Hexachloroacetone

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:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Acute Toxicity of Some Perhalogenated Acetones

Author:

Joseph F. Borzelleca, David Lester

Year:

1965

Bibliographic source:

TOXICOLOGY AND APPLIED PHARMACOLOGY 7, 592-597 (1965)

Materials and methods

Principles of method if other than guideline:

Adult albino rats, averaging about 150 g in weight, were the test animals. They were exposed in groups of 10, 5 males and 5 females, for periods
of 0.5, 1, 3, or 6 hours. With each compound 50-120 rats were used in a series of exposures to concentrations of vapor which produced
mortalities bracketing the 50% level. Survivors were observed for 15 days following the exposure. The LC50 was estimated by inspection of
a log-log plot of concentration vs. percentage mortality.

GLP compliance:

not specified

Test type:

other: 4 dose groups

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexachloroacetone

EC Number:

204-129-5

EC Name:

Hexachloroacetone

Cas Number:

116-16-5

Molecular formula:

C3Cl6O

IUPAC Name:

hexachloropropan-2-one

Details on test material:

Boiling point: 204 °C
Specific gravity: 1.73 (25°C)

Test animals

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

Adult albino rats, averaging about 150 g in weight, were the test animals. They were exposed in groups of 10, 5 males and 5 females, for periods
of 0.5, 1, 3, or 6 hours. With each compound 50-120 rats were used in a series of exposures to concentrations of vapor which produced
mortalities bracketing the 50% level. Survivors were observed for 15 days following the exposure.

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

The vapor concentrations of the liquid acetones were prepared by the syringe method: the liquid was metered into the air stream by means of a
motor-driven syringe. The bottom of the mixing chamber was heated to ensure prompt vaporization of the liquids. The mixture was led into a
10-liter glass desiccator which served as the exposure chamber.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

> 0.5 - <= 6 h

Remarks on duration:

4 dose groups

Concentrations:

no data

No. of animals per sex per dose:

groups of 10, 5 males and 5 females

Control animals:

not specified

Details on study design:

Adult albino rats, averaging about 150 g in weight, were the test animals. They were exposed in groups of 10, 5 males and 5 females, for periods
of 0.5, 1, 3, or 6 hours. With each compound 50-120 rats were used in a series of exposures to concentrations of vapor which produced
mortalities bracketing the 50% level. Survivors were observed for 15 days following the exposure.
The vapor concentrations of the liquid acetones were prepared by the syringe method: the liquid was metered into the air stream by means of a
motor-driven syringe. The bottom of the mixing chamber was heated to ensure prompt vaporization of the liquids. The mixture was led into a
10-liter glass desiccator which served as the exposure chamber.

Statistics:

The LC50 was estimated by inspection of a log-log plot of concentration vs. percentage mortality.

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC50

Effect level:

660 ppm

Based on:

test mat.

Exp. duration:

3 h

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

360 ppm

Based on:

test mat.

Exp. duration:

6 h

Mortality:

Most of the fatalities occurred 2-6 days after exposure. No sex difference in response was evident.
The cause of death is not well defined. In the case of hexachloroacetone administered by inhalation the extent of the pulmonary damage and its long persistence suggest that this might be the cause of death. The pulmonary absorption is less than half the gastrointestinal absorption. These
calculations are interpreted as evidence that the lethal action of hexachloroacetone is not manifested entirely systemically.

Clinical signs:

other: When the damage to the lung was slight and seen only microscopically) the lung weight was usually' within the normal range. When lung edema was evident upon gross examination, the lung weight was increased. Liver weights in all cases were within the norm

Body weight:

no data

Gross pathology:

All animals, both survivors and nonsurvivors, were autopsied, and the lungs, liver, heart, and kidneys were examined grossly and microscopically.
The lungs and livers of the rats which were sacrificed were weighed. There were no histopathologic findings in heart, kidney or liver.
When the damage to the lung was slight and seen only microscopically) the lung weight was usually' within the normal range. When lung edema
was evident upon gross examination, the lung weight was increased. Liver weights in all cases were within the normal range. Gross examination of
the lungs immediately after- death presented a picture of widespread hemorrhage. Edema, hemorrhage and congestion of the lungs was evident
microscopically 15 days after termination of exposures to hexachloroacetone, with little indication of repair of the injury.

Any other information on results incl. tables

No sex difference in response was evident. Most of the fatalities occurred 2-6 days after exposure.

Pulmonary edema is a prominent feature of the response to inhalation of hexachloroacetone.

When the damage to the lung was slight and seen only microscopically, the lung weight was usually within the normal range. When lung edema was evident upon gross examination, the lung weight was increased. Liver weights in all cases were within the normal range. Gross examination of the lungs immediately after- death presented a picture of widespread hemorrhage only in the case of hexachloroacetone. Edema, hemorrhage and congestion of the lungs were evident microscopically 15 days after termination of exposures to hexachloroacetone, with little indication of repair of the injury. There were no histopathology findings in heart, kidney or liver.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Migrated information

Conclusions:

LC50 = 660 ppm (3h) and 360 ppm (6 h) bw (determined with 50-120, male/female).

Executive summary:

The acute LD 50 of inhalative administration is presented. The compound was administrated by inhalation to rats. The compound caused some depression of the central nervous system, but, otherwise, no specific toxic signs were associated with lethal doses. Pulmonary edema is a prominent feature of the responsetoinhalation of hexachloroacetone, but only minor or negligible lung-irritant effects were observed from exposure to the other compounds.

The mechanism of the lethal action of the latter compounds is not apparent in these studies. In the case of hexachloroacetone administered by inhalation the extent of the pulmonary damage and its long persistence

suggest that this might be the cause of death. The pulmonary absorption is less than half the gastrointestinal absorption. These

calculations are interpreted as evidence that the lethal action of hexachloroacetone is not manifested entirely systemically.