Hexachlorocyclopentadiene

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Effects of inhalation exposure to hexachlorocyclopentadiene on rats and monkeys

Author:

Rand GM, Nees PO, Calo CJ, Alexander DJ, Clark GC

Year:

1982

Bibliographic source:

Journal of Toxicology and Environmental Health, 9:5-6, 743-760

Report date:

1982

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexachlorocyclopentadiene

EC Number:

201-029-3

EC Name:

Hexachlorocyclopentadiene

Cas Number:

77-47-4

Molecular formula:

C5Cl6

IUPAC Name:

hexachlorocyclopentadiene

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Kent, UK
- Weight at study initiation: 200-300 g
- Fasting period before study: 16 hours before blood sampling
- Housing: before exposure rats were housed in stainless steel cages
- Diet: standard laboratory food (Spratt's Lab Diet no. 1) available at all times except during inhalation exposure, during urine sample collection, and for approx 16 hrs before blood sampling
- Water: tap water available at all times except during inhalation exposure, during urine sample collection, and for approx 16 hrs before blood sampling

ENVIRONMENTAL CONDITIONS
- Temperature: 20-25 °C
- Photoperiod: 12 h light and dark cycle

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: rats were exposed in stainless steel and glass chambers
- Exposure chamber volume: 1 m^3
- Source and rate of air: A diffusion tube was charged with a known amount of Hexachlorocyclopentadiene. Dry, filtered, compressed air flowing across the diffusion tube in an oven picked up the compound vapors and then was directed into the exposure chamber inlet. Generator flow rate was 10 L/min and chamber flow rate was 40 L/min.
- Method of conditioning air: Exposure concentrations were controlled by a combination of oven temperature, flow rate of concentrated Hex vapors, and chamber airflow rate.

TEST ATMOSPHERE
- Brief description of analytical method used: Exposure concentrations were monitored continuously with a total hydrocarbon analyser or by charcoal adsorption with subsequent analysis by flame ionisation detection (FID) GC.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.28 ppm, 1.4 ppm, 2.5 ppm, 3.1 ppm, 3.3 ppm, 3.4 ppm, 4.0 ppm, 5.8 ppm

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighed before and after exposure and signs of toxicity were recorded daily.
- Necropsy of survivors performed: yes
- Other examinations performed: signs of toxicity, body weight

Statistics:

Calculated LC50s and 95% confidence limits were determined by methods of Bliss (1938).

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

1.6 ppm

Based on:

test mat.

95% CL:

0.6

Exp. duration:

4 h

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

3.5 ppm

Based on:

test mat.

95% CL:

2.1

Exp. duration:

4 h

Effect levels 3

Sex:

male

Dose descriptor:

LC50

Effect level:

0.018 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Effect levels 4

Sex:

female

Dose descriptor:

LC50

Effect level:

0.04 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

Mortality data indicated a biphasic toxic response at the intermediate exposure levels. The first phase consisted of the exposure period and the following 48 hours, with most deaths occurring around the first day after exposure. The second phase consisted of postexposure days 7-14, during which period deaths were evenly distributed. Mortality was highest in males.

Clinical signs:

other: At test concentrations of 1.4 ppm and above some degree of sedation was exhibited by all animals, while at the highest dose of 5.8 ppm most animals showed lacrimation, salivation, and ataxia.

Body weight:

Male and female rats in the group exposed to the lowest concentration (0.28 ppm) gained weight throughout the experiment. Rats in all other test groups (1.4 - 5.8 ppm) lost weight over the 14 day observation period.

Gross pathology:

No grossly observable pathological changes in animals exposed to 0.28 ppm. Animals surviving exposure to 1.4 ppm or greater exhibited significant pulmonary abnormalities, characterised by red focal or diffuse consolidation that progressed to severe generalised hemorrhage and hepatization. Severity increased with exposure concentration. Some animals exposed to 5.8 ppm also exhibited rhinorrheas and mottling of the liver.

Any other information on results incl. tables

Table showing acute LC50 mortality data for rats exposed to Hexachlorocyclopentadiene concentrations

Hex concentration (ppm)	Sex	Number of dead rats on postexposure days of LC50
		0	1	2	3	4	5	6	7	8	9	10	11	12	13	14	Total
0.28	m	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	f	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
1.4	m	0	0	0	0	0	0	0	1	0	2	1	0	1	0	1	6
	f	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1
2.5	m	0	0	1	0	0	0	0	1	1	0	2	0	0	0	0	5
	f	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
3.1	m	1	1	1	0	0	0	0	2	1	2	1	0	0	0	1	10
	f	0	0	0	0	1	0	0	0	1	0	0	2	0	2	0	6
3.3	m	0	1	1	0	0	0	0	1	0	2	0	1	0	1	1	8
	f	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	2
3.4	m	0	0	1	0	0	0	0	1	0	0	1	1	1	0	0	5
	f	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
4.0	m	0	3	1	0	0	0	0	0	0	1	1	2	1	0	0	9
	f	0	1	1	1	0	0	0	0	2	0	0	2	1	1	0	9
5.8	m	3	6	0	0	0	0	0	0	0	0	0	0	0	0	0	9
	f	1	2	6	0	0	0	0	0	0	1	0	0	0	0	0	10
Total	m	4	11	5	0	0	0	0	6	2	7	6	4	3	1	3	52
	f	1	3	7	1	1	0	0	0	4	1	0	5	1	5	0	29

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

This acute inhalation toxicity study indicated that male rats are more sensitive than female rats to Hexachlorocyclopentadiene exposure, and observed biphasic mortality. The study found the 4 hour LC50 and 95% confidence limits to be 1.6 ± 0.6 ppm for male rats and 3.5 ± 2.1 for females.

Executive summary:

The acute inhalation toxicity of hexachlorocyclopentadiene to Sprague-Dawley rats was determined using a procedure similar to the OECD Guideline for Testing of Chemicals 403, with acceptable restrictions. The study was non GLP compliant and assessed as having a Klimisch score of 2. Eight groups consisting of 10 male and 10 female rats were exposed to different vapour concentrations of the test substance, and mortality, body weight and signs of toxicity were observed over 14 days. The study found male rats to have greater sensitivity to the test substance than female rats, and determined the 4 hour LC50 and 95% confidence limits to be 1.6 ± 0.6 ppm (males) and 3.5 ± 2.1 (females). This meets the GHS criteria for classification as acute inhalation toxicity hazard Category 1.