Registration Dossier

Administrative data

Endpoint:
additional toxicological information
Type of information:
other: study comparison
Adequacy of study:
supporting study
Study period:
1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Evaluation report only with limited data

Data source

Reference
Reference Type:
other: evaluation report
Title:
Unnamed
Year:
1983
Report Date:
1983

Materials and methods

Type of study / information:
Evaluation of studies with DME performed in two different laboratories
Principles of method if other than guideline:
Developmental toxicity studies (equivalent/similar to OECD 414) had been carried out in two different laboratories. In both labs,
pregnant rats had been exposed to the test substance during day 6 through day 15 of pregnancy (rather than from day 6-19 as is required in the current guideline)
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test compound: dimethylether (DME)
Purity (TNO studies): 99.8%
Purity (Haskell studies) : 99.9%

Results and discussion

Any other information on results incl. tables

From the results obtained in the different studies it was concluded - by the authors of the Haskell report that:

a. the exposure of rats during day 6 through 15 of pregnancy to test atmospheres containing up to 4.0% was demonstrated to have a maternal effect at the 2.0 % level and higher

b. the "no-effect level", demonstrated for the conceptus was 0.125%.

By the authors of the CIVO report that:

a. the exposure of rats during day 6 through 15 of pregnancy to test atmospheres containing up to 2.8% was non-toxic to pregnant females (only a slight reduction in BW gain was noted in females exposed to 2.8% during the exposure-period)

b. the "no-adverse-embryo/foetotoxic effect level" demonstrated for the conceptus was 2.8%.

By both that:

a. embryo/foetotoxicity was evident at the 4.0% level as expressed by decreased foetal body weights and an increased incidence of several skeletal variants

b. the exposure of rats to test atmospheres, containing 0.125, 0.5, 2.0 or 4.0% during day 6 through day 15 of pregnancy did not induce any teratogenic effect in rat foetuses

c. DME was not demonstrated to represent a unique hazard to the rat conceptus.

Applicant's summary and conclusion

Executive summary:

Data from different embryotoxicity/teratogenicity studies with the test substance, carried out at the Haskell Laboratory for Toxicology and Industrial Medicine, Newark, Delaware, U.S.A. and at the Institute CIVO-Toxicology and Nutrition TNO, Zeist, the Netherlands, were studied and mutually compared to evaluate the embryo/foetotoxic or teratogenic potential.

In a pilot and a main study carried out at CIVO, pregnant rats were exposed to atmospheres containing 0 (control), 2.0 or 2.8% DME for 6 hours/day from day 6 through day 15 of pregnancy. In two successive studies carried out at Haskell, pregnant rats were exposed, under the same conditions, to either 0, 0.5, 2.0 of 4.0% in the first study or to 0, 0.125, 0.5 or 2.0% in the second study .

No abnormalities in condition or behaviour were observed in the CIVO studies. The significance of the decreased response to a sound stimulus, observed in the Haskell studies at the 4.0% and 2.0% dose level is not clear. Diminished weight gain during the exposure period was observed in the 4.0% group at Haskell, and a slight body weight gain reduction was observed in the 2.8% group at TNO. Body weights of the remaining test substance groups as well as food consumption figures did not indicate treatment-related effects. Decreased foetal bodyweight was apparent at the 4.0% dose level only.

Visceral examination of foetuses did not reveal any abnormality attributable to the treatment. Skeletal examination revealed an increased incidence of a number of minor skeletal variants in the 4.0% dose group. Although the incidence of one or two minor skeletal variants was slightly increased at the 0.5, 2.0 and 2.8% DME level, those observations were not classified as abnormalities since they were the only effects and these would not likely have any significant effect on the health or function of the individual.

From the results obtained in the different studies it was concluded

- by the authors of the Haskell report that:

a. the exposure of rats during day 6 through 15 of pregnancy to test atmospheres containing up to 4.0% was demonstrated to have a maternal effect at the 2.0 % level and higher

b. the "no-effect level", demonstrated for the conceptus was 0.125%.

- by the authors of the TNO report that:

a. the exposure of rats during day 6 through 15 of pregnancy to test atmospheres containing up to 2.8% was non-toxic to pregnant females (except for a sight reduction in BW gain in females exposed to 2.8% during the exposure period)

b. the "no-adverse-embryo/£oetotoxic effect level" demonstrated for the conceptus was 2.8%.

- by both that:

a. embryo/foetotoxicity was evident at the 4.0% level as expressed by decreased foetal body weights and an increased incidence of several skeletal variants

b. the exposure of rats to test atmospheres, containing 0.125, 0.5, 2.0 or 4.0% during day 6 through day 15 of pregnancy did not induce any teratogenic effect in rat foetuses

c. DME was not demonstrated to represent a unique hazard to the rat conceptus.