Chloroacetaldehyde

Endpoint summary

Description of key information

Chloroacetaldeyhde is highly toxic via oral, inhalative and dermal route. All acute studies show severe corrosive effects on skin and eyes.
Due to the hazardous properties of a 45% solution and the risk of an exothermic condensation reaction at acidic pH and/or elevated temperature the pure substanceis not isolated for safety reasons. 

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: Comparable to guideline study but using only 10 animal per dose. Deviation: Only 10 females per dose were used. Preliminary tests had proven that there is no sex-related difference.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: SPF-Wistar-rats
- Weight at study initiation: 192-230g
- Fasting period before study: 16 hours
- Housing: synthetic material cage, shavings
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Route of administration:

oral: gavage

Vehicle:

water

Doses:

63, 100, 160, 250, 315, 400, 500, 630 mg/kg

No. of animals per sex per dose:

10 per dose

Control animals:

no

Details on study design:

Deviation: Only 10 females per dose were used. Preliminary trials had proven that there is no sex-related difference visible.
The LD50 calculation was done by probit analysis according to Lindner & Weber.

Duration of observation period following administration: 14 days
Frequency of observations and weighing: food during observation period: ALTROMIN 1324. Food and water ad libitum.

Sex:

female

Dose descriptor:

LD50

Effect level:

133 mg/kg bw

Based on:

test mat.

95% CL:

> 114 - < 154

Mortality:

59 rats died.
The animals died within 48 minutes up to 24 hours p.a.

Clinical signs:

Decreased activity, pilo errection, hump back behaviour, slowed down respiration, partially sluggishness.

Body weight:

no data

Gross pathology:

The macroscopic examination at autopsy of the dead animals showed reddish mucosa of the small intestines, the blood vessels of the stomach and intestines were moderately injected.
The macroscopic examination of the survivors, killed after 14 days, were without visible alternations.

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The product is classified as being moderately toxic.

Executive summary:

From the mortality figures the acute oral toxicity of a 45 % aqueous solution of Monochloracetaldehyde in female rats after 1 (one) dose by gavage was calculated to be 133 mg/kg. The product is therefore classified as being moderately toxic.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

133 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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study under GLP conditions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: SPF-reared rats (Bor:WISW)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals:
35 male and 35 female SPF-reared rats (Bor:WISW) were obtained from Winkelmann, Versuchstierzucht GmbH & Co KG, Borchen, F.R.G. At the beginning of the study the mean body weight of the males was 168 g and that of the females 141 g. They received the Instituted stock diet for rats and unfluoridated bottled tap water ad libitum. The nutrient composition of the diet and the levels of the various contaminants are determined periodically in batches of the stock diet and in samples of drinking water.

Exposure chamber:
Animals were exposed in a horizontally placed glass tube of the Institute’s design. This allows observation of all animals during exposure. The animals were housed individually. Forts at the entry and exit allow sampling of the test atmosphere. The capacity of the chamber is about 0.015 m³. The exposure chamber was ventilated with 1.2 m³ air/hr. Relative humidity and temperature were measured at least once per hour.

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

It is not stated in the report whether vapor, aerosol or a mix of both were obtained.
Due to safety reasons the classification is done asuming vapor inhalation.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The c. of Cl-acetaldehyde in the test atmosphere was determined by vapour phase infrared spectrometry and calibrated in a closed loop system. The exposure c. was calculated as the mean of the recorded concentration during the entire exposure period.

Duration of exposure:

1 h

Remarks on duration:

observation period: 2 weeks

Concentrations:

concentration level between 0.14g and 8.47g test material/m³

No. of animals per sex per dose:

5 / sex / dose

Control animals:

no

Details on study design:

Seven groups of rats, each consisting of 5 males and 5 females, were exposed one single time for a period of 1 hour. Each group was exposed to chloracetaldehyde at one concentration level between 0.14 g and 8.47 g test material/m³ in the atmosphere.
During exposure the animals were housed individually to minimize filtration of the inspired air by the adjacent animal's fur as a result of crowding.
During the exposure the animals were deprived of water and food.
Immediately after the exposure, the survivors were returned to their living cages (5 males or 5 females to a cage) and were held for an observation period of two weeks. The living cages were suspended in an open rack in an animal room. The temperature and relative humidity in the room were controlled at 22 ~ 3°C and 30-70%, respectively.
The rats were inspected for reactions to treatment during the exposure, and once each day during the observation period. They were held under a 12-hour light and 12-hour dark cycle. Body weights were recorded just prior to exposure and at days 1, 2, 4, 7, and 14. At the end of the observation period the rats were killed and examined for gross pathological changes.

Statistics:

Analytical results:
The temperature of the test atmospheres was controlled at 22 +/- 2°C. Relative humidity was between 51-91%.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

>= 650 - <= 780 mg/m³ air

Based on:

test mat.

