*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : GZ4120000
CHEMICAL NAME : Cyclosporin A
CAS REGISTRY NUMBER : 59865-13-3
OTHER CAS REGISTRY NOS. : 104250-72-8
LAST UPDATED : 199801
DATA ITEMS CITED : 35
MOLECULAR FORMULA : C62-H111-N11-O12
MOLECULAR WEIGHT : 1202.84
COMPOUND DESCRIPTOR : Tumorigen
Drug
Mutagen
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* Antibiotic S 7481F1
* Ciclosporin
* Cyclosporin
* Cyclosporine
* Cyclosporine A
* OL 27-400
* Ramihyphin A
* S 7481F1
* Sandimmun
* Sandimmune
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 1911 mg/kg/91W-I
TOXIC EFFECTS :
Behavioral - convulsions or effect on seizure threshold
Behavioral - coma
Kidney, Ureter, Bladder - changes in tubules (including acute renal failure,
acute tubular necrosis)
REFERENCE :
BJRHDF British Journal of Rheumatology. (Bailliere Tindall, 33 The Avenue,
Eastborn BN21 3UN, UK) Volume(issue)/page/year: 33,90,1994
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 62500 ug/kg/5D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes
Nutritional and Gross Metabolic - body temperature increase
REFERENCE :
LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823-
Volume(issue)/page/year: 1,1221,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE/DURATION : 20 mg/kg/2D-I
TOXIC EFFECTS :
Behavioral - headache
Vascular - acute arterial occlusion
Lungs, Thorax, or Respiration - cyanosis
REFERENCE :
LANCAO Lancet. (7 Adam St., London WC2N 6AD, UK) V.1- 1823-
Volume(issue)/page/year: 2,1092,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human
DOSE/DURATION : 12 mg/kg
TOXIC EFFECTS :
Vascular - BP elevation not characterized in autonomic section
Endocrine - antidiuresis
REFERENCE :
JOHYD3 Journal of Hypertension. (Current Science, 1201 Locust St.,
Philadelphia, PA 19107) V.1- 1983- Volume(issue)/page/year:
11,1209,1993
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Unreported
SPECIES OBSERVED : Human - man
DOSE/DURATION : 30 mg/kg/4D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in tubules (including acute renal failure,
acute tubular necrosis)
REFERENCE :
AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200
Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year:
107,786,1987
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 1480 mg/kg
TOXIC EFFECTS :
Behavioral - muscle contraction or spasticity
Gastrointestinal - hypermotility, diarrhea
Skin and Appendages - hair
REFERENCE :
ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000
Berlin 33, Fed. Rep. Ger.) V.32- 1974- Volume(issue)/page/year:
53,107,1983
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 147 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho
Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970-
Volume(issue)/page/year: 17,365,1986
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 286 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho
Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970-
Volume(issue)/page/year: 17,365,1986
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 24 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho
Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970-
Volume(issue)/page/year: 17,365,1986
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 2329 mg/kg
TOXIC EFFECTS :
Behavioral - muscle contraction or spasticity
Gastrointestinal - hypermotility, diarrhea
Skin and Appendages - hair
REFERENCE :
ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000
Berlin 33, Fed. Rep. Ger.) V.32- 1974- Volume(issue)/page/year:
53,107,1983
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 96 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho
Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970-
Volume(issue)/page/year: 17,365,1986
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE/DURATION : >1 gm/kg
TOXIC EFFECTS :
Behavioral - muscle contraction or spasticity
Gastrointestinal - hypermotility, diarrhea
Skin and Appendages - hair
REFERENCE :
ARTODN Archives of Toxicology. (Springer-Verlag, Heidelberger Pl. 3, D-1000
Berlin 33, Fed. Rep. Ger.) V.32- 1974- Volume(issue)/page/year:
53,107,1983
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rabbit
DOSE/DURATION : 10 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
TOPADD Toxicologic Pathology. (c/o Dr. F.A. de la Iglesia, Warner-Lambert
Co., Pharmaceutical Research Div., POB 1047, Ann Arbor, MI 48106) V.6(3/4)-
1978- Volume(issue)/page/year: 14,73,1986
** 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/14D-I
TOXIC EFFECTS :
Endocrine - changes in spleen weight
Blood - changes in spleen
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year:
39,53,1997
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 350 mg/kg/7D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes in urine composition
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
Biochemical - Enzyme inhibition, induction, or change in blood or tissue
levels - multiple enzyme effects
REFERENCE :
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1977- Volume(issue)/page/year: 32,163,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 800 mg/kg/10D-I
TOXIC EFFECTS :
Behavioral - food intake (animal)
Nutritional and Gross Metabolic - weight loss or decreased weight gain
Related to Chronic Data - death
REFERENCE :
TRPPA8 Transplantation Proceedings. (Appleton & Lange, 25 Van Zant St.,
East Norwalk, CT 06855) V.1- 1969- Volume(issue)/page/year: 24(Suppl
2),39,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 420 mg/kg/28D-I
TOXIC EFFECTS :
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
Musculoskeletal - other changes
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 : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 700 mg/kg/28D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - changes in tubules (including acute renal failure,
