*** CHEMICAL IDENTIFICATION ***
RTECS NUMBER : RA6620000
CHEMICAL NAME : 2,4,6,8-Nonanetetraenoic acid,
9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-,
ethyl ester, all-trans-
CAS REGISTRY NUMBER : 54350-48-0
LAST UPDATED : 199801
DATA ITEMS CITED : 31
MOLECULAR FORMULA : C23-H30-O3
MOLECULAR WEIGHT : 354.53
WISWESSER LINE NOTATION : 2OV1UY1&1U1Y1&U2U1R B1 C1 F1 DO1
COMPOUND DESCRIPTOR : Mutagen
Reproductive Effector
Human
SYNONYMS/TRADE NAMES :
* 3,7-Dimethyl-9-(4-methoxy-2,3,6-trimethylphenyl)-2,4,6,8-nonanetetraenoic
acid ethyl ester
* Ethyl
all-trans-9-(4-methoxy-2,3,6-trimethylphenyl)-3,7-dimethyl-2,4,6,8-nonat
etraenoate
* Ethyl etrinoate
* Etretinate
* Ro 10-9359
* Tigason
*** HEALTH HAZARD DATA ***
** ACUTE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human
DOSE/DURATION : 78 mg/kg/26W-I
TOXIC EFFECTS :
Skin and Appendages - dermatitis, other (after systemic exposure)
Skin and Appendages - hair
Skin and Appendages - nails
REFERENCE :
ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag,
Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951-
Volume(issue)/page/year: 32,842,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 60 mg/kg/17W-I
TOXIC EFFECTS :
Skin and Appendages - hair
REFERENCE :
CUTIBC CUTIS; Cutaneous Medicine for the Practitioner. (Technical Pub., 875
Third Ave., New York, NY NY 10022) 1965- Volume(issue)/page/year:
35,466,1985
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Human - woman
DOSE/DURATION : 80 ug/kg/8D-I
TOXIC EFFECTS :
Liver - other changes
Skin and Appendages - dermatitis, other (after systemic exposure)
Nutritional and Gross Metabolic - body temperature increase
REFERENCE :
BJDEAZ British Journal of Dermatology. (Blackwell Scientific Pub. Ltd., POB
88, Oxford, UK) V.63- 1951- Volume(issue)/page/year: 112,373,1985
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >4 gm/kg
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Gastrointestinal - hypermotility, diarrhea
Skin and Appendages - hair
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu
Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972-
Volume(issue)/page/year: 10,5033,1982
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >1 gm/kg
TOXIC EFFECTS :
Skin and Appendages - hair
Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu
Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972-
Volume(issue)/page/year: 10,5033,1982
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : >1 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu
Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972-
Volume(issue)/page/year: 10,5033,1982
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >2 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
JAADDB Journal of the American Academy of Dermatology. (C.V. Mosby Co.,
11830 Westline Industrial Dr., St. Louis, MO 63141) 1979-
Volume(issue)/page/year: 6,652,1982
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : 1 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
USXXAM United States Patent Document. (U.S. Patent Office, Box 9,
Washington, DC 20231) Volume(issue)/page/year: #4105681
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Subcutaneous
SPECIES OBSERVED : Rodent - mouse
DOSE/DURATION : >1 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo,
Japan) Volume(issue)/page/year: -,191,1990
TYPE OF TEST : LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE/DURATION : >2 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
JAADDB Journal of the American Academy of Dermatology. (C.V. Mosby Co.,
11830 Westline Industrial Dr., St. Louis, MO 63141) 1979-
Volume(issue)/page/year: 6,652,1982
** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 2478 mg/kg/2W-I
TOXIC EFFECTS :
Behavioral - somnolence (general depressed activity)
Nutritional and Gross Metabolic - weight loss or decreased weight gain
REFERENCE :
YHHPAL Yaoxue Xuebao. Acta Pharmaceutica Sinica. Pharmaceutical Journal.
(China International Book Trading Corp., POB 2820, Beijing, Peop. Rep.
