4-methylstyrene

Acute Toxicity: inhalation

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:

Two groups of 5 male and 5 female rats were exposed (whole body) to the test substance at nominal concentrations of 3300 or 2280 ppm. Mean analysed chamber concentrations were 1960 and 1510 ppm, respectively (equivalent to ca. 7287.53 and 9459.3 mg/m3, respectively). After exposure, the animals were observed for 14 d.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Vinyltoluene

EC Number:

246-562-2

EC Name:

Vinyltoluene

Cas Number:

25013-15-4

Molecular formula:

C9H10

IUPAC Name:

Ethenylmethylbenzene

Test material form:

liquid

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:
Group 1: Males, 235-294 g; Females, 217-236 g
Group 2: Males, 244-294 g; Females, 238-258 g
- Fasting period before study: Not specified
- Acclimation period: 2-3 weeks

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Two 6 h inhalation exposures were performed. In each exposure, the test substance was placed in a 1 L nipple bottom bubbler and suspended in awaterbath maintained at 72°C. Nitrogen, at flow rates of 20 and 13 L/minute for Groups 1 and 2, respectively, was passed through a 13 m coil of copper tubing (also immersed in the waterbath) and into the bubbler to create a vapour. The vapour-laden airstream then passed through a kjeldahl trap and through a 1 L round-bottomed trap flask before entering a 760 L glass and stainless steel exposure chamber housing the test animals.

Oxygen was pumped into the chamber at 4 L/minute to maintain the oxygen content of the chamber air at ca 20%. The chamber flow was 125 L/minute.

Additional test substance was delivered into the nipple bottom bubbler from a 1L Erlenmeyer reservoir flask when needed using a pump. A similar pump was used to drain test substance from the 1 L trap flask and deliver it into the Erlenmeyer reservoir flask.

The test substance, 1 L nipple bottom bubbler, three necked round-bottom flask, and Erlenmeyer reservoir flask, clamps, tubing, and stoppers were weighed before and after each exposure period. The difference in weight represented the amount of test substance delivered during each exposure.

The nominal concentration of the test substance was calculated by dividing the amount of substance delivered by the total air flow through the chamber during each exposure period.

Chamber air concentration was monitored continuously during each exposure using an ambient air analyser and recorded once each hour. Waterbath temperature, nitrogen flow rate, oxygen flow rate, and chamber air flow were also recorded hourly.

Nominal and analysed test substance concentrations:

Group 1: During the exposure, a total of 728.98 g of test substance was delivered in a total volume of 45,000 L of air, yielding a nominal exposure concentration of 16.2 mg/L or 3,300 ppm (mol.wt. 118; 1 mg/L = 207 ppm). Mean analysed chamber concentration was 1,960 ppm (range 1840 - 2055 ppm; n=6).

Group 2: During the exposure, a total of 505.20 g of test substance was delivered in a total volume of 45,000 L of air, yielding a nominal exposure concentration of 11.2 mg/L or 2,280 ppm. Mean analysed chamber concentration was 1,510 ppm (range 1480 - 1570 ppm; n=6).

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

6 h

Concentrations:

Group 1 (high dose): 3300 ppm (nominal); 1960 ppm (mean analysed)
Group 2 (low dose): 2280 ppm (nominal); 1510 ppm (mean analysed)

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 2 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: any animals dying prematurely were subject to necropsy and macroscopic examination as soon as possible after death. On day 14, all surviving animals were killed (ethyl ether) and a macroscopic examination was performed at necropsy.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1 510 ppm

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other: i.e. >9459.3 mg/m3 air

Mortality:

Group 1 (high dose): One male died on day 1.
Group 2 (low dose): There were no mortalities.

Clinical signs:

other: Group 1 (high dose): During exposure, all animals showed excessive lachrymation, reduced activity and closed eyes. Excessive salivation and laboured breathing were observed frequently. Other signs mainly included gasping, ataxia, rapid breathing, shallow

Body weight:

Group 1 (high dose): Small transient weight losses were noted in all animals; body weights recovered by day 7 for most animals.
Group 2 (low dose): Small transient weight losses were noted in all animals; body weights recovered by day 7 for males, and by day 7/14 in females.

Gross pathology:

Groups 1 and 2: 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 and nasal irritation and neuromuscular impairment were noted after exposure to both concentrations, but these signs abated within 2 d of exposure at the high concentration, and within one day at the low concentration. One rat exposed to the high concentration died on Day 1. Slight, but transient body weight losses were noted for both sexes at each concentration. Macroscopic findings at necropsy were unremarkable for both groups. The 6 h LC50 was therefore >1510 ppm (i.e. >9459.3 mg/m3 or 9.5 mg/L).

Executive summary:

A study was conducted to determine the acute inhalation toxicity of the test substance in Sprague-Dawley rats. Two groups of 5 male and 5 female rats were exposed (whole body) for 6 h at nominal concentrations of 3300 or 2280 ppm. Mean analysed chamber concentrations were 1960 and 1510 ppm, respectively (equivalent to ca. 7287.53 and 9459.3 mg/m3, respectively). After exposure, the animals were 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 and nasal irritation and neuromuscular impairment were noted after exposure to both concentrations, but these signs abated within 2 d of exposure at the high concentration, and within one day at the low concentration. One rat exposed to the high concentration died on Day 1. Slight, but transient body weight losses were noted for both sexes at each concentration. Macroscopic findings at necropsy were unremarkable for both groups. The 6 h LC50 was therefore >1510 ppm (i.e. >9459.3 mg/m3 or 9.5 mg/L) (Norvell, 1980).