Exp. duration:

1 h

Mortality:

24 males, 23 females

Clinical signs:

other: Shortly after the start of the 1-hour exposure period the rats were restless. After a while they were sitting mostly in hump-back position rubbing their snouts. They kept their eyes closed. Three to five minutes after start of the exposure the rats showe

Body weight:

Some males and females showed decreased body weights the first days after exposure, which is a normal observation in this type of experiment.
Most of the survivors gained weight in a normal way, although two animals lost weight considerably.

Gross pathology:

The animals which died during the exposure or during the first two days of the observation period showed oedema in the lungs, sometimes accompanied by atelectasis and in most cases accompanied by a hydrothorax. Frequently the stomachs of these rats were observed to be filled with air, and to a lesser extent also the intestine was filled with air. Sometimes a thrombus in the heart area was found. In some animals of the three lowest concentration groups which were killed at the end of the observation period oedema was observed in the lungs.

Interpretation of results:

Category 1 based on GHS criteria

Remarks:

Migrated information

Conclusions:

From the mortality figures found in this acute inhalation toxicity study it was estimated that an exposure of male and female rats during 1 hour to a test atmosphere containing chloracetaldehyde resulted in a LC50 value between 0.65 and 0.78 g/m³. As a result of the steep concentration-effect curve and natural variability between groups it was not possible to give an exact LC50 value with 95% confidence intervals. According to the decrease in weight in some animals of the lower concentration groups during the observation period which probably would have resulted into death, the LC50 value was estimated to be close to 0.65 g/m³.
The presence of a hydro-thorax could be explained by an induced hypertension. This finding together with oedema and atelectasis in lungs pointed at an impairment of lung functioning. The stomach, caecum as well as intestine observed to be filled with air were caused by mouth breathing.

Executive summary:

The acute inhalation toxicity of chloracetaldehyde was studied by exposing different groups of 5 male and 5 female rats one single time for a period of 1 hour to test atmospheres containing chloracetaldehyde at a concentration between 0.14 and 8.47 g/m³ in air.

From the results of the present study it appeared that the 1h LC50 of chloracetaldehyde for the combined male and female responses was between 0.65 and 0.78 g/m³, the most near to the former value. As a result of the narrow range between these values it was not possible to give a better estimate of the 1-hour LC50 value with 95% confidence limits.

Animals which died shortly after exposure showed signs of oedema and atelectasis in the lungs after autopsy, in most cases accompanied by a hydro-thorax which could be explained by an induced hypertension. These findings together with oedema and atelectasis in lungs were signs of an impairment of lung functioning. Air in stomach as well as in intestine was due to mouth breathing.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

650 mg/m³

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: Only female rats have been used. Preliminary trials showed that there are no sex-related differences.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

In principle according to OECD 402.
Deviation: Only females were used. Preliminary trials had shown that there is no sex-related difference.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: SPF-Wistar-rats
- Weight at study initiation: 155-197 g
- Fasting period before study: 16 hours
- Housing: synthetic material cages, shavings
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Hairless and intact skin on the back, approx. 30 cm2 treated with the undiluted test substance. Occlusive (aluminium foil fixed with Elastoplast 8 cm from Beiersdorf AG, Hamburg).

Duration of exposure:

24 h

Doses:

50, 100, 160, 200, 1250, 5000 mg/kg KG

No. of animals per sex per dose:

6 female rats per dose

Control animals:

no

Details on study design:

After 24 h the dressing was removed and the test substnace removed with warm water. The animals were examined once daily (not on the weeksend) for 14 days. All surving animals were sacrificed after the observation period and subject to macroscopic examination.

Statistics:

The LD50 calculation was done by probit analysis according to Lindner & Weber. Results: LD50

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 140 mg/kg bw

Based on:

test mat.

Mortality:

LD50 = 140 mg/kg body weight. Mortality occured within 60 minutes up to 7 days p.a..

Clinical signs:

Symptoms:
Crying, restlessness, restless behaviour followed
by decreased activity, closed eyes, tremor, ataxia, gasping
dispneua, general bad health condition.
The treated skin areas showed erythema, swelling, yellow discoloration,
indurcisment, necrosis.

Body weight:

no data

Gross pathology:

The macroscopic examination at autopsy of the dead animals
showed heavy erythema and oedema of the subcutis as well as
reddish discoloration of the mucosa of stomach and intestines.
Stomach and intestines were partially filled with red up to
black content.
The macroscopic examination of the survivors, killed after
14 days, did not show visible alternations.

Other findings:

none

Interpretation of results:

Category 2 based on GHS criteria

Remarks:

Migrated information

Conclusions:

LD50 = 140 mg/kg body weight. Mortality occured within 60 minutes up to 7 days p.a.

Executive summary:

From the mortality figures the acute dermal toxicity of a 45 % aqueous solution of Monochloracetaldehyde in female rats was calculated to be 140 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

140 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
Comparable to guideline study.

Justification for selection of acute toxicity – inhalation endpoint
Comparable to guideline study, 1 h exposure.

Justification for selection of acute toxicity – dermal endpoint
Comparable to guideline study.

Justification for classification or non-classification

Classification (OECD-GHS):

acute oral toxicity category 3

acute inhalation toxicity category 1

acute dermal toxicity category 2