Male spermatogenesis seemed to be unaffected: there were no observed changes in the testes (e.g. weight, and macroscopic lesions). At 40 mg/kg bw one female did not mate. Pregnancy rate was 8/10, 9/10, 8/10 and 9/10 at 0, 40, 200 and 100 mg/kg bw, respectively. Duration of gestation, fertility performance and number of live pups were similar for the control and treated groups. Pup mortality, weight, sex and viability did not differ between treatment groups and controls. No effects on reproductive organs and no effects on clinical signs, body weights and macroscopic examination of the pups during their lactation period were observed. The NOAEL for reproductive and developmental effects was ≥1000 mg/kg bw (Beekhuijzen, 2003).
Studies in Humans No data available Conclusion
Based on the outcome of the combined 28-day reproduction/developmental toxicity screening study, the NOAEL for reproductive and developmental effects is ≥1000 mg/kg bw.
Initial Assessment for Human Health
Animal studies on the acute toxicity of DL-lactone by the oral route of exposure are available. The acute oral LD50 was above 2000 mg/kg bw. DL-Lactone is irritating to the skin and the eyes in humans. No sensitisation potential is found in the guinea-pig maximisation test.
In a combined repeated dose reproduction/developmental toxicity screening study (OECD 422) female rats showed aggression and restlessness during part of the study period. In absence of other findings, the NOAEL for repeated dose toxicity was set at 200 mg/kg bw/day.
DL-Lactone does not induce gene mutations in vitro. The in vivo micronucleus test was negative.
In an OECD TG 422 repeated dose reproduction/developmental toxicity screening study with rats exposed to DL-lactone, no effects on reproductive performance, stage of spermatogenesis, pup mortality, weight, sex and viability were reported up to oral doses of 1000 mg/kg bw/day. Animals were dosed prior to and during mating, gestation and following gestation until lactation day 4. Based on the available data, DL-lactone does not show evidence of reproductive or developmental toxicity. The NOAEL for reproductive toxicity is ≥1000 mg/kg bw/day.
HAZARDS TO THE ENVIRONMENT
Acute toxicity tests on three trophic levels are available. All available tests are summarised in table 3.
Acute Toxicity Test Results
DL-Lactone was tested in a semi-static limit test in carps (96 hours exposure). At a measured concentration of 140 mg/L no mortality or other visible effects were observed. Therefore it was concluded that the LC50 for DL-lactone is >140 mg/L (Bogers, 1999a). No immobilised daphnids were observed after 48 hours exposure to a mean measured concentration of 130 mg/L in a semi- static limit test. The EC50 is >130 mg/L (Migchielsen, 1999). In a static test in algae (Selenastrum capricornutum) with DL-lactone no effects on algal biomass and growth rate were observed at the concentration tested (100 mg/L nominal). During the 72-hours test period the measured