Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Study period:
Sep to Oct 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well reported GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): ZK 10882
- Batch No.: 21502111, 21502112

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: physiological saline + 0.085% Myrj 53 in bidest. water
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
34, 174, 1000 mg/kg in an application volume of 10 ml/kg
Basis:
actual ingested
No. of animals per sex per dose:
6
except 34 mg/kg group: 7 males and 5 females
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effects observed up to the highest dose

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

No animal died due to compound administration. One male rat (34 mg/kg group) died because of application failure and one female (34 mg/kg group) died because of arteriopuncture in blood sampling.

Up to and including the highest dose group no compound-related clinical signs, effects on water consumption, ophthalmoscopy, hematology, bone marrow, urinalysis, blood coagulation, organ weights or in gross and histopathology were observed.

From a dose of 174 mg/kg onwards, a slight but not significant increase in serum glucose was observed on day 24 in both sexes, but more pronounced in male rats. Additionally, after a dose of 1000 mg/kg, a slight but not significant decrease in food consumption and body weight gain was observed in the male rats. However, these effects were probably related to the slightly increased serum glucose level, which may have caused a decrease in appetite and which may indicate a reduced metabolic availability of glucose in the body. However, as all vaIues remained within the minimum-maximum range of reference data, all observed effects are regarded to be of no biological relevance.

Applicant's summary and conclusion

Executive summary:

6 -Chlor-Chlormethyldien (ZK 10882) was administered daily via gavage to 7 -6 male and 6-5 female Wistar rats per dose group, in doses of 0, 34, and 1000 mg/kg body weight for a period of 4 weeks. The animals were regularly observed and weighed. Food and water intake was determined. Ophthalmology, hematology and clinical laboratory investigations on blood samples as well as urinalysis and investigations on bone marrow and blood coagulation were performed. Organs and tissues were subjected to gross and histopathological investigations and selected organs were weighed.

Survival was not affected by treatment and no adverse effects were detected up to and including the highest dose group.

Therefore, the NOAEL in male and female rats was established to be 1000 mg/kg body weight/day.