Registration Dossier

Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
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 Diäthylcarbonate; [english translation: Investigations on the toxicity of diethyl carbonate]
Author:
Bornmann, G., and Loeser, A.
Year:
1966
Bibliographic source:
ARCH TOXICOL 22, 98

Materials and methods

Principles of method if other than guideline:
Method: other: multigeneration toxicity study
GLP compliance:
no

Test material

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

Test animals

Species:
rat
Strain:
other: Wistar II BR 46

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Doses / concentrations
Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
>= 214.3 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: other
Remarks on result:
other: -

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:
LOAEL
Effect level:
35.7 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: weight of organs, F3 generation
Remarks on result:
other: -

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

In summary it is stated in the publication that the administration of the test substance in every treatment group (I-III) and every generation (F1 -F3) did not affect the fetal development nor the development of the newborns compared to the control.

In an additional experiment male and female animals from the F1 -generation of the lowest treatment group and control group (10 weeks old, average weight 230 g) were used to measure the respiration of oxygen. In both groups no differences were observed (respiratory quotient 0.82 for both groups).

In 20 weeks old F3 -animals of the two highest treatment groups (0.075, 0.3 % (w/v)) and the control group analysis of the blood sugar was conducted. The obtained values did not differ between the treatment groups and the control.

In the publication it is summarised that the histological analysis of treatment animals and control animals including weights of endocrine organs did not show any differences between treated and control animals for the generation F1 -F3.

However, for the F3 generation it is in addition referred to a table where organ weights are listed upon treatment.

There is no info about the statistical significance of this table data. This data is also not further discussed. Abnormalities in shape etc. have apparentyl not occurred.

Overview of organ weights for F3 generation:

Dose group Sex Number of animals Pituitary average weight (mg) Pituitary average weight (mg/100 g bw) Thyroid average weight (mg) Thyroid average weight (mg/100 g bw) Adrenal gland average weight (mg) Adrenal gland average weight (mg/100 g bw) Ovaries average weight (mg) Ovaries average weight (mg/100 g bw)
Control m 10 11.3 2.4 20.9 4.5 49.2 10.4 / /
0.075 % m 10 11.1 2.3 20.5 4.3 37.8 7.9 / /
0.3 % m 10 11.3 2.4 21.2 4.5 42.8 9.0 / /
Control f 10 11.8 4.0 14.7 4.9 64.3 21.7 77.1 26.1
0.075 % f 10 12.1 4.2 16.7 5.8 56.7 19.5 72.3 25.0
0.3 % f 10 11.4 3.8 18.1 6.0 53.0 17.6 61.8 20.5
Control m+f 20 11.6 3.2 17.8 4.7 56.8 16.1 / /
0.075 % m+f 20 11.6 3.2 18.6 5.0 47.3 13.7 / /
0.3 % m+f 20 11.4 3.1 19.7 5.2 47.9 13.3 / /

For the author of the IUCLID dossier, it may be disputable if there was some effect of the substance on weight development for the following organs (boldly marked numbers): thyroid, adrenal gland, ovaries.

Applicant's summary and conclusion

Conclusions:
In this study rats administered the test substance diethyl carbonate via drinking-water (0.015, 0.075, 0.3 % (w/v)) were mated and the resulting offsprings treated as their parents. In total three generations were bred like this and all offsprings received the corresponding parental concentration of the test substance. The authors of the publication summarised that they never found any differences in fetal development, development of the newborns, blood sugar composition, oxygen respiration and histopathological analysis, including weights of endocrine organs, in the treated groups and the control. The authors of the publication concluded that the test substance diethyl carbonate had no embryotoxic or teratogenic effects. They also pointed out that it may, however, not possible to fully exclude the possibility of teratogenicity.

For the author of the IUCLID dossier, it may be disputable if there was some effect of the substance on weight development of the following organs (boldly marked numbers in the table, in results section): thyroid, adrenal gland, ovaries. These data on the F3 generation were presented in a table of the publication but was not further discussed in respect of their significance.

Data conclusive but not sufficient for classification.