Registration Dossier

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Referenceopen allclose all

Reference Type:
other: Authoritative data base
Title:
GCID: 15906
Author:
AcTOR Database
Year:
2011
Bibliographic source:
ACToR (Aggregated Computational Toxicology Resource):- EPA/Office of Pollution Prevention and Toxics; (HPV)Challenge Programs Robust Summaries and Test Plans. Available from: http://www.epa.gov/chemrtk/viewsrch.htm on Methyl acetoacetate as of Nov,2,2004
Reference Type:
other: Authoritative data base
Title:
HSDB Number: 1083
Year:
2011
Bibliographic source:
HSDB (Hazardous Substances Data Bank); US national Library of Medicine reviewed by SRC:- EPA/Office of Pollution Prevention and Toxics; High Production Volume (HPV) Challenge Program's Robust Summaries and Test Plans. Methyl Acetoacetate.
Reference Type:
other: Database
Title:
Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test of Methyl acetoacetate by Oral Administratio in Rats
Author:
Hiroyuki Izumi,Eisuke Kimura, Kuninori Yuki¡¤ Tomoko Chijiwa, Emiko Kuwasaki, Tsutomu Ichiki
Year:
2011
Bibliographic source:
Japan Existing Chemical Data Base (JECDB); Safety Assessment Laboratory, Panapharm Laboratories Co., Ltd. 1285 Kurisaki-machi, Uto-shi, Kumamoto; Japan

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
Principles of method if other than guideline:
Data is from ACToR and HSDB database.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 99.40%

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
other: Not applicable
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Males were treated for 7 weeks; females were treated from 14-days prior to mating through day-3 of lactation.
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
100, 300, and 1000 mg/kg/day
Basis:
no data
No. of animals per sex per dose:
Males, 12; females, 12

Results and discussion

Results: P0 (first parental generation)

Details on results (P0)

Paternal/maternal toxic responses by dose: There were no treatment related effects noted in estrous cycle, number of corpora lutea and implantations, copulation or fertility indices for males or females.

Effect levels (P0)

Dose descriptor:
NOEL
Effect level:
> 1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: see 'Remark'
Remarks on result:
other: not specified

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

Details on results (F1)

Fetal toxic responses by dose: There were no treatment related effects noted on gestational days, litter and live born numbers, gestation index, stillborn index, birth index, sex ratio, body weights of offspring at birth and at day 4 post birth, or viability index on day 4. No external abnormalities were observed.

Results: F2 generation

Effect levels (F2)

Remarks on result:
not measured/tested

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
The NOEL of methyl acetoacetate is considered to be more than 1000 mg/kg/day for reproductive performance of parents in rat (male/female).
Executive summary:

Methyl acetoacetate was studied for reproductive toxicity by oral route in Crj:CD(SD) rats with doses of 0, 100, 300 and 1000 mg/kg. There were no premature deaths during the study.No clinical signs observed were considered to be as a result of treatment with the test substance. There were no notable intergroup body weight, food or water consumption differences in either sex. There were no effects noted in hemotology or clinical chemistries considered to be toxicologically significant in either sex. There were no intergroup differences in either organ weights, necropsy or histological findings that were considered to be treatment related in either sex. In terms of reproductive/developmental toxicity, there were no effects related to the test article on reproductive performance of parents and development of the next generation. There were no treatment related effects noted in estrous cycle, number of corpora lutea and implantations, copulation or fertility indices for males or females.There were no treatment related effects noted on gestational days, litter and live born numbers, gestation index, stillborn index, birth index, sex ratio, body weights of offspring at birth and at day 4 post birth, or viability index on day 4. No external abnormalities were observed. The NOEL is considered to be more than 1000 mg/kg/day for reproductive performance of parents and for development of offspring.Thus,the chemical would not induce reproductive toxicity.