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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No other available studies
Effect on fertility: via oral route
Dose descriptor:
NOAEL
73.2 mg/kg bw/day
Additional information

The parental systemic NOAEL for the 2-generation reproduction study in rats (Astroff, 1998) was 100 ppm (equivalent to 6.4/7.3 mg/kg/day [males/females]), based on decreased body weight and body weight gains seen at higher doses. There were no reproductive effects observed, thus the reproductive NOAEL was considered to be the maximum dose tested, 1000 ppm (equivalent to 73.2/84.0 mg/kg/day [males/females). The offspring NOAEL was considered to be 100 ppm (equivalent to 6.4/7.3 mg/kg/day [males/females]) based on decreased pup body weights and overall decreased body weights throughout treatment.


Short description of key information:
7.8.1 Toxicity to reproduction:
KS - 2gen.rat. Astroff, 1998. KL.1, NOAEL reproductive M: 73.2, F: 84 mg/kg/day; Offspring M: 6.4, F: 7.3 mg/kg/day

Effects on developmental toxicity

Description of key information
7.8.2 Developmental toxicity / teratogenicity: 
KS - Terat.rat. Astroff & Young, 1999. KL.2, NOAEL Maternal and offspring 15 mg/kg/day
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
15 mg/kg bw/day
Additional information

In the developmental rat study (Astroff & Young, 1999) again effects on body weight were observed, with the maternal NOAEL considered to be 15 mg/kg/day. Developmental NOAEL was considered to be 15 mg/kg/day, based on multiple skeletal developmental retardations (including incomplete and unossified bones) observed at higher doses. When these findings are assessed in conjunction with the 2 generation study results, the skeletal retardations are thought not be a lasting adverse effect as foetal viability was not decreased in the 2-generation reproduction study. Furthermore these effects were only observed in the presence of maternal toxicity (reductions in body weight loss), with such effects not associated with any consistent syndrome of developmental effects in the rat (Chernoff, et al., 1988).

Reference:

Chernoff, N., Miller, D.B., Rosen, M.B. & Mattscheck, C.L. (1988). Developmental effects of maternal stress in the CD-1 mouse induced by restraint on single days during the period of major organogenesis. Toxicology., 51., pp 57 -65.

Justification for classification or non-classification

Developmental effects were only observed in the presence of maternal toxicity. No evidence of fertility effects were observed. Therefore amicarbazone has not been classified as teratogenic or causing an adverse effect on fertility.