Chloroform

Endpoint summary

Description of key information

No OECD guidelines studies on the irritating potential to the skin and eyes have been found. However, the available old studies give evidence that chloroform is an irritant to skin and eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

other:

Version / remarks:

Dermal application following Draize's method; interpretation of results and scoring following official scoring method for cosmetics.

Principles of method if other than guideline:

Dermal application following Draize's method; interpretation of results and scoring following official scoring method for cosmetics.

GLP compliance:

no

Remarks:

did not exist at the time

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Female rabbits weighing between 2.4 and 3.0 kg

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

no

Amount / concentration applied:

no data

Duration of treatment / exposure:

no data

Observation period:

no data

Number of animals:

six

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: no data

Score:

5.6

Reversibility:

no data

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: no scores per time point available

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: no scores per time point available

Irritant / corrosive response data:

Macroscopic observations included moderate to severe erythema and oedema with some superficial peripheral necrosis.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

It can be concluded that chloroform is irritating to the rabbit's skin.

Executive summary:

The skin irritation potential of chloroform was tested in female New Zealand rabbits according to the principles of the Draize test. A single application of pure chloroform resulted in moderate to severe erythema and moderate to severe oedema. The primary dermal irritation index of chloroform was 5.6. Chloroform was classified as a severe skin irritant.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

according to Draize's test and interpretation according to Kay and Calandra

GLP compliance:

no

Remarks:

did not exist at the time

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

female animals weighing between 2.4 and 3.0 kg

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

no data

Duration of treatment / exposure:

no data

Observation period (in vivo):

at least two to three weeks

Number of animals or in vitro replicates:

six

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: no data

Score:

41

Reversibility:

not fully reversible within: 3 weeks

Remarks on result:

other: one rabbit had ocular lesions after 3 weeks

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: no scores per time point available

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: no scores per time point available

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: no scores per time point available

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

other: no scores per time point available

Irritant / corrosive response data:

Severe irritation and lesions of the conjunctivae with occurrence of purulent corneal discharge; mydriasis; developing, aggravating keratitis with apparition of translucent zones in the cornea in 4/6 rabbits, with pannus noted in two animals and hypopyon noted in one animal; recovery from these ocular effects took 2 to 3 weeks for most animals, except for one animal which still had corneal opacity after 3 weeks

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Executive summary:

An eye irritation test with chloroform was performed according to Draize's method with six female New Zealand rabbits. Instillation of pure, liquid chloroform led to severe irritation and lesions of the conjunctivae with occurrence of purulent corneal discharge. Other effects included corneal inflammation. Recovery from these ocular effects took 2 to 3 weeks for most animals, except for one animal which still had corneal opacity after 3 weeks. According to the scoring system of Kay and Calandra, chloroform was considered to be highly irritating to the rabbit's eye.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The skin irritation potential of chloroform was tested in female New Zealand rabbits and the skin reaction was evaluated according to Draize’s method (Duprat et al. 1976). A single application of pure chloroform (duration and extent of occlusion were not documented) resulted in moderate to severe erythema and moderate to severe oedema. The primary dermal irritation index of chloroform was 5.6 on a scale ranging from 0 to 8. Chloroform was classified as a severe skin irritant in the test. No corrosive effects of chloroform to the rabbit skin were mentioned in the study. Another skin irritation test was carried out with chloroform in which the substance was either applied frequently to the uncovered ear of three rabbits or a cotton pad soaked with chloroform was applied to the shaved skin of three rabbits for 24 hours (Torkelson et al. 1976). The prolonged dermal application of the soaked pads resulted in slight hyperaemia with moderate necrosis and a resulting eschar formation. Healing appeared to be delayed on these sites.

The available data give sufficient evidence that chloroform should be considered as being irritating to the skin. In contrast, no evidence of corrosivity of chloroform to the skin was found.

Eye irritation

An eye irritation test with chloroform was performed and an evaluation of the effects was done according to Draize's method with six female New Zealand rabbits (Duprat et al. 1976). Instillation of pure, liquid chloroform led to severe irritation and lesions of the conjunctivae with occurrence of purulent corneal discharge. Other effects included corneal inflammation. Recovery from these ocular effects took 2 to 3 weeks for most animals, except for one animal which still had corneal opacity after 3 weeks (Duprat et al. 1976). Liquid chloroform was instilled into the eye of three rabbits, with and without washing of the eye after treatment. Chloroform was a slight irritant to the conjunctiva, which was reversible after one week. In addition, slight but irreversible corneal injury occurred as evidenced by staining with fluorescein. A purulent exudate occurred for two or more days after treatment (Torkelson et al. 1976). In conclusion, chloroform was found to be irritating to the rabbit's eye. The available studies on the eye irritation potential of chloroform give sufficient evidence that the substance has to be considered as a severe eye irritant. The studies also reported corneal effects that seemed to be not fully reversible after three weeks of observation. However, there is not sufficient evidence of severe damage to the eye induced by exposure to chloroform.

Justification for classification or non-classification

According to Commission Regulation (EU) No 944/2013 of October 2013, amending Annex VI to the Regulation (EC) No 1272/2008 (CLP), chloroform is classified as Category 2 for skin irritation, "H315: Causes skin irritation" and Category 2 for eye irritation, "H319: Causes serious eye irritation".