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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report date:
1980

Materials and methods

Principles of method if other than guideline:
A study was conducted to determine the toxicity of the test substance to Sprague-Dawley rats exposed by inhalation for 6 h. A group of 5 male and 5 female rats were exposed (whole body) to the test substance at a nominal concentration of 3500 ppm (i.e. 16891.62 mg/m3, or 17.8 mg/L) and were then observed for 14 d.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
4-methylstyrene
EC Number:
210-762-8
EC Name:
4-methylstyrene
Cas Number:
622-97-9
Molecular formula:
C9H10
IUPAC Name:
1-methyl-4-vinylbenzene
Test material form:
liquid
Details on test material:
- Name as cited in report: MCTR-88-79
- Batch/lot no.: RM-07-02-79

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Charles River, Wilmington, USA
- Weight at study initiation: Males, 241-258 g; Females, 210-230 g

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
A single 4 h inhalation exposure was performed.
The test substance vapour was generated using a heated-flask flash evaporator. A fluid metering pump was used to draw the test substance from a 250 mL flask containing approximately 75 mL of test substance. The test substance was pumped through a coil of 1/8” teflon tubing which was immersed in a water bath (50-85°C). The heated test substance was then delivered to the flash evaporator through teflon tubing. Dry air, at a flow rate of 15 L/minute, was passed through a coil of 1/4 copper tubing which was immersed in a water bath (90-96°C). The dry air was heated to 30°C through the coil and was delivered to the flash evaporator. The test substance was vaporised by allowing the heated dry air to pass over the tip of the teflon tubing containing the heated test substance. The vaporisation occurred in a 1 L Erlenmeyer flask heated to approximately 65°C using a heating mantle. The test atmosphere was directed, undiluted, into a 26.5 L glass exposure chamber housing the animals. Chamber temperature range was 25-28°C during the 4 h exposure.
The generation flask, connecting tubing, stopper, and clamp were weighed before and after the exposure. The difference in weight represented the total amount of test substance delivered into the chamber; this, divided by the total volume of air delivered yielded the nominal exposure concentration.
Nominal test material concentration:
During the exposure, a total of 61.85 g of test substance was delivered in a total volume of 3,600 L of air, yielding a nominal exposure concentration of 17.18 mg/L, equivalent to approximately 3500 ppm (mol.wt. 118; 1 mg/L = 207 ppm).
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
3500 ppm (nominal)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing:
Clinical signs: 15 min intervals during the first hour of exposure, then hourly for the remainder of the exposure; on removal of the animals from the chamber; hourly for 4 h post-exposure; and daily thereafter for 14 d.
Body weights: Day 0 (prior to exposure) and on Days 1, 2, 4, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: on Day 14, all animals were killed by exsanguination under ethyl ether anaesthesia and a macroscopic examination was performed at necropsy.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 16 891 mg/m³ air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
There were no mortalities.
Clinical signs:
other: During exposure, all animals showed respiratory abnormalities and increased ocular, nasal, and oral secretions, commencing after 15 minutes. After removal from the chamber, neuromuscular abnormalities were also noted, including weakness, loss of reflex ac
Body weight:
Small transient weight losses were noted in all animals; body weights recovered by day 7 for most animals.
Gross pathology:
There were no remarkable macroscopic findings at necropsy.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the study conditions, ocular, nasal and oral irritation was noted during exposure, decreasing 4 h post-exposure. Neuromuscular impairment was noted after exposure, increasing in severity 4 h post-exposure. All clinical signs had abated by Day 3. Small transient weight losses were noted for all animals. Macroscopic findings at necropsy were unremarkable. The 4 h LC50 was therefore >3500 ppm (i.e. 16891.62 mg/m3, or 17.8 mg/L).
Executive summary:

A study was conducted to determine the toxicity of the test substance to Sprague-Dawley rats exposed by inhalation for 6 h. A group of 5 male and 5 female rats were exposed (whole body) to the test substance at a nominal concentration of 3500 ppm (i.e. 16891.62 mg/m3, or 17.8 mg/L) and were then observed for 14 d. Mortality and clinical signs were recorded frequently during and immediately after exposure and daily thereafter. Body weights were determined on Day 0 (prior to exposure) and on Days 1, 2, 4, 7 and 14. At necropsy, a macroscopic examination was performed on all animals. Under the study conditions, ocular, nasal and oral irritation was noted during exposure, decreasing 4 h post-exposure. Neuromuscular impairment was noted after exposure, increasing in severity 4 h post-exposure. All clinical signs had abated by Day 3. Small transient weight losses were noted for all animals. Macroscopic findings at necropsy were unremarkable. The 4 h LC50 was therefore >3500 ppm (i.e. 16891.62 mg/m3 or 17.8 mg/L) (Norvell, 1980).