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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Addendum to the subchronic oral study with rats and dogs
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
secondary source
Title:
Unnamed
Year:
1974

Materials and methods

Principles of method if other than guideline:
Livers from 5 rats/group were obtained at the termination of the 14-day or 3-month segments of the subacute toxicity studies and from 4 dogs/group after treatment for 3 month.
The livers were weighed and liver/body weight (relative liver weight) ratios calculated. p-nitroanisole metabolism was determined according to the procedure employed by Kinoshita et al. 81966), Toxicol Appl. Pharmacol. 9, 505-513 and Hoffman et al. (1968), Toxicol Appl Pharmacol 12, 464-472
GLP compliance:
no
Type of method:
in vivo
Endpoint addressed:
not applicable

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
purity: 96.4%

Test animals

Species:
other: rat and dog
Strain:
other: Harlan + Beagle
Sex:
male/female

Administration / exposure

Route of administration:
other: oral
Vehicle:
other: rat: unchanged dog: 5 % aqueous acacia solution
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
14-days or 3-month
Frequency of treatment:
daily
Post exposure period:
no
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
undilited
Basis:
other: rats
Remarks:
Doses / Concentrations:
0, 5, 20 or 80 mg/kg bw/d in a 5 % aqueous accacia solution
Basis:
nominal conc.
dog
No. of animals per sex per dose:
rat: 20 males and 20 females/dose
dog: 2 males and 2 females/dose
Control animals:
yes, concurrent vehicle

Results and discussion

Details on results:
daily gavage administration of OCT to female rats for 14 days had no statistically significant effect on the rate of hepatic p-nitroanisole O-demethylation to p-nitriphenol. The rate of metabolism was increased significantly in male rats given 80 and 320 mg/kg/day, but at least a part of the difference between these rats and their respective controls was due to an unusually low rate of metabolism in the controls. Administration of OTC for 3 month had no significant effect on the rate of metabolism in either male or female rats.
Oral administration of OCT to dogs for 3 month had no effect on the rate of p-nitroanisole metabolism.

Any other information on results incl. tables

no data

Applicant's summary and conclusion

Executive summary:

Livers from 5 rats/group were obtained at the termination of the 14-day or 3-month segments of the subacute toxicity studies and from 4 dogs/group after treatment for 3 month.

The livers were weighed and liver/body weight (relative liver weight) ratios calculated. p-nitroanisole metabolism was determined.

daily gavage administration of OCT to female rats for 14 days had no statistically significant effect on the rate of hepatic p-nitroanisole O-demethylation to p-nitriphenol. The rate of metabolism was increased significantly in male rats given 80 and 320 mg/kg/day, but at least a part of the difference between these rats and their respective controls was due to an unusually low rate of metabolism in the controls. Administration of OTC for 3 month had no significant effect on the rate of metabolism in either male or female rats.

Oral administration of OCT to dogs for 3 month had no effect on the rate of p-nitroanisole metabolism.