1,1,1-trichloroethane

Endpoint summary

Description of key information

The volatile nature of 1,1,1-trichloroethane means that dermal exposure is likely to be limited, unless occluded.  In humans, the potential for dermal irritation is associated with the duration of exposure and irritancy is unlikely following accidental spillage on to the skin, providing the test substance is removed immediately.   In vitro results suggest that if skin contact is maintained there is the potential for cellular damage and this is confirmed in animal studies.
An OECD 404 study in rabbits found 1,1,1-trichloroethane to be irritating, but other studies suggest that the dermal reaction is mild.
Ocular irritation is slight when tested in the rabbit.  Reports from humans exposed to 1,1,1-trichloroethane also confirm mild ocular irritation.

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

The volatile nature of 1,1,1-trichloroethane means that dermal exposure is unlikely to be prolonged unless it is occluded.  A review of the literature suggests dermal exposure to 1,1,1-trichloroethane causes either no effects or reversible effects in humans.  Volunteers who immersed their thumbs in beakers of undiluted 1,1,1-trichloroethane for 30 minutes reported mild burning pain after .10 minutes of exposure (Stewart  1964). Following exposure, mild erythema and fine scaling were visible on the thumb; there was no increase in severity after 30 minutes and the observations were reversible within one hour.   Repeated application to the exposed forearm (Wahlberg 1984), daily for 10 days, produced no visible signs of reaction and no measurable thickening of the skin.  However, an in vitro test for skin irritancy (OECD 431), using both the direct method and the patch method on reconsititued human skin,  found 1,1,1-trichloroethane to be irritant.  Following 4 hours exposure cell viability was reduced, IL-1α release was increased and histology showed notable necrosis (Tornier 2006).  In humans, the potential for dermal irritation is associated with the duration of exposure and irritancy is unlikely following accidental spillage on to the skin, providing the test substance is removed immediately.   In vitro results suggest that if skin contact is maintained there is the potential for cellular damage..

Assessments of the skin irritancy of 1,1,1-trichloroethane in animals reveal slight to moderate reactions.  In the majority of the animals studies contact of 1,1,1-trichloroethane with the skin in maintained by artificial means.  A robust study conducted at TNO (1990), following the OECD 404 guideline, found 1,1,1-trichloroethane to be irritating to the rabbit following 4 hours semi-occlusive exposure; signs of severe erythema and oedema were fully reversible.  Based on single-application studies in rabbits, 1,1,1-trichloroethane was ranked as a moderate skin irritant by Duprat et al. (1976). Torkelson et al. (1958), however, reported only slight reddening and scaliness of rabbits' skin following a single application. Irritation observed following repeated application of the compound for 10 days was only slightly more noticeable and quickly disappeared after the end of treatment (Torkelson et al. 1958).  Kronevi et al. (1981) studied cellular changes produced in the intact skin of guinea pigs by exposure to 1 mL of undiluted 1,1,1-trichloroethane under a cover glass for durations ranging from 15 minutes to 16 hours. Prolonged exposure for several hours caused severe inflammatory reactions in the upper part of the dermis, the extent of which increased with exposure.

Although extended dermal contact with relatively concentrated 1,1,1-trichloroethane may cause irritation and burning sensations of the skin of humans, most evidence in humans and animals indicates that this compound is not a strong skin irritant, unless exposure is prolonged.

An eye irritation study in the rabbit, instilling 0.1 mL of 1,1,1-trichloroethane, and scoring according toe Kay and Calandra, found the substance to be only slightly irritating (Duprat 1976).  Similar results were observed by Torkelson (1958).  Humans briefly exposed to high 1,1,1-trichloroethane vapour concentrations reported only mild eye irritation (ATSDR 2006)

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

GHS

Based on the available animal data, the TNO study, which follows the OECD 431 guidelines for skin irritation, 1,1,1 -trichloroethane was found to be skin irritant as mean scores of 4 were observed in the test. Therefore a classification of skin irritant category 2 is supported.

Moreover 1,1,1-trichloroethane was found to be slightly irritating to eye and therefore falls under class 2B Mild Irritant.