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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Remarks:
combined repeated dose and reproduction / developmental screening
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Referenceopen allclose all

Title:
No information
Author:
Ministry of Health and Welfare, Japan
Year:
1997
Bibliographic source:
Mininstry of Health and Wefare, Japan. Toxicity Testing Reports of Environmental Chemicals 5, 359-385 (1997)
Title:
No information
Author:
OECD
Year:
1999
Bibliographic source:
OECD SIDS for glycidyl methacrylate, December 1999

Materials and methods

Test guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,3-epoxypropyl methacrylate
EC Number:
203-441-9
EC Name:
2,3-epoxypropyl methacrylate
Cas Number:
106-91-2
Molecular formula:
C7H10O3
IUPAC Name:
oxiran-2-ylmethyl methacrylate
Details on test material:
Produced by Japan Oil Ltd, Lot no. 50905Y, purity 99.93%. Kept at cold and closed dark place until use.

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
Age at study initiation was 10 weeks old (males: 382-414 g, females: 245-282 g)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
Duration of test:
Males: 46 days
Females: 40-47 days

Post exposure observation period: 1 day

Duration of exposure:
Males: 45 days
Females: from 14 days before mating to day 3 of lactation
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
10, 30, 100 mg/kg/day
Basis:
nominal in diet
No. of animals per sex per dose:
12
Details on study design:
Statistical analysis: multi-comparison analysis for continuous data and Fisher's exact test for quantal data

Results and discussion

Results of examinations

Details on results:
Male:
At 30 mg/kg: Salivation at day 25 to day 40 of administration in 5 of 12 animals (This symptom disappeared within 10 minutes after the appearance).
Squamous hyperplasia in forestomach (0: 1/12, 10 mg/kg: 1/11, 30 mg/kg: 11/12, 100 mg/kg: 11/11).

At 100 mg/kg: Salivation continuously after 19 days of administration in all animals (This symptom were observed immediately after administration and almost disappeared within 30 minutes).
Increase in absolute and relative kidney and adrenal weights.
Increase in total protein and albumin.
Squamous hyperplasia in forestomach.

Female:
At 100 mg/kg: Cellular infiltration in forestomach (0: 0/12, 10 mg/kg: 2/12, 30 mg/kg: 3/12, 100 mg/kg: 4/12).

Remarks:
Two males died at 10 mg/kg on day 21 of administration and at 100 mg/kg on day 26 of administration, respectively. Although the reason of two males’ death was not clear, authors concluded it might be no chemical-related.
Salivation and increased serum protein in males was not considered as adverse effects.
Histological change observed in forestomach was considered to be due to irritation of this chemical.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
10 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: local adverse effect: squamous hyperplasia in forestomach
Dose descriptor:
NOAEL
Effect level:
30 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: local adverse effect: squamous hyperplasia in forestomach
Dose descriptor:
LOAEL
Effect level:
30 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: local adverse effect: squamous hyperplasia in forestomach
Dose descriptor:
LOAEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: local advers effect: squamous hyperplasia in forestomach
Dose descriptor:
NOAEL
Effect level:
30 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: systemic adverse effect: increase in absolute and relative kidney and adrenal weights; increase in total protein and albumin
Dose descriptor:
LOAEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: systemic adverse effect: increase in absolute and relative kidney and adrenal weights; increase in total protein and albumin

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

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