OECD SIDS 5. TOXICITY
ID: 79-50-5 DATE: 18.01.2006
non-pregnant. Of the 40 mg/kg bw/d dose group, one female did not mate and two females mated in the second mating period. Of the 200 mg/kg bw/d dose group, two females were non-pregnant. And of the 1000 mg/kg bw/d dose group, one female was non-pregnant. Mating performance, duration of gestation, fertility parameters and number of pups at birth were similar for the control and treated groups.
Breeding data Breeding parameters were unaffected by treatment up to 1000 mg/kg bw/d. The number of dead and living pups at first litter check, postnatal loss between days 0-4 post-partum, living pups at day 4 post-partum and the viability index were similar for control and treated groups. dl-Lactone from Roche Dalry, batch BX226, purity 99.8% as per certificate of analysis. dl-Lactone was administered by daily oral gavage to male and female Wistar rats at dose levels of 40, 200 or 1000 mg/kg bw/d. The males were exposed for 2 weeks prior to mating, during mating and up to termination (28 days for all males). The females were exposed for 2 weeks prior to mating, during mating, during post-coitum and at least 4 days of lactation. The mean duration of treatment of females was 43 days, with a minimum of 28 days and a maximum of 56 days. Parental toxicity was assessed by observing mortality, clinical signs, body weights, food consumption, functional observations, clinical laboratory investigations, macroscopic examination, organ weights and microscopic examination. At 40 mg/kg bw/d, no parental toxicity was observed. At 200 mg/kg
bw/d, no parental toxicity was observed. At 1000 parental toxicity consisted of clinical symptoms and restless behaviour) in females during days 5 treatment and of increased serum potassium level
mg/kg bw/d, (aggressive to 15 of in males.
Reproductive toxicity was assessed by observing the mating performance, fertility indices and number of pups at birth. No reproductive toxicity was observed up to 1000 mg/kg bw/d. Breeding toxicity was assessed by observing the number of postnatal and breeding loss during lactation. No breeding toxicity was observed up to 1000 mg/kg bw/d. Developmental toxicity was assessed by observing clinical signs, body weights and macroscopic examination of the pups during their lactation period. No developmental toxicity was observed up to 1000 mg/kg bw/d. In conclusion, gavage treatment of male and female Wistar rats with dl-Lactone at dose levels of 40, 200 or 1000 mg/kg bw/d for at least 28 days (during premating, mating, post-coitum and lactation) revealed slight parental toxicity in animals receiving 1000 mg/kg bw/d; this toxicity was transient during the study in the case of the females, while the males were killed after 28 days so that potential recovery could not be assessed. Reproductive, breeding and developmental parameters were unaffected up to 1000 mg/kg bw/d. Based on the results in this combined repeated dose toxicity
study with reproduction/developmental screening test, definitive sub-chronic parental NOAEL was established
the as being
200 mg/kg bw/d while the LOAEL
valid without restriction test under GLP.