acute tubular necrosis)
Kidney, Ureter, Bladder - other changes in urine composition
REFERENCE :
KBPRFC Kidney & Blood Pressure Research. (S. Karger Publishers, POB 529,
Farmington, CT 06085) V.19- 1996- Volume(issue)/page/year: 20,38,1997
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 210 mg/kg/14D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - renal function tests depressed
Kidney, Ureter, Bladder - other changes in urine composition
Biochemical - Enzyme inhibition, induction, or change in blood or tissue
levels - other transferases
REFERENCE :
TOLED5 Toxicology Letters. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1977- Volume(issue)/page/year: 58,169,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 1200 mg/kg/40D-I
TOXIC EFFECTS :
Kidney, Ureter, Bladder - other changes in urine composition
Biochemical - Metabolism (Intermediary) - amino acids (including renal
excretion)
Biochemical - Metabolism (Intermediary) - Plasma proteins not involving
coagulation
REFERENCE :
EXMPA6 Experimental and Molecular Pathology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1962- Volume(issue)/page/year:
55,83,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 140 mg/kg/7D-I
TOXIC EFFECTS :
Vascular - BP elevation not characterized in autonomic section
Vascular - regional or general arteriolar or venous dilation
REFERENCE :
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams &
Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
Volume(issue)/page/year: 259,905,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intravenous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 60 mg/kg/3D-I
TOXIC EFFECTS :
Vascular - BP elevation not characterized in autonomic section
Vascular - structural changes in vessels
Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
REFERENCE :
JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams &
Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10-
Volume(issue)/page/year: 259,905,1991
** TUMORIGENIC DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - man
DOSE/DURATION : 259 mg/kg/2W-C
TOXIC EFFECTS :
Tumorigenic - Carcinogenic by RTECS criteria
Blood - lymphoma, including Hodgkin's disease
REFERENCE :
CEDEDE Clinical and Experimental Dermatology. (Blackwell Scientific Pub.
Ltd., POB 88, Oxford, UK) V.1- 1976- Volume(issue)/page/year: 8,159,1983
** REPRODUCTIVE DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 166 mg/kg
SEX/DURATION : male 45 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
Reproductive - Paternal Effects - other effects on male
Reproductive - Fertility - male fertility index (e.g. # males impregnating
females per # males exposed to fertile nonpregnant females)
REFERENCE :
JOAND3 Journal of Andrology. (Lippincott/Harper, Journal Fulfillment Dept.,
2350 Virginia Ave., Hagerstown, MD 21740) V.1- 1980-
Volume(issue)/page/year: 11,17,1990
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE : 420 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 : 560 mg/kg
SEX/DURATION : male 14 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Paternal Effects - spermatogenesis (incl. genetic material,
sperm morphology, motility, and count)
Reproductive - Paternal Effects - testes, epididymis, sperm duct
Reproductive - Paternal Effects - other effects on male
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: 82,1059,1991
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE : 90 mg/kg
SEX/DURATION : female 6-8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
Reproductive - Effects on Embryo or Fetus - fetal death
REFERENCE :
BNEOBV Biology of the Neonate. (S. Karger Pub., Inc., 79 Fifth Ave., New
York, NY 10003) V.15- 1970- Volume(issue)/page/year: 56,165,1989
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE : 50 mg/kg
SEX/DURATION : female 12 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
Reproductive - Specific Developmental Abnormalities - craniofacial
(including nose and tongue)
REFERENCE :
JCGBDF Journal of Craniofacial Genetics and Developmental Biology. (Alan R.
Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1980-
Volume(issue)/page/year: 12,155,1992
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intramuscular
SPECIES OBSERVED : Rodent - rabbit
DOSE : 210 mg/kg
SEX/DURATION : female 14 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Maternal Effects - ovaries, fallopian tubes
Reproductive - Fertility - other measures of fertility
REFERENCE :
INJFA3 International Journal of Fertility. (Allen Press, 1041 New
Hampshire, St., Lawrence, KS 66044) V.1- 1955- Volume(issue)/page/year:
29,218,1984
** MUTATION DATA **
TYPE OF TEST : Mutation test systems - not otherwise specified
TEST SYSTEM : Human Lymphocyte
DOSE/DURATION : 50 mg/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 320,217,1994
TYPE OF TEST : Sister chromatid exchange
TEST SYSTEM : Human Lymphocyte
DOSE/DURATION : 1 mg/L
REFERENCE :
IGAYAY Igaku No Ayumi. Progress in Medicine. (Ishiyaku Shuppan K.K.,
1-7-10, Honkomagom, Bunkyo-ku, Tokyo, Japan) V.1- 1946-
Volume(issue)/page/year: 134,403,1985
*** REVIEWS ***
IARC Cancer Review:Human Sufficient Evidence
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals
to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210)
V.1- 1972- Volume(issue)/page/year: 50,77,1990
IARC Cancer Review:Animal Limited Evidence
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals
to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210)
V.1- 1972- Volume(issue)/page/year: 50,77,1990
IARC Cancer Review:Group 1
IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals
to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210)
V.1- 1972- Volume(issue)/page/year: 50,77,1990
*** STATUS IN U.S. ***
NTP Carcinogenesis studies; on test (prechronic studies), October 1997
*** END OF RECORD ***