Registration Dossier

Administrative data

Endpoint:
sub-chronic toxicity: other route
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Description of the method often not very clear. The experimental results are doubtful, because the mortality rate in the control group was rather high.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Skin Initiating Action and Lung Carcinogenesis by Derivatives of Urethane (Ethyl Carbamate) and Related Compounds
Author:
Berenblum, I. et al.
Year:
1959
Bibliographic source:
Biochemical Pharmacology 2, 168-176
Reference Type:
review article or handbook
Title:
No information
Author:
BG Chemie
Year:
1994
Bibliographic source:
Toxicological Evaluations 7: Potential Health Hazards of Existing Chemicals, 7.7 Carcinogenicity, p.40, 1994, BG Chemie, Springer Verlag, ISBN 3-540-57300-3

Materials and methods

Principles of method if other than guideline:
Method: other: subchronic intraperiteoneal injection
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name of the test substance as stated in the publication: diethyl carbonate;
Purchased from Eastman Kodak, Rochester, USA

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male/female

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: saline
Duration of treatment / exposure:
40 weeks
Frequency of treatment:
twice per week
Doses / concentrations
Remarks:
Doses / Concentrations:
11.4 mg, nominal in saline
No. of animals per sex per dose:
30 (total, no information on sex distribution)
Control animals:
other: yes, croton oil

Results and discussion

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

After 20 weeks of treatment 4/30 animals showed skin tumours. The corresponding control group showed in 3 cases of the 45 surviving animals skin tumours (total number of control animals 46).

At the end of the experiment (40 weeks) 12/30 animals showed skin tumours. Analysis of the lungs showed no corresponding carcinogenesis. In the control group 11/40 animals had skin tumours and 2/42 had lung tumours.

Applicant's summary and conclusion

Conclusions:
The test substance diethylcarbonate was intraperitoneally injected in Swiss mice (male/female) for 40 weeks. 40 % of the treated animals showed skin tumours. No treated animal beared any lung tumours.

In a review of the BG Chemie the publication of Berenblum et al. 1959 was also discussed and the author mentioned that this study is "unsuitable for use in evaluation of the possible carcinogenic potential of carbonic acid diethyl ester" because of the small numbers of animals involved and the sometimes low survival rate.