Chloroform

Endpoint summary

Description of key information

No valid study on the irritating potential to the skin and eyes has been found. However, the available data give evidence that chloroform is an irritant to skin and eyes. Valid studies on the inhalation toxicity of chloroform demonstrate that an irritation of the respiratory tract is induced by subacute, subchronic or chronic inhalation exposure to the substance at doses above those inducing adverse systemic effects.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

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.

Effects in the nasal passage

Irritation of the respiratory tract induced by chloroform vapours was reported from acute (Méry et al. 1994), sub-acute (Larson et al. 1996), sub-chronic (Templin et al. 1996) and chronic (Yamamoto et al. 2002) inhalation studies. Effects included nasal lesions and cell proliferation in the olfactory epithelium and the nasal passage. Cell proliferation was observed in the nose (ethmoid region) of male F-344 rats following inhalation exposure at 10 mg/m3 for 6 h/day for 4 days, however, at 50 mg/m3 only minimal to mild lesions were seen and the effects were transient (Templin et al. 1996b). A late atrophy was present not only in the areas of early cell proliferation but in the whole ethmoid region of the nasal cavity after 13 weeks of exposure. The atrophy was minimal at exposure levels of 10 mg/m3 and more distinct at higher exposure concentrations. Following exposure to 50 mg/m3 for 6 h/day for 7 consecutive days, male F-344 rats had lesions in nasal turbinates, including increased cell proliferation in central, proximal, and distal regions of the first endoturbinate, and histological changes in the central turbinate bone (Larson et al., 1994a; Méry et al., 1994). Cell proliferation was also seen in the nasal turbinates of female B6C3F1 mice exposed at 10 mg/m3, but not at 1.5 mg/m3, for 6 h/day for four consecutive days (Larson et al., 1996). Increased cell proliferation was detected in the first endoturbinate of the nasal passage in female B6C3F1 mice exposed to 50 mg chloroform/m3, 6 h/day, for 7 consecutive days (Méry et al., 1994) but no microscopic damage was seen in the nasal passages of female B6C3F1 mice exposed to up to 1500 mg/m3 for 6 h/day for 7 consecutive days. Thus, it appears that the notable effects of chloroform on the respiratory tract occur with exposure concentrations of 50 mg/m3.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Effect level: empty Endpoint conclusion: Adverse effect observed

Justification for classification or non-classification

The GHS classification proposed according to the data available is Category 2 for skin irritation, "H315: Causes skin irritation" and is Category 2 for eye irritation, "H320: Causes eye irritation". No classification is proposed for respiratory tract irritation as the nasal effects are covered by the classification proposed for repeated dose toxicity (agreed by the TC C&L on September 2007 during the revision of the classification of chloroform). According to EU directive 67/548/EEC, the substance is classified as skin irritant (R38) and eye irritant (R36).