4-methylanisole

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

4-methylanisole

EC Number:

203-253-7

EC Name:

4-methylanisole

Cas Number:

104-93-8

Molecular formula:

C8H10O

IUPAC Name:

1-methoxy-4-methylbenzene

Details on test material:

- Name of test material (as cited in study report): p-Methylanisol
- Physical state: liquid - colourless-yellowish
- Analytical purity: > 99.5 %
- Lot/batch No.: P 16
- Stability under test conditions: stability was ensured for at least the study period
- Storage condition of test material: at room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Age at study initiation: approx. 8-9 weeks
- Average weight at study initiation: males 272 +/- 9.6 g; females 192 +/- 4.5 g
- Housing: in groups of 5 animals in cages type D III of Becker without bedding
- Diet: KLIBA rat/mouse laboratory diet 24-343-4 10 mm pellets, Klingentalmühle AG, Kaiseraugst, Switzerland, ad libitum during post exposure observation period
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20 - 24 °C
- Humidity: 30 - 70 %
- Air changes per hr: fully air-conditioned rooms
- Photoperiod (hrs dark/hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Exposure system
Whole-body inhalation system : IKA 02 (glass-steel construction ; BASF Aktiengesellschaft, volume ca. 200 l). The animals were kept singly in compartmentalized wire cages, and were exposed in the chamber.

Generation of the inhalation atmosphere
The test substance was dosed unchanged. A vapor air mixture was generated by means of a
- continuous infusion pump UNITA I (B . Braun)
- glass vaporizer with thermostat (BASF)
By means of the continuous infusion pump the test substance was supplied to the heated vaporizer. The vapors that developed were mixed with supply air and passed into the inhalation system.

Exposure
The following air flow/s (supply air) was set:
blast air : 3000 l/h
The supply air was conditioned via a central air-conditioning system. The exposure system was placed in an air-conditioned laboratory. Temperatures in the exposure system were 19-25°C. Deviations from this specification which would have had any adverse effect on the results of the study did not occur. The inhalation atmosphere was offered to the animals for inhalation for 4 hours.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Gas chromatographical method.

Duration of exposure:

4 h

Concentrations:

6.1 mg/l (maximum technically achievable concentration)

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

The test method was based on OECD 403.
Test Animals: male and female rats
Mean concentration of four samples: 6.10 +/- 0.24 mg/l
Control group: historical (air)
Vehicle: air
Air flow: 3000 l/h
Generation of the inhalation atmosphere: via a continuous infusion pump and a heated vaporizer; developed vapors were mixed with supply air; tested was the maximum concentration that could be achieved technically
Observation period: 14 d post-exposure
Observations:
Body weight: checked before the beginning of the test, after 7 days, at the end of the observation period
Clinical findings: recorded several times during exposure and at least once/work day during the observation period.
Mortality: daily
Pathology: gross necropsy

Statistics:

Concentration/effect relationship: Binomial test following Wittig H: Mathematische Statistik 1974, pp. 32-35

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC0

Effect level:

6.1 mg/L air

Exp. duration:

4 h

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 6.1 mg/L air

Exp. duration:

4 h

Mortality:

No mortality occured during the study.

Clinical signs:

other: Clinical signs during exposure: Accelerated respiration was observed within the first hour, then turning into irregular or intermittent respiration. Eyelid closure was also observed shortly after exposure; salivation within 30 minutes, while abdominal po

Body weight:

Slightly change in body weight gain observed in the second week of the observation period in males compared to the historical controls (decreased in males and increase in females)

Gross pathology:

No pathological findings were noted.

Any other information on results incl. tables

Table 1: Mean body weight of the treated animals compared to historical controls

Mean body weight (g)	before the study		after 7 days		after 14 days
	male	female	male	female	male	female
test group	272	192	300	213	310	220
historical (air) control	248	177	285	196	318	211

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Based on these study results the test material has low acute inhalation toxicity.

Executive summary:

No mortality occured to rats, exposed to a 6.1 mg/l vapor-air mixture of the test material for 4 hours under the experimental conditions chosen (tested was the maximum concentration that could be achieved technically). The LC0 was therefore 6.1 mg/l air.