Arsine

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:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute inhalation toxicity study was carried out in male and female rats by whole body inhalation exposure to arsine gas at different concentrations for 4 hours. Post exposure, the animals were observed for 14 days before scheduled necropsy on Day 15 of the study. During necropsy major organs in the thoracic and abdominal cavities were examined for macroscopic abnormalities.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed concentration procedure

Test material

Test material information

Constituent 1

Reference substance name:

Arsine

EC Number:

232-066-3

EC Name:

Arsine

Cas Number:

7784-42-1

Molecular formula:

AsH3

IUPAC Name:

arsane

Test material form:

gas under pressure: liquefied gas

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Charles River CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

During the exposure & post-exposure period, the rats were caged individually and identified by Monel metal ear tags. During both the quarantine and post-exposure periods the cages were were housed in temperature and humidity controlled rooms with a 12-hour photoperiod. Purina-certified pelleted rodent chow number 5002 and tap water were provided ad libitum except during actual exposure .

Administration / exposure

Route of administration:

inhalation: gas

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

The animals were exposed to the test substance atmospheres for 4 hours in a 160 L glass and stainless steel chamber located in a walk-in hood. The chamber supply air consisted of the in-house temperature and humidity-controlled air. The flow rate was 168-190 L/min. The chamber exhaust
was discharged directly into the hood air duct.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

Actual exposure concentrations were determined by atomic absorption analysis of the samples collected on 600 mg two-stage charcoal tubas connected in line with a sampling rotameter and pump.

Duration of exposure:

480 min

Concentrations:

Actual mean exposure concentrations were determined to be as follows: 0, 24, 27, 36, 46, 56 and 110 ppm

No. of animals per sex per dose:

10

Control animals:

yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

143.6 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Any other information on results incl. tables

Deaths generally occurred within 3 days following 30-minute exposure to arsine. There was slightly greater mortality in females than males. Adverse effects noted during exposure included dyspnea, while effects noted post-exposure included a concentration-related increase in hematuria, dark material around the head or the anogenital area, and pallor of ears, eyes, and feet. The higher concentrations resulted in weight loss immediately following exposure, suppressed weight gain during the first week and compensatory weight gains during the second week post-exposure. Necropsy on animals that died showed red, yellow or orange fluid in the bladder, stomach, or intestine, and discoloration of the kidneys, lungs, and liver.

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

The 4-hour inhalation LC50 of arsine in rats was determined to be 45 ppm (equivalent to 143.6 mg/m3).

Executive summary:

An acute inhalation toxicity study was carried out in Sprague Dawley rats according to a scientifically accepted method in compliance with GLP. The study was conducted in two phases. In the first phase, 10 male and 10 female rats were exposed to 75 ppm of arsine for 4 hours. When mortality was observed, the second phase of the study was carried out for the determination of the LC50. Six groups of rats (10/sex) were exposed to arsine gas at concentrations of 0, 24, 27, 36, 46, 56 and 110 ppm for 4 hours. Post exposure, the rats were observed daily for mortality and clinical signs for 14 days. On Day 15 of the study, necropsy was carried out on surviving rats and the major organs of the thoracic/abdominal cavities were examined for macroscopic abnormalities. Deaths generally occurred within 3 days following 30-minute exposure to arsine. There was slightly greater mortality in females than males. Adverse effects noted during exposure included dyspnea, while effects noted post-exposure included a concentration-related increase in hematuria, dark material around the head or the anogenital area, and pallor of ears, eyes, and feet. The higher concentrations resulted in weight loss immediately following exposure, suppressed weight gain during the first week and compensatory weight gains during the second week post-exposure. Under the study conditions, the 4 hour acute inhalation LC50s was determined to be 45 ppm (equivalent to 143.6 mg/m3) with a 95% confidence limit of 42 to 49 ppm (IRDC, 1985).