2-methoxy-1-methylethyl acetate

Repeated dose toxicity: oral

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

Test material information

Constituent 1

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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
100 mg/kg/day
Basis:
nominal in water

Doses / concentrations 2

Remarks:

Doses / Concentrations:
300 mg/kg/day
Basis:
nominal in water

Doses / concentrations 3

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.