Allyl acetoacetate

Toxicity to reproduction

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

Reference

Reference 1

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 2

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 3

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

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

Test material information

Constituent 1

Reference substance name:

Methyl acetoacetate

EC Number:

203-299-8

EC Name:

Methyl acetoacetate

Cas Number:

105-45-3

Molecular formula:

C5H8O3

IUPAC Name:

Methyl acetoacetate

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.