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Toxicological information

Acute Toxicity: inhalation

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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:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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
Observations:
Body weight: weekly (before the beginning, day 7, day 14)
Clinical findings: at least once/work day
Mortality: daily
Pathology: gross necropsy
Statistics:
Concentration/effect relationship: Binomial test following Wittig H: Mathematische Statistik 1974, pp. 32-35

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC0
Effect level:
6.1 mg/L air
Exp. duration:
4 h
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 (mainly within the first hour, then turning into irregular or intermittent respiration) and eyelid closure directly after the beginning of the exposure; salivation, abdominal position, squatting pos
Body weight:
The body weight gain was retarded in the second week of the observation period in comparison to the historical controls.
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