Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No information was given concerning the gender of the animals. The description of the conducted methods was not layed out in detail in Salaman 1956, but were only referred to in another publication (Roe 1955).

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
FURTHER TESTS FOR TUMOUR-INITIATING ACTIVITY: N,N-DI-(2-CHLOROETHYL)-P-AMINOPHENYLBUTYRIC ACID (CB1348) AS AN INITIATOR OF SKIN TUMOUR FORMATION IN THE MOUSE
Author:
Salaman, M.H., and Roe, F.J.C.
Year:
1956
Bibliographic source:
Br. J. Cancer 10, 363-378
Reference Type:
publication
Title:
FURTHER STUDIES ON INCOMPLETE CARCINOGENESIS: TRIETHYLENE MELAMINE (T.E.M.), 1,2-BENZANTHRACENE AND ,3-PROPIOLACTONE, AS INITIATORS OF SKIN TUMOUR FORMATION IN THE MOUSE
Author:
Roe, F.J.C, and Salaman, M.H.
Year:
1955
Bibliographic source:
Br. J. Cancer 9, 177-203
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: subacute dermal toxicity
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: Professor F. Bergel (of the Chester Beatty Research Institute) kindly supplied the test substance

Test animals

Species:
mouse
Strain:
other: strain "S"
Sex:
not specified

Administration / exposure

Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Frequency of treatment:
thrice per week, in total 10 applications
Doses / concentrations
Dose / conc.:
2.9 other: g/kg bw/day (nominal)
Remarks:
Doses / Concentrations:
Basis: per animal dose of pure substance diethyl carbonate

No. of animals per sex per dose:
25 animals (no information on sex distribution)
Control animals:
other: yes, 0.17 % croton oil in acetone

Results and discussion

Effect levels

open allclose all
Dose descriptor:
LOAEL
Effect level:
48.3 - 145 other: g/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
mortality
gross pathology
Remarks on result:
other:
Remarks:
Treated animals: of the 25 animals, 2 animals with tumours (papillomas), 2 other animlas died
Dose descriptor:
dose level: control group
Effect level:
0 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
mortality
gross pathology
Remarks on result:
other:
Remarks:
Control group (0.17 % croton oil in acetone): of 20 animals, 3 animals died, no animals with tumours (papillomas)

Target system / organ toxicity

Critical effects observed:
not specified
Lowest effective dose / conc.:
48.3 other: g/kg bw/day (nominal)
System:
other: papillomas, tumours, lethality

Any other information on results incl. tables

2 animals died during the subacute dermal treatment with 2.9 g of the pure test substance diethylcarbonate. Two surviving animals showed tumours at the end of the croton oil treatment. In the corresponding control group (0.17 % croton oil only) all animals survived and no animal beared any tumours (papillomas).

Applicant's summary and conclusion

Conclusions:
Dermal application of the test substance diethylcarbonate to the clipped backs of mice (10 applications in total, thrice a week) resulted in 2 dead animals and 2 further animals with tumours (papillomas) (total of 25 animals). In the control group 17 mice survived, and none had tumours. In the review of BG Chemie (1994) was stated "In another control group which underwent comparable treatment with croton oil, 4/19 mice had papillomas. The results of the study were evaluated as negative by the authors (Salaman and Roe, 1956).". In the opinion of the author of this IUCLID dossier the results on the repeated dose toxicity (dermal) cannot be concluded as absolutely negative as two animals died and two showed tumors. Therefore a toxic effect of the test substance diethyl carbonate cannot be excluded completely. It should also be remarked when evaluating the above mentioned data that therein definitions and distinctions of "papillomas" and "tumours" are not fully clear.