Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
other information
Study period:
1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-compliant study performed according to OECD Guideline 412.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
GLP compliance:
yes (incl. certificate)
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material: Methoxyacetic acid
- Analytical purity: 98.2 %
- Molecular weight: 90.09 g/mol
- Physical state: liquid
- Stability under test conditions: 6 months (room temperature)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
28 days
Frequency of treatment:
6 hours/day, 5 days per week
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 ppm
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
22.8 mg/m3 (= 6.1 ppm)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
58.8 mg/m3 (= 15.7 ppm)
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
156.9 mg/m3 (= 42.0 ppm)
Basis:
analytical conc.
No. of animals per sex per dose:
15 males (5 plus 10 for reproduction) and 5 females (plus 20 females for testing of reprotoxicity wihout exposition, mating 2:1)
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:
NOEL
Effect level:
60 mg/m³ air
Sex:
male/female
Basis for effect level:
other: Observed findings.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Species- and strain-specific changes as well as minor changes of clinical parameters were observed. With respect to males, in the high-dose group reduced weight of the thymus (significant) and testes (non-significant) were observed. In the case of females, in the high-dose group a (non-significant) reduced weight of the thymus was observed. Histologic pathology revealed substance-related changes in the testes. No other compound related effects were demonstrated by histopathology. Concerning reproductive effects, investigations on reproduction were inconclusive with respect to male fertility. A NOEL of 60 mg/m³ air was derived.

Applicant's summary and conclusion

Executive summary:

In a subchronic inhalation toxicity study Methoxyacetic acid (98.2% a.i.) was administered to male and female Wistar rats (5/sex/concentration) by nose only exposure at concentrations of 0, 22.8, 58.8, 156.9 mg/m3 for 6 hours per day, 5 days/week for a total of 28 days. In addition, 10 male were exposed as satellite group per dose to investigate reproductive effects. In general, exposition was well-tolerated by animals. No animal died. Species- and strain-specific changes as well as minor changes of clinical parameters were observed. With respect to males, in the high-dose group reduced weight of the thymus (significant) and testes (non-significant) were observed. In the case of females, in the high-dose group a (non-significant) reduced weight of the thymus was observed. Histologic pathology revealed substance-related changes in the testes. No other compound related effects were demonstrated by histopathology. Concerning reproductive effects, investigations on reproduction were inconclusive with respect to male fertility. The NOAEL is 60 mg/m3based on the findings of the study. This subchronic toxicity study in the rat is acceptable and satisfies the guideline requirement (OECD 412) for a subchronic inhalation study in the rat.