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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
07.11.1989 to 30.01.1990
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
There were significant restrictions. These restrictions were that no haematology, clinical chemistry, urinalysis or histopathology were conducted.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
To investigate the potential for repeated dose toxicity.
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% suspension of methocel A4M and distilled water
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
Five days per week, for two consecutive weeks
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
25 mg/kg bw/day (actual dose received)
Dose / conc.:
100 mg/kg bw/day (actual dose received)
Dose / conc.:
400 mg/kg bw/day (actual dose received)
Dose / conc.:
1 600 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
8
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Sex:
male/female
Basis for effect level:
other: The biological/toxicological significance of effects observed at the lowest dose (25 mg/kg bw/day) was unclear.
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No overt signs of toxicity or behavioural changes were observed in the animals during the exposure period. Two female animals from the 1600 mg/kg bw/day treatment group died due to dosing error. At terminal sacrifice five animals had lesions consistent with gavage accidents. These five animals had terminal body weights that were slightly to severely below the group means. Two rats had liver lesions that were considered to be spontaneous.

Statistically significant increases in relative liver weight in both males and female animals occurred when the data from the 400 and 1600 mg/kg bw/day treatment groups were compared to controls. Additionally, a statistically significant increase was recorded when the relative liver weights of the females in the 100 mg/kg bw/day was compared to the control values. The absolute liver weight reflected statistically significant increases among those female rats treated with 400 and 1600 mg/kg bw/day. Therefore it is clear that treatment-related liver weight increases were observed at doses of 100 mg/kg bw/day and above. The effects at 25 mg/kg bw/day in both sexes were unclear.

Applicant's summary and conclusion

Conclusions:
In a two-week oral gavage study (DCC, 1990; reliability score 4) a NOAEL could not be determined because the biological/toxicological significance of effects on the liver at the lowest dose was unclear. However, it is the opinion of the current study summary author that the liver effects were adaptive, and that effects on terminal body weight were due to dosing error injuries.