China) V.1- 1953- Suspended 1966-78. Volume(issue)/page/year:
17,331,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE/DURATION : 700 mg/kg/5W-I
TOXIC EFFECTS :
Musculoskeletal - changes in teeth and supporting structures
Nutritional and Gross Metabolic - weight loss or decreased weight gain
Related to Chronic Data - death
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu
Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972-
Volume(issue)/page/year: 10,5045,1982
** REPRODUCTIVE DATA **
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 - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu
Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972-
Volume(issue)/page/year: 10,5095,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 25 mg/kg
SEX/DURATION : female 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 - fetotoxicity (except death,
e.g., stunted fetus)
Reproductive - Effects on Embryo or Fetus - other effects to embryo
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan
R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
Volume(issue)/page/year: 42,25,1990
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 40 mg/kg
SEX/DURATION : female 1 day(s) pre-mating
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - eye/ear
Reproductive - Specific Developmental Abnormalities - skin and skin
appendages
Reproductive - Specific Developmental Abnormalities - urogenital system
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu
Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972-
Volume(issue)/page/year: 10,5117,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 88 mg/kg
SEX/DURATION : female 7-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - gastrointestinal
system
Reproductive - Specific Developmental Abnormalities - urogenital system
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu
Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972-
Volume(issue)/page/year: 10,5095,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rat
DOSE : 44 mg/kg
SEX/DURATION : female 7-17 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - craniofacial
(including nose and tongue)
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu
Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972-
Volume(issue)/page/year: 10,5095,1982
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE : 10 mg/kg
SEX/DURATION : female 8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - craniofacial
(including nose and tongue)
REFERENCE :
SJPSEM Scandinavian Journal of Plastic and Reconstructive Surgery and Hand
Surgery. (Almgvist & Wiksell, POB 638, S-10128 Stockholm, Sweden) V.21-
1987- Volume(issue)/page/year: 24,3,1990
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Intraperitoneal
SPECIES OBSERVED : Rodent - rat
DOSE : 10 mg/kg
SEX/DURATION : female 8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - eye/ear
Reproductive - Specific Developmental Abnormalities - craniofacial
(including nose and tongue)
REFERENCE :
ORLJAH ORL. Journal for Oto-Rhino-Laryngology and Its Related Specialties,
(S.Karger Publishers, POB 529, Farmington, CT 06085) V.34- 1972-
Volume(issue)/page/year: 59,147,1997
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 40 mg/kg
SEX/DURATION : female 7-16 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - craniofacial
(including nose and tongue)
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
Reproductive - Effects on Newborn - stillbirth
REFERENCE :
46IZA7 "Retinoids, Advances in Basic Research and Therapy, Proceedings of
the International Dermatology Symposium, Berlin, 1980," Orfanos, C.E., et
al., eds., New York, Springer-Verlag, 1981 Volume(issue)/page/year:
-,49,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 80 mg/kg
SEX/DURATION : female 7-16 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetal death
REFERENCE :
46IZA7 "Retinoids, Advances in Basic Research and Therapy, Proceedings of
the International Dermatology Symposium, Berlin, 1980," Orfanos, C.E., et
al., eds., New York, Springer-Verlag, 1981 Volume(issue)/page/year:
-,49,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 100 mg/kg
SEX/DURATION : female 11 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - other developmental
abnormalities
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan
R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
Volume(issue)/page/year: 34,412,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - mouse
DOSE : 15 mg/kg
SEX/DURATION : female 7 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - cardiovascular
(circulatory) system
Reproductive - Specific Developmental Abnormalities - other developmental
abnormalities
REFERENCE :
JKMSEH Journal of Korean Medical Science. (Korean Academy of Medical
Science, C.P.O. Box 2062, Seoul, S. Korea) V.1- 1986-
Volume(issue)/page/year: 10,250,1995
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Implant
SPECIES OBSERVED : Rodent - mouse
DOSE : 27500 ug/kg
SEX/DURATION : female 8-14 day(s) after conception
TOXIC EFFECTS :
Reproductive - Specific Developmental Abnormalities - craniofacial
(including nose and tongue)
Reproductive - Specific Developmental Abnormalities - musculoskeletal system
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan
R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
Volume(issue)/page/year: 34,420,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Implant
SPECIES OBSERVED : Rodent - mouse
DOSE : 336 mg/kg
SEX/DURATION : female 8-14 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetal death
REFERENCE :
TJADAB Teratology, The International Journal of Abnormal Development. (Alan
R. Liss, Inc., 41 E. 11th St., New York, NY 10003) V.1- 1968-
Volume(issue)/page/year: 34,420,1986
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - rabbit
DOSE : 26 mg/kg
SEX/DURATION : female 7-19 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
REFERENCE :
46IZA7 "Retinoids, Advances in Basic Research and Therapy, Proceedings of
the International Dermatology Symposium, Berlin, 1980," Orfanos, C.E., et
al., eds., New York, Springer-Verlag, 1981 Volume(issue)/page/year:
-,49,1981
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - hamster
DOSE : 44 mg/kg
SEX/DURATION : female 8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death,
e.g., stunted fetus)
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year:
4,977,1984
TYPE OF TEST : TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE : Oral
SPECIES OBSERVED : Rodent - hamster
DOSE : 88 mg/kg
SEX/DURATION : female 8 day(s) after conception
TOXIC EFFECTS :
Reproductive - Fertility - post-implantation mortality (e.g. dead and/or
resorbed implants per total number of implants)
REFERENCE :
FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E.
First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year:
4,977,1984
** MUTATION DATA **
TYPE OF TEST : Mutation in microorganisms
TEST SYSTEM : Bacteria - Salmonella typhimurium
DOSE/DURATION : 2 mg/plate
REFERENCE :
JAADDB Journal of the American Academy of Dermatology. (C.V. Mosby Co.,
11830 Westline Industrial Dr., St. Louis, MO 63141) 1979-
Volume(issue)/page/year: 6,652,1982
TYPE OF TEST : Sister chromatid exchange
TEST SYSTEM : Human Fibroblast
DOSE/DURATION : 5 mg/L
REFERENCE :
MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE
Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 58,317,1978
*** STATUS IN U.S. ***
EPA GENETOX PROGRAM 1988, Positive/dose response: In vitro SCE-human
*** END OF RECORD ***