatic organisms.



Lilly Aquatic Exposure Guideline (LAEG):

Atomoxetine hydrochloride

LAEG for Drinking Water: 12.5 micrograms/L

LAEG for Chronic Exposure of Aquatic Organisms: 14 micrograms/L

LAEG for Acute Exposure of Aquatic Organisms: 120 micrograms/L





                       Section 13 - Disposal Considerations

Waste Disposal: Dispose of any cleanup materials and waste residue according to all applicable laws

and regulations.





                        Section 14 - Transport Information

Regulatory Organizations:









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DOT: Not Regulated



ICAO/IATA: Not Regulated



IMO: Not Regulated





                       Section 15 - Regulatory Information

Below is selected regulatory information chosen primarily for possible Eli Lilly and Company

usage. This section is not a complete analysis or reference to all applicable regulatory

information. Please consider all applicable laws and regulations for your country/state.



U.S. Regulations

Atomoxetine hydrochloride

TSCA - No

CERCLA - Not on this list

SARA 302 - Not on this list

SARA 313 - Not on this list

OSHA Substance Specific - No



EU Regulations

EC Classification

Xn (Harmful)

Xi (Irritant)

N (Dangerous for the Environment)



Risk Phrases

R 22 - Harmful if swallowed.

R 41 - Risk of serious damage to eyes.

R 50 - Very toxic to aquatic organisms.



Safety Phrases

S 26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.

S 36/37/39 - Wear suitable protective clothing, gloves and eye/face protection.

S 45 - In case of accident or if you feel unwell, seek medical advice immediately (show the label where

possible).





                            Section 16 - Other Information

MSDS Sections Revised: Section 1.



As of the date of issuance, we are providing available information relevant to the handling of this

material in the workplace. All information contained herein is offered with the good faith belief that it

is accurate. THIS MATERIAL SAFETY DATA SHEET SHALL NOT BE DEEMED TO CREATE

ANY WARRANTY OF ANY KIND (INCLUDING WARRANTY OF MERCHANTABILITY OR

FITNESS FOR A PARTICULAR PURPOSE). In the event of an adverse incident associated with this







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material, this safety data sheet is not intended to be a substitute for consultation with appropriately

trained personnel. Nor is this safety data sheet intended to be a substitute for product literature which

may accompany the finished product.



For additional information contact:

Eli Lilly and Company

Hazard Communication

317-277-6029





GLOSSARY:



ACGIH = American Conference of Governmental Industrial Hygienists

AIHA = American Industrial Hygiene Association

BEI = Biological Exposure Index

CAS Number = Chemical Abstract Service Registry Number

CERCLA = Comprehensive Environmental Response Compensation and Liability Act (of 1980)

CHAN = Chemical Hazard Alert Notice

CHEMTREC = Chemical Transportation Emergency Center

DOT = Department of Transportation

EC = European Community

EINECS = European Inventory of Existing Chemical Substances

ELINCS = European List of New Chemical Substances

EPA = Environmental Protection Agency

HEPA = High Efficiency Particulate Air (Filter)

IARC = International Agency for Research on Cancer

ICAO/IATA = International Civil Aviation Organization/International Air Transport Association

IEG = Lilly Interim Exposure Guideline

IMO = International Maritime Organization

Kow = Octanol/Water Partition Coefficient

LEG = Lilly Exposure Guideline

LEL = Lower Explosive Limit

MSDS = Material Safety Data Sheet

MSHA = Mine Safety and Health Administration

NA = Not Applicable, except in Section 14 where NA = North America

NADA = New Animal Drug Application

NAIF = No Applicable Information Found

NCI = National Cancer Institute

NIOSH = National Institute for Occupational Safety and Health

NOS = Not Otherwise Specified

NTP = National Toxicology Program

OSHA = Occupational Safety and Health Administration

PEL = Permissible Exposure Limit (OSHA)

RCRA = Resource Conservation and Recovery Act

RQ = Reportable Quantity

RTECS = Registry of Toxic Effects of Chemical Substances

SARA = Superfund Amendments and Reauthorization Act

STEG = Lilly Short Term Exposure Guideline

STEL = Short Term Exposure Limit

TLV = Threshold Limit Value (ACGIH)

TPQ = Threshold Planning Quantity







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TSCA = Toxic Substances Control Act

TWA = Time Weighted Average/8 Hours Unless Otherwise Noted

UEL = Upper Explosive Limit

UN = United Nations

WEEL = Workplace Environmental Exposure Level (AIHA)









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