Hexachloroacetone

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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

Principles of method if other than guideline:

Adult, male 1 albino rats of the Wistar strain, averaging 150 g in weight were used for these studies. They were housed 5 to a cage at a room
temperature of 23 +/- 1 °C. The animals were fasted overnight (water ad libitum but no food) prior to dosing by stomach tube. Ten rats were dosed at each of 4 or 5 dosages of a compound, After dosing, the rats were fed a commercial chow ad libitum. They were kept under observation for 4
weeks following treatment and any death occurring within that time were included in calculation of the result.
The LD50 values were calculated by the minimum approximate chi-square normit method of Berkson (1955).

GLP compliance:

not specified

Test type:

other: min. 4 doses tested

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

Adult, male, albino rats of the Wistar strain, averaging 150 g in weight, were used for these studies. They were housed 5 to a cage at a room temperature of 23 +/- 1 °C. The animals were fasted overnight (water ad libitum but no food) prior to dosing by stomach tube. Ten rats were dosed at each of 4 or 5 dosages of a compound. After dosing, the rats were fed a commercial chow ad libitum. They were kept under observation for 4 weeks
following treatment and any deaths occurring within that time were included in calculation of the result.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The animals were fasted overnight (water ad libitum but no food) prior to dosing by stomach tube. Ten rats were dosed at each of 4 or 5 dosages of a compound, After dosing, the rats were fed a commercial chow ad libitum. They were kept under observation for 4
weeks following treatment and any death occurring within that time were included in calculation of the result.

Doses:

only the result is included in the publication, no data about doses

No. of animals per sex per dose:

10 male animals per dose

Control animals:

not specified

Details on study design:

The animals were fasted overnight (water ad libitum but no food) prior to dosing by stomach tube. Ten rats were dosed at each of 4 or 5 dosages of a compound, After dosing, the rats were fed a commercial chow ad libitum. They were kept under observation for 4
weeks following treatment and any death occurring within that time were included in calculation of the result.

Statistics:

The LD50 values were calculated by the minimum approximate chi-square normit method of Berkson (1955).

Sex:

male

Dose descriptor:

LD50

Effect level:

1 370 - 1 730 mg/kg bw

Based on:

test mat.

Mortality:

LD50 = 1550 +/- 180 mg/kg bw (determined with 40-50 rats)

Clinical signs:

other: Moderate to severe central nervous system depression was noted following administration, and this persisted for several days. No other signs were discernible.

Gross pathology:

No abnormalities were evident on gross autopsy.

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Migrated information

Conclusions:

LD50 = 1550 +/- 180 mg/kg bw (determined with 40-50 rats).

Executive summary:

The acute LD50's of several perhalogenated acetones by oral routes are presented. The compounds were administered oraJly to rats. The LD50 of hexachloroacetone after oral administration was found to be 1550 +/- 180 mg/kg bw (determined with 40-50 rats). The compound was administrated orally. hexachloroacetone caused depression of the central nervous system, but, otherwise, no specific toxic signs were associated with lethal doses. Oral administration did not lead to pulmonary damage from any of these compounds.

The mechanism of the lethal action of the latter compounds is not apparent in these studies.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 550 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

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

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

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.

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.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

660 ppm

Based on:

test mat.

Exp. duration:

3 h

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

5 900 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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

Principles of method if other than guideline:

Adult, male, albino rabbits,averaging 2 kg in weight, were used, usually 10 al each of 3 or 4 dosagee of a compound. The hair from the trunk of the
animal was removed by means of an electric dipper. A rubber girdle was fitted, and the rabbit was placed in an individual restraining stock
(Draize et al., 1944) for the 24-hour exposure period. The test liquid was then injected under the girdle and permitted to remain in contact with the
skin for 24 hours. At the end of the contact period, the girdles were removed, the skin was wiped dry, and the rabbits were examined and returned to individual cages. They were maintained under observation at 23 ± 1 °c for 4-6 weeks, during which they were fed a commercial chow.
The LD50 values were calculated by the minimum approximate chi-square normit method of Berkson (1955).

GLP compliance:

not specified

Test type:

other: min. 3 dose groups

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

Adult, male, albino rabbits,averaging 2 kg in weight, were used, usually 10 al each of 3 or 4 dosagee of a compound.
The hair from the trunk of the animal was removed by means of an electric clipper.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The hair from the trunk of the
animal was removed by means of an electric dipper. A rubber girdle was fitted, and the rabbit was placed in an individual restraining stock
(Draize et al., 1944) for the 24-hour exposure period. The test liquid was then injected under the girdle and permitted to remain in contact with
the skin for 24 hours. At the end of the contact period, the girdles were removed, the skin was wiped dry, and the rabbits were examined and
returned to individual cages. They were maintained under observation at 23 ± 1 °c for 4-6 weeks, during which they were fed a commercial chow.

Duration of exposure:

24h

Doses:

no data

No. of animals per sex per dose:

10 at each of 3 or 4 dosages of a compound

Control animals:

not required

Details on study design:

A rubber girdle was fitted, and the rabbit was placed in an individual restraining stock (Draize et al., 1944) for the 24-hour exposure period. The test liquid was then injected under the girdle and permitted to remain in contact with the skin for 24 hours. At the end of the contact period, the girdles
were removed, the skin was wiped dry, and the rabbits were examined and returned to individual cages. They were maintained under observation at 23 ± 1°C for 4 - 6 weeks, during which they were fed a commercial chow.

Statistics:

The LD50 values were calculated by the minimum approximate chi-square normit method of Berkson (1955).

Sex:

male

Dose descriptor:

LD50

Effect level:

1 900 - 4 060 mg/kg bw

Based on:

test mat.

Mortality:

Mild central nervous system depression preceded death, but no other abnormal signs were evident.

Clinical signs:

other: There was no measurable amount of material remaining under the girdle at the end of the exposure period, The exposed area appeared erythematous and was very clearly delineated from the adjacent unexposed areas. These exposed areas then became scaly or de

Gross pathology:

No abnormalities were present on gross autopsy except for tbe discoloration and edema of the exposed skin.

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

LD50 = 2980 +/- 1080 mg/kg bw (determined with 30-40 albino rabbits).

Executive summary:

The acute LD50 of dermal administration is presented. The compound was administrated by dermal application (occlusive, 24 h) to rabbits. The compound caused some depression of the central nervous system, but otherwise, no specific toxic signs were associated with lethal doses. Dermal application did not lead to pulmonary damage from hexachloroaceton.

The mechanism of the lethal action of the latter compounds is not apparent in these studies.

In the latter case, the pulmonary absorption is less than half the gastrointestinal absorption. These calculations are interpreted as evidence that the lethal action of these compounds excluding hexachloroacetone is manifested entirely systemically.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 980 mg/kg bw