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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)
Rationale for reliability incl. deficiencies:
other: study performed according to OECD and GLP guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

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)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
4-methyloxazole-5-carbonitrile
EC Number:
213-709-7
EC Name:
4-methyloxazole-5-carbonitrile
Cas Number:
1003-52-7
Molecular formula:
C5H4N2O
IUPAC Name:
4-methyl-1,3-oxazole-5-carbonitrile

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
Males were exposed for 29 days, i.e. 2 weeks prior to mating, during mating, and up to termination. Females were exposed for 40, 41, 44 or 54 days, i.e. during 2 weeks prior to mating, during mating, during post-coitum, and during at least 4 days of lactation
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:

Basis:

No. of animals per sex per dose:
10 per sex per dose
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Key result
Dose descriptor:
NOAEL
Effect level:
>= 40 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical signs
food consumption and compound intake
mortality
organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

-

Applicant's summary and conclusion

Conclusions:
Based on these results, a parental, reproduction and developmental No Observed Adverse Effect Level
(NOAEL) of 40 mg/kg was determined.
Executive summary:

A combined 28-day repeated dose toxicity study with the reproductionldevelopmental toxicity screen was conducted in compliance with OECD 422 (1996), OECD 421 (1 995), and OECD 407 (2008) as well as in compliance with GLP. The test substance CMO was administered to four groups of ten male and ten femate Wistar (Han) rats by oral gavage to the test substance at 0 (vehicle), 1, 8 and 40 mg/kg.

The following parameters were evaluated: clinical signs, functional observations, locomotor activity, body weights, food consumption, reproductionldevelopmental parameters, observations pups, clinical pathology (haematology, clotting potential, clinical biochemistry), stage of estrous cycle (on day of planned necropsy), macroscopy, Organ weights, and histopathology. In addition, blood samples were analyzed for exposure control on the last day of treatment. Chemical analyses of forrnulations were conducted during the study to assess accuracy, homogeneity and stability.

Analysis of plasrna samples taken on the last day of treatment at the peak period of occurrence of clinical signs (2 hours after dosing) showed that animals were dose-dependently exposed to CMO. No parental toxicity was observed at any dose level. No toxicologically significant changes were noted in any of the parental parameters investigated in this study (i.e. ctinical appearance, functional observations, body weight, food consumption, clinical laboratory investigations, stage of estrous cycle, Organ weights, macroscopic examination, and microscopic examination).

No reproduction/developmental toxicity was observed at any dose level.