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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
Study period:
1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The test report from the Japanese Ministry of Health & Welfare is not available, but all data have were validated by the Japanese authorities within the OECD-SIDS program and were taken into account in the EU risk assessment report on this substance by France.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998

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)
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-methoxy-1-methylethyl acetate
EC Number:
203-603-9
EC Name:
2-methoxy-1-methylethyl acetate
Cas Number:
108-65-6
Molecular formula:
C6H12O3
IUPAC Name:
2-methoxy-1-methylethyl acetate
Details on test material:
- Name of test material (as cited in study report): Propylene glycol methyl ether acetate
- Analytical purity: >99.9 %

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:
- Age at study initiation:
- Weight at study initiation:
- Fasting period before study:
- Housing:
- Diet (e.g. ad libitum):
- Water (e.g. ad libitum):
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light):


IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Distillled water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Males: for 44 days from 2 weeks prior to mating.
Females: from 14 days before mating to day 3 of lactation (41-45days)
Frequency of treatment:
one administration/day
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
100 mg/kg/day
Basis:
nominal in water
Remarks:
Doses / Concentrations:
300 mg/kg/day
Basis:
nominal in water
Remarks:
Doses / Concentrations:
1000 mg/kg/day
Basis:
nominal in water
Control animals:
yes, concurrent vehicle
Details on study design:
Post-exposure period: none

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Clinical biochemistry findings:
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined

Effect levels

Dose descriptor:
NOAEL
Effect level:
>= 1 000 other: mg/kg
Sex:
male/female
Basis for effect level:
other: No adverse effects observed up to limit dose.

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Based on the results of this study NOAEL for the rats is 1000 mg/kg/day
Executive summary:

Using OECD combined repeat dose and reproductive/developmental toxicity screening test SD rats received gavage propylene glycol methyl ether acetate (purity >99.9%) doses of 0 (Vehicle: distilled water), 100, 300 and 1000 mg/kg/day, for males for 44 days from 2 weeks prior to mating and for females for 41 -45 days from 14 days before mating to day 3 postpartum.

A dose of 1,000 mg/kg/day of PMA exerted some effects in both male and female rats. In males, depressions of body weight gain and a tendency for decrease in food consumption were observed. In females, low body weight gain during the premating period at 1,000 mg/kg was also observed.  Blood examination revealed decreases in glucose and inorganic phosphorus. An increase in relative weight of the adrenals was also noted. In females, body weight gain was lower than in the control during the premating period. Tissue pathology revealed none of the alteration of tissues at the highest dose group for both sexes.

 

The animals were sacrificed on the day 4 of lactation for females. No effects related to chemical exposure were observed maternally at 1,000 mg/kg, although there was a single unsuccessful copulation at this dose level which was not statistically significantly different from the control (p<0.05). Similarly, no effects related to the chemical exposure were observed in foetal data at 1,000 mg/kg. Reproductive toxicity of PGMA in rats by oral administration is not observed at the highest dose.

 

 A NOAEL was thus established at 1,000 mg/kg bw/day for both sexes.

 

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