Studies in Humans
Single instances of dermal irritation in production workers after prolonged and intensive exposure have been noted; but there are no studies available (R. Strobel and A. Flückiger, 1995).
Eye Irritation Studies in Humans DL lactone may cause irritation upon direct contact in occupational settings (unpublished data). Conclusion
Based on occupational exposure experience in humans DL-lactone is expected to be irritating to the eyes and upon prolonged and intensive exposure also to the skin.
3.1.4 Sensitisation Studies in Animals Skin
In a guinea-pig maximisation test performed according to OECD 406, no sensitising potential of DL-lactone was found. Animals were induced with a 5% solution (intracutaneous) and a 50% solution (epicutaneous in presence of SDS to elicit irritation) and challenged with a 50% solution. The concentrations applied were selected based on the outcome of a preliminary irritation study. No skin reactions were seen after the challenge exposure in both experimental and control animals (Teunissen, 2005b).
Studies in Humans No data available Conclusion
Based on the guinea-pig maximisation test it can be concluded that DL-lactone is not sensitising to the skin.
Repeated Dose Toxicity
For repeated dose toxicity a combined 28-day reproduction/developmental toxicity screening study was available, performed according to OECD 422.
Studies in Animals Oral
Rats (10/sex/treatment) were treated by gavage with 0, 40, 200 and 1000 mg/kg bw DL-lactone during 14 days prior to mating (1:1) and 14 days (males) or maximum 56 days (females) thereafter. Females were allowed to litter and to nurse their pups until day 4 of lactation. No mortality occurred. Females at 1000 mg/kg bw were aggressive and restless during day 5-15 of treatment. There were no treatment related effects on body weight, food consumption, haematology, clinical chemistry, organ weights, macroscopy and histopathology. Based on the behavioural effects in females the NOAEL was set at 200 mg/kg bw (Beekhuijzen, 2003).