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Diss Factsheets

Administrative data

Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data

Data source

Reference
Reference Type:
publication
Title:
Physicians' Desk Reference. 50th Ed. Montvale, NJ: Medical Economics Co. p.2349-50 (1996)
Year:
1996
Bibliographic source:
Physicians' Desk Reference. 50th Ed. Montvale, NJ: Medical Economics Co. p.2349-50 (1996)

Materials and methods

Test guideline
Qualifier:
no guideline available
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
1-Piperidinecarboxylic acid, 4-(8-chloro-5,6-dihydro-11H-benzo(5,6)cyclohepta(1,2-b)pyridin-11-ylidene)-, ethyl ester
EC Number:
935-907-9
Cas Number:
79794-75-5
Molecular formula:
C22H23ClN2O2
IUPAC Name:
1-Piperidinecarboxylic acid, 4-(8-chloro-5,6-dihydro-11H-benzo(5,6)cyclohepta(1,2-b)pyridin-11-ylidene)-, ethyl ester
Test material form:
solid: particulate/powder

Test animals

Species:
other: Mice and rats
Strain:
not specified
Sex:
male/female

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
18 months study (mice)
24 months study (rats)
Doses / concentrationsopen allclose all
Dose / conc.:
40 mg/kg bw/day
Remarks:
mice
Dose / conc.:
25 mg/kg bw/day
Remarks:
rats

Results and discussion

Results of examinations

Histopathological findings: neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Male mice given 40 mg/kg had a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) than concurrent controls.
In rats, a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in males given 10 mg/kg and males and females given 25 mg/kg.

Target system / organ toxicity

Critical effects observed:
yes
System:
hepatobiliary
Organ:
liver
Treatment related:
yes
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
In an 18 month oncogenicity study in mice and a 2 year study in rats, loratadine was administered in the diet at doses up to 40 mg/kg (mice) and 25 mg/kg (rats). In the carcinogenicity studies, pharmacokinetic assessments were carried out to determine animal exposure to the drug. AUC data demonstrated that the exposure of mice given 40 mg/kg of loratadine was 3.6 (loratadine) and 18 (active metabolite) times higher than a human given 10 mg/kg. Exposure of rats given 25 mg/kg of loratadine was 28 (loratadine) and 67 (active metabolite) times higher than a human given 10 mg/day. Male mice given 40 mg/kg had a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) than concurrent controls. In rats, a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in males given 10 mg/kg and males and females given 25 mg/kg.