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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
multi-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable publication with very detailed description of the conducted methods.

Data source

Reference
Reference Type:
publication
Title:
Untersuchungen zur Toxikologie von Diäthylcarbonat; [english translation: Investigations on the toxicity of diethyl carbonate]
Author:
Bornmann, G., Loeser, A.
Year:
1966
Bibliographic source:
ARCH TOXICOL 22, 98

Materials and methods

Principles of method if other than guideline:
chronic oral administration of the test substance with regard to offspring development.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of the test substance as stated in the publication: "Diäthylcarbonat"
Purity: > 99.5 %
Purchased from: "Farbenfabriken Bayer AG, Werk Uerdingen"

Test animals

Species:
rat
Strain:
other: Wistar-Stamm II BR 46
Sex:
male/female

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on mating procedure:
Preliminary mating occurred during 20 days (daily changing of sexual partners) with 10 males and 10 females from two groups (treated with 0.015 % test substance, and control without test substance)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
100 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
0.0 % (w/v), 0.0 mg/kg bw (males, females) -> control group
0.015 % (w/v), 3 mg/day, 6.5 mg/kg bw (males), 10.7 mg/kg bw (females);
0.075 % (w/v), 10 mg/day, 20.7 mg/kg bw (males), 35.7 mg/kg bw (females);
0.3 % (w/v), 60 mg/day, 130 mg/kg bw (males), 214.3 mg/kg bw (females);
Basis:
nominal in water
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

open allclose all
Dose descriptor:
NOAEL
Effect level:
>= 130 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: histopathological examination of reproduction organs and fertility
Remarks on result:
other: Generation not specified (migrated information)
Dose descriptor:
NOAEL
Effect level:
>= 214.3 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: histopathological examination of reproduction organs and fertility
Remarks on result:
other: Generation not specified (migrated information)

Results: F2 generation

Effect levels (F2)

Dose descriptor:
NOAEL
Generation:
other: F3
Effect level:
10.7 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: weights of ovaries were slightly lower in the two higher dosage groups compared to control
Remarks on result:
other:
Remarks:
F3 generation; according to publication, however, no clear treatment-related signs of toxicity or of macroscopic or microscopic effects on the organs

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

The only diseases related to the reproductive system in the parental animals were vulvar cancers in one female of group III (administration of 0.3 % diethylcarbonate) and one female of the control group (possibly also a tumour of the intestine). Ovarian cysts were not taken into account as these are observed frequently in rats and were therefore not regarded as relevant. Fertility was not affected in treatment groups compared to the controls in any generation.

In group III of the F3 -generation the weights of the ovaries were slightly decreased compared to the control group and group II (25.0 mg/100 g bw in group II, 0.075 %; 20.5 mg/100 g bw in group III, 0.3 %; 26.1 mg/100 g bw in control group); 10 females per group.

According to the publication no clear treatment-related signs of toxicity or of macroscopic or microscopic effects on the organs were found in any of the treated groups.

The authors of the publication summarised that there were no indications of diethyl carbonate having an organotropic effect.

Applicant's summary and conclusion

Conclusions:
Rats were administered the test substance diethyl carbonate chronically at concentrations of up to 0.3 % (w/v) in drinking-water and possible effects on the reproduction system analysed. Histopathological analysis of testes and ovaries resulted in vulvar cancers in one treated female and one control female. Ovarian cysts were not taken into account as these would be frequently observed in rats. They were therefore not relevant in the opinion of the authors of the publication.

Another part of the experiment was a fertility-study over 3 generations (parent -> F1 -> F2 -> F3) in which the offsprings were always treated with the corresponding dose of the test substance of their parents. Compared to the controls the fertility of the treated animals was not affected by the test substance as stated in the publication. A lower weight of the ovaries in F3-females was observed in the highest dose group compared to the control group and the next lower treatment group (20.5 mg/100 g bw at 0.3 % versus 25.0 mg/100 g bw at 0.075 % and 26.1 mg/100 g bw in the control group). There was no statement made about the statistical significance of this data nor was it discussed in the results or discussion section. The data was only presented in a table. A concluding statement about the effect of the substance on ovary weight appears therefore not possible for this study. Other effects related to ovaries were not reported. There was no generation F4 bred with generation F3 as parents to investigate further influences on reproduction.

Date conclusive but not sufficient for classification.