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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
Study period:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted in compliance with OECD GLP (1992) regulations.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Principles of method if other than guideline:
Deviations: Relative humidity of the room was 50-90%. N-hexane was used rather than dichloromethane to absorb the exposure atmosphere after finding incomplete absorption with dichloromethane. As a result, exposure of animals in group one with dichloromethane use were not reported. Only the results of the exposure of Group 2 utilizing n-hexane are contained in the report.
GLP compliance:
yes
Test type:
fixed concentration procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): T-6329
- Substance type: Mono-constituent
- Physical state: Liquid
- Analytical purity: >93%
- Purity test date: No data
- Lot/batch No.: L12596
- Expiration date of the lot/batch: June 1996
- Storage condition of test material: At room temperature, protected from light

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd
- Age at study initiation: Males: 7 weeks, Females: 11 weeks
- Weight at study initiation: Males: 181.4-194.7 g, Females: 185.0-198.2 g
- Fasting period before study: None
- Housing: Group housed by sex in Makrolon typ IV cages with standard softwood bedding
- Diet (e.g. ad libitum): Kilba 343 rat maintenance diet Batch number 89/95 ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: Six days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 C
- Humidity (%): 50-90%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 21 July 1995 To:10 August 1995

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Nose-only, flow-past exposure using the Sachsse et al. (1973, 1976) method.
- Method of holding animals in test chamber: Restraint tubes
- Source and rate of air: Clean compressed air was utilized at a generator airflow of 10 L/min and a dilution airflow rate of 6 L/min
- Method of conditioning air:
- System of generating particulates/aerosols: Test article vapor was generated using a nebulizer. The vapor was diluted with filtered compressed air to achieve the required exposure concentrations. The generated vapor was passed through a HEPA capsule filter to remove any aerosol droplets present.
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: Temp: 22.6-23.0 C, Humidity: 8.1-11.7 % relative humidity

TEST ATMOSPHERE
- Brief description of analytical method used: Gas chromatography
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
21.69 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were made once per hour during exposure and daily thereafter. Body weights were recorded on Days 1, 4, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 21.69 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
Two male and two female animals were found dead on test days 4 and 5.
Clinical signs:
other: During exposure, no clinical signs were detected in any animals. On test day 4, the following clinical signs were observed: tachypnea in 1 male and 1 female; frightened behavior in 1 male and tremor in 1 male. On test day 5, two of the affected animals
Body weight:
All surviving animals, with the exception of 1 male and 1 female, gained weight consistently during the observation period. A single male and single female lost weight during the first week following exposure, but gained weight to exceed their pre-exposure weight during the second week following exposure.
Gross pathology:
No macroscopic findings were noted in the animals that survived through the observation period. In the animals that died during the observation period the following was observed: lungs incompletely collapsed, dark red discoloration (2/2). The female that died had signs of cannibalism with the larynx, tongue and thyroid gland missing.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, the 4-hour rat inhalation LC50 of the test article is greater than 21.69 mg/L, vapor.
Executive summary:

To evaluate the acute inhalation toxicity of the test article (liquid, purity >93%, molecular weight 300 g/mol, vapor pressure 235 mmHg at 25 C,Batch No. L12596), the test material was administered to Wistar rats for a single continuous 4-hour period. The study was performed under OECD GLP (1992) conditions. The study method was based on OECD Guideline 403 (1981) and EC Directive 92/69/EEC, Part B.2 (1992).  Rats (5/sex) were exposed by nose-only to 21.69 +/- 1.084 mg/L (vapor) MTDID 948, dissolved in n-hexane, for 4 hours. Following exposure, the animals were observed for 14 days. After the observation period, the animals were anesthetized by i.p. injection of sodium pentobarbital (at least 320 mg/kg-bw) and were euthanized by exsanguination. Body weights and clinical observations were recorded. Gross necropsies were performed. During the exposure period, no clinical signs were detected in any animals. One male and one female were found dead on test day 4. On test day 4, the following clinical signs were observed in the surviving animals: tachypnea (1 male/3 females), hunched posture (0/1), ruffled fur (2/1) frightened behavior (1/0), and tremor (1/0). On test day 5, one male and one female were found dead. The remaining animals had returned to normal on test day 5. No clinical signs were detected in the remainder of the observation period. All surviving animals gained weight consistently during the observation period, with the exception of one male and one female, which lost weight during the first week post exposure but regained weight to exceed their pre-exposure weight during the second week post exposure. Macroscopic findings were only detected in the animals that died during the observation period. The findings were: lungs incompletely collapsed, dark red discoloration (2 males/2 females); cannibalism, larynx, tongue, and thyroid gland, missing (0 males/1 female). Based on the results of this study, the 4-hour rat inhalation LC50 of the test article is greater than 21.69 mg/L (vapor).