Methoxyacetic acid

Repeated dose toxicity: inhalation

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

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methoxyacetic acid

EC Number:

210-894-6

EC Name:

Methoxyacetic acid

Cas Number:

625-45-6

Molecular formula:

C3H6O3

IUPAC Name:

2-methoxyacetic acid

Constituent 2

Reference substance name:

2-methoxyacetic acid

IUPAC Name:

2-methoxyacetic acid

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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0 ppm
Basis:
analytical conc.

Doses / concentrations 2

Remarks:

Doses / Concentrations:
22.8 mg/m3 (= 6.1 ppm)
Basis:
analytical conc.

Doses / concentrations 3

Remarks:

Doses / Concentrations:
58.8 mg/m3 (= 15.7 ppm)
Basis:
analytical conc.

Doses / concentrations 4

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.