RTECS NUMBER : KD4200000
CHEMICAL NAME : 15,19-Epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclotricosine
-1,7,20,21(4H,23H)-te trone,
5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadec
ahydro-5,19-dihydroxy -3-(2-(4-hydroxy-3-
methoxycyclohexyl)-14,16-dimethoxy-4,10,12,18-tetrame
thyl-8-(2-propenyl)-,
(3S-(3R*(E(1S*,3S*,4S*)),4S*,5R*,8S*,9E,12R*,14R*,15S
*,16R*,18S*,19S*,26aR *))-
CAS REGISTRY NUMBER : 104987-11-3
LAST UPDATED : 199612
DATA ITEMS CITED : 12
MOLECULAR FORMULA : C44-H69-N-O12
MOLECULAR WEIGHT : 804.14
COMPOUND DESCRIPTOR : Drug
Reproductive Effector
Natural Product
SYNONYMS/TRADE NAMES :
* FK 506
* FR 900506
* Prograf
* Tacrolimus
* Tsukubaenolide
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >200 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8
Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968-
Volume(issue)/page/year: 40,1249,1987
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 140 mg/kg/28D-I
TOXIC EFFECTS :
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
Musculoskeletal - other changes
Nutritional and Gross Metabolic - changes in calcium
REFERENCE :
TRPLAU Transplantation. (Williams & Wilkins, Co., 428 E. Preston St.,
Baltimore, MD 21202) V.1- 1963- Volume(issue)/page/year: 57,1231,1994
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 52500 ug/kg/21D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes in urine composition
Kidney, Ureter, Bladder - changes in bladder weight
REFERENCE :
NGKZA6 Nippon Hinyokika Gakkai Zasshi. Japanese Journal of Urology.
(Japanese Urological Association, c/o Dept. of Urology, Faculty of Medicine,
University of Tokyo, 7-3-1 Bunkyo-ku, Tokyo 113 Japan) V.1- 1917-
Volume(issue)/page/year: 83,650,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 140 mg/kg/14D-I
TOXIC EFFECTS :
Gastrointestinal - changes in structure or function of endocrine pancreas
Endocrine - hyperglycemia
REFERENCE :
JTSCDR Journal of Toxicological Sciences. (Japanese Soc. of Toxicological
Sciences, 4th Floor, Gakkai Center Bldg., 4-16, Yayoi 2-chome, Bunkyo-ku,
Tokyo 113, Japan) V.1- 1976- Volume(issue)/page/year: 19,61,1994
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 547 mg/kg/52W-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes in urine composition
Blood - changes in erythrocyte (RBC) count
Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 26,953,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Primate - monkey
DOSE/DURATION : 3650 mg/kg/52W-I
TOXIC EFFECTS :
Blood - changes in erythrocyte (RBC) count
Nutritional and Gross Metabolic - weight loss or decreased weight gain
Nutritional and Gross Metabolic - changes in chlorine
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 26,3129,1992
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 368 mg/kg
SEX/DURATION : male 60 day(s) pre-mating
female 2 week(s) pre-mating - 3 week(s) post-birth
TOXIC EFFECTS :
Reproductive - Fertility - pre-implantation mortality (e.g. reduction in
number of implants per female; total number of implants per corpora lutea)
Reproductive - Effects on Newborn - live birth index (measured after birth)
Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4
per # born alive)
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 26,969,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 11 mg/kg
SEX/DURATION : female 7-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Paternal Effects - other effects on male
Reproductive - Fertility - female fertility index (e.g. # females pregnant
per # sperm positive females; # females pregnant per # females mated)
Reproductive - Effects on Embryo or Fetus - other effects to embryo
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 26,969,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 14 mg/kg
SEX/DURATION : male 14 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
REFERENCE :
TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85,
Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 109,75,1996
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 42 mg/kg
SEX/DURATION : male 14 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetal death
REFERENCE :
TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85,
Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 109,75,1996
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Rodent - mouse
DOSE : 2720 ug/kg
SEX/DURATION : female 1-16 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
REFERENCE :
TRPLAU Transplantation. (Williams & Wilkins, Co., 428 E. Preston St.,
Baltimore, MD 21202) V.1- 1963- Volume(issue)/page/year: 52(1),106,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 13 mg/kg
SEX/DURATION : female 6-18 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured
before birth)
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda
Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960-
Volume(issue)/page/year: 26,969,1992
*** END OF RECORD ***
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