chlorcyclizine hydrochloride

Chlorcyclizine hydrochloride is a histamine H1 antagonist.

Signaling Pathways >> GPCR/G Protein >> Histamine Receptor

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Inflammation/Immunology

Histamine H1[1]

Pregnant rats administered 30, 60, and 90mg/kg Chlorcyclizine during the sensitive period for palate development survived until scheduled sacrifice on Gestation Days (GDs) 17 or 21. The rats administered 60 or 90mg/kg Chlorcyclizine have transient adverse clinical signs (chromorhinorrhea, red peri-oral substance, urogenital staining, and scant stool) and a concomitant body weight loss of 7% and 11%, respectively, over the dosing interval. Rats administered 30mg/kg Chlorcyclizine do not exhibit any adverse clinical signs, but do not gain weight over the dose interval as would be expected during pregnancy. Based on the testing facility’s historical control database (16 studies, n=380). pregnant rats typically gain about 6% body weight from GDs 12 to 15[1].

Rats[1] Timed-mated CRL:CD [SD] female rats between 9 and 13 weeks of age at initiation of dosing and weighing between 245 and 363 g are used. Rats are administered a single daily oral gavage dose of 30, 60, or 90 mg/kg Chlorcyclizine (n=8/group) during the sensitive period for palate development, GDs 11 to 14. These doses are selected such that 30 mg/kg is a likely no-effect dose and higher doses of 60 and/or 90 mg/kg will induce a moderate or high incidence of fetal cleft palate. Given that CRL:CDs [SD] rats have an extremely low incidence of spontaneous cleft palate in the testing laboratory, as well as to avoid unnecessary use of animals, a methylcellulose control group is omitted[1].

[1]. Enright BP, et al. Effects of the histamine H1 antagonist Chlorcyclizine on rat fetal palate development. Birth Defects Res B Dev Reprod Toxicol. 2010 Dec;89(6):474-84.

Loratadine | Histamine | Pitolisant hydrochloride | Cimetidine | Osthole | Clemastine fumarate | Ebrotidine | JNJ-7777120 | Famotidine | Cetirizine Dihydrochloride | Desloratadine | Ketotifen fumarate | Lodoxamide | Meclizine dihydrochloride | Chlorpheniramine maleate

MOLECULAR FORMULA :

C18-H21-Cl-N2.Cl-H

MOLECULAR WEIGHT :

337.32

WISWESSER LINE NOTATION :

T6N DNTJ AYR&R DG& D &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CLDND* Compilation of LD50 Values of New Drugs. (J.R. MacDougal, Dept. of National Health and Welfare, Food and Drug Divisions, 35 John St., Ottawa, Ont., Canada)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

300 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CLDND* Compilation of LD50 Values of New Drugs. (J.R. MacDougal, Dept. of National Health and Welfare, Food and Drug Divisions, 35 John St., Ottawa, Ont., Canada)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CLDND* Compilation of LD50 Values of New Drugs. (J.R. MacDougal, Dept. of National Health and Welfare, Food and Drug Divisions, 35 John St., Ottawa, Ont., Canada)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

200 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CLDND* Compilation of LD50 Values of New Drugs. (J.R. MacDougal, Dept. of National Health and Welfare, Food and Drug Divisions, 35 John St., Ottawa, Ont., Canada)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

35 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CLDND* Compilation of LD50 Values of New Drugs. (J.R. MacDougal, Dept. of National Health and Welfare, Food and Drug Divisions, 35 John St., Ottawa, Ont., Canada)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

125 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CLDND* Compilation of LD50 Values of New Drugs. (J.R. MacDougal, Dept. of National Health and Welfare, Food and Drug Divisions, 35 John St., Ottawa, Ont., Canada)

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

75 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

27ZQAG "Psychotropic Drugs and Related Compounds," 2nd ed., Usdin, E., and D.H. Efron, Washington, DC, 1972 Volume(issue)/page/year: -,213,1972

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CLDND* Compilation of LD50 Values of New Drugs. (J.R. MacDougal, Dept. of National Health and Welfare, Food and Drug Divisions, 35 John St., Ottawa, Ont., Canada) ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

840 mg/kg/2W-I

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - other changes Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Metabolism (Intermediary) - lipids including transport

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 65,100,1982 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

240 mg/kg

SEX/DURATION :

female 12-15 day(s) after conception

TOXIC EFFECTS :

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: 18,199,1978

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

100 mg/kg

SEX/DURATION :

female 12-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Specific Developmental Abnormalities - homeostasis

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: 147,391,1965

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

500 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :

TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 8,87,1977

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

3024 mg/kg

SEX/DURATION :

male 28 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands

REFERENCE :

BIREBV Biology of Reproduction. (Soc. for the Study of Reproduction, 309 W. Clark St., Champaign, IL 61820) V.1- 1969- Volume(issue)/page/year: 7,398,1972

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

650 mg/kg

SEX/DURATION :

female 10-22 day(s) after conception

TOXIC EFFECTS :

Reproductive - Maternal Effects - postpartum Reproductive - Effects on Newborn - physical

REFERENCE :

VAAZA2 Virchows Archiv, Abteilung B: Cell Pathology. (Springer-Verlag, Heidelberger Pl. 3, D-1000 Berlin 33, Fed. Rep. Ger.) V.1- 1968- Volume(issue)/page/year: 39,59,1982

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

400 mg/kg

SEX/DURATION :

female 13-16 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 10,839,1972

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

800 mg/kg

SEX/DURATION :

female 11-14 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

AJOGAH American Journal of Obstetrics and Gynecology. (C.V. Mosby Co., 11830 Westline Industrial Dr., St. Louis, MO 63146) V.1- 1920- Volume(issue)/page/year: 95,109,1966

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

200 mg/kg

SEX/DURATION :

female 12-13 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 Reproductive - Specific Developmental Abnormalities - eye/ear

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 194,168,1971

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

200 mg/kg

SEX/DURATION :

female 12-13 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 194,168,1971