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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test using close chemical analogue. Study design and performance appear comparable to OECD guideline. Original source reference is not accessible but results are summarised in sufficient detail in secondary sources to allow proper assessment.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Developmental toxicity evaluation of dimethylcarbonate by inhalation in CD-1 mice
Author:
Bevan and Beyer
Year:
1995
Bibliographic source:
International Toxicologist 7(1) 74-P-2
Reference Type:
secondary source
Title:
Office of Environmental Hazard Assessment Final Revised Health Assessment For Dimethyl Carbonate
Author:
Californian Environmental Protection Agency
Year:
2010
Bibliographic source:
OEHHA Assessment, Appendix B (detailed summary of 1995 International Toxicologist paper)
Reference Type:
secondary source
Title:
Non-human toxicity excerpts: peer-reviewed summary of 1995 International Toxicologist paper
Author:
HSDB Database
Year:
2011
Bibliographic source:
US National Library of Medicine Toxicology Data Network

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Mouse inhalation teratology study
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Dimethyl carbonate

Test animals

Species:
mouse
Strain:
CD-1
Details on test animals and environmental conditions:
Mated females

Administration / exposure

Route of administration:
inhalation: vapour
Vehicle:
air
Details on exposure:
Exposure 6h/day for 10 days
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Not specified
Duration of treatment / exposure:
6h/day
Frequency of treatment:
Daily in days 6-15 of gestation (post-mating)
Duration of test:
Parental females terminated on day 18 of gestation
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 ppm
Basis:
other: control group
Remarks:
Doses / Concentrations:
300 ppm
Basis:
other: presumed target concentration (low-dose)
Remarks:
Doses / Concentrations:
1000 ppm
Basis:
other: presumed target concentration (mid-dose)
Remarks:
Doses / Concentrations:
3000 ppm
Basis:
other: presumed target concentration (high-dose)
No. of animals per sex per dose:
96 mated females/dose
Control animals:
yes
Details on study design:
Foetuses from first 30-32 pregnant females/group taken for foetal examinations

Examinations

Maternal examinations:
Bodyweights recorded on days 0, 15 and 18 post-mating; food intakes recorded
Ovaries and uterine content:
Post-implantation losses determined from counts of resorptions
Fetal examinations:
Weights and sexes noted, inspected for abnormalities (external appearance, visceral and skeletal examination)
Statistics:
Statistical significance of any differences between test and control groups was determined
Indices:
Maternal toxicity assessed by bodyweight gain and food intake. Developmental effects assessed by foetal bodyweights and incidence of malformations

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
At 3000 ppm only, bodyweight gains days 0-15 and 0-18 both significantly reduced compared to controls (p<0.01): over days 0-18, bodyweight gain was 27% lower than controls (based on group mean values).
Food intakes significantly reduced at 1000 and 3000 ppm

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
1 000 ppm
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
1 000 ppm
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:yes

Details on embryotoxic / teratogenic effects:
Embryo/foetal toxicity at 3000 ppm: post-implantation losses, altered sex ratio with less surviving males. Foetal bodyweights significantly reduced (both sexes p<0.01) and more foetuses <1g weight.
Teratogenicity at 3000 ppm: cases of fused vertebral arches and skullbone malformations, plus skeletal (sternal and rib bone) variations seen at 3000 ppm only.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Externally visible foetal abnormalities at 3000 ppm (significantly different from controls):

140/277 foetuses in 26/29 litters with cleft palate (p<0.01)

24/277 foetuses in 5/29 litters with small ears (p<0.05)

13/277 foetuses in 5/29 litters with abnormal ear position (p<0.05)

5/277 foetuses in 3/29 litters with unperforated anus (p<0.05)

4/277 foetuses in 2/29 litters with absent or undersized digit(s) (p<0.05).

Skeletal abnormalities at 3000 ppm:

- multiple skullbone malformations

- fused vertebral arches.

Skeletal variation at 3000 ppm:

- sternal bones misshaped

- rib bone shape/size variation.

Applicant's summary and conclusion

Conclusions:
Based on the high exposure concentrations required to cause significant embryo or foetal toxicity and foetal abnormalities, and the close association with maternal toxicity (NOAELs being the same for maternal and developmental toxicity), it is concluded that dimethyl carbonate did not show selective developmental toxicity. It is reasonable to assume that ethyl methyl carbonate would show closely similar activity in this type of study.