Dimethylcyclopropane-1,1-dicarboxylate

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Adequacy of study:

other information

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: EC B.7

GLP compliance:

yes

Limit test:

no

Test animals

Species:

other: rat / Wistar, HSD, Win: WU

Administration / exposure

Route of administration:

oral: unspecified

Details on oral exposure:

Method of administration:
gavage

Duration of treatment / exposure:

Test duration: 28 days

Frequency of treatment:

Dosing regime: 7 days/week

No. of animals per sex per dose:

Male: 5 animals at 0 mg/kg bw/day
Male: 5 animals at 42 mg/kg bw/day
Male: 5 animals at 126 mg/kg bw/day
Male: 5 animals at 1000 mg/kg bw/day
Female: 5 animals at 0 mg/kg bw/day
Female: 5 animals at 42 mg/kg bw/day
Female: 5 animals at 126 mg/kg bw/day
Female: 5 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
Clinical Observations: Transitory clinical signs in 2 high
dose males were observed. These were slight alopecia in one
male and a decreased activity of two day duration in
another. No clinical signs were observed in high dose
females. Two intermediate dose females revealed a slight
alopecia. Prior to death, the intermediate dose male
revealed several clinical signs such as abnormal gait and
lethargy. None of the clinical signs observed could
reasonably be attributed to the test substance administered.

Body weight: No treatment-related effects were detected.

Food Consumption: No treatment-related effects were
detected.

Water Consumption: No overt intergroup differences were
detected.

Blood Chemistry: High dose animals revealed a statistically
significant decrease of blood urea nitrogen.

Other statistical findings such as an increase of serum
inorganic phosphorus in high dose males, decreased chloride
in high dose females and an increase of serum sodium in low
dose females were considered to be of no toxicological sig-
nificance. In intermediate dose animals and low dose males,
no treatment-related effects were detected.

Laboratory findings:
Hematology: Statistically significant increases in
hematocrit in high and low dose females were observed.
Additionally, statistically significant decrease in
segmented neutrophiles and an increase in lymphocytes in
high dose females were seen.

Urine analysis: High and intermediate dose females revealed
a statistically significant decreased urine pH. Whereas in
the high dose group this was considered to be treatment-
related because of concommitand clinico-chemical and
necropsy findings, there was no further support to the
evidence of a treatment-related effect in the intermediate
dose females.

Necropsy: No macroscopic lesions considered to be related to
treatment with CDM were observed.

Effects in organs:
Histopathology:

Organ weights: High dose females revealed a statistically
significant increase in kidney weight, both absolute and
relative. Low dose females showed a statistically
significant increase in absolute kidney weight.

No microscopic lesions considered to be related to treatment
with CDM were observed in high dose animals compared to the
animals of the control group.

Effect levels

Dose descriptor:

NOAEL

Effect level:

126 mg/kg bw/day (nominal)

Basis for effect level:

other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Classified as: Not classified