4-O-α-D-glucopyranosyl-D-glucitol

Endpoint summary

Key value for chemical safety assessment

Effects on developmental toxicity

Additional information

In accordance with Annex VII of REACh (Regulation (EC) No 1907/2006), the assessment of the developmental/teratogenicity toxicity of the substance is not required. However, two available data were reported in this endpoint for Maltitol, as any other relevant physicochemical, toxicological and ecotoxicological information that is available shall be provided according to REACh (Regulation (EC) No 1907/2006), Annex VII.

No key developmental toxicity data is available for the substance Maltitol. Only 2 supporting data were available.

The first study is a publication (Canimoglu S and Rencuzogullari E, 2012; non GLP; not compliant with current guidelines; Reliability 2). In this study, pregnant female rats were intraperitoneally treated with 1, 2 and 4 g/kg bw/day concentrations of Maltitol during the first 7 days of gestation (Gestation day 1 to 7; first trimester) to investigate the teratogenicity of maltitol. Fetuses were collected after killing the dams by cervical dislocation under ether anaesthesia on gestation day 19. The results of this study showed that, under the experimental conditions of the test, maltitol was not teratogenic but decreased the fetuses weight and at the highest dose (4 g/ kg bw) caused growth retardation.

In this study, the treatment period was limited to the first trimester of gestation instead of at least from implantation to one day prior to the day of scheduled kill, which should be as close as possible to the normal day of delivery. In addition, the intraperitoneal route was used instead of the currently recommend ed oral route and high doses were used (top dose of 4000 mg/kg bw/day). Based on the above, this study could not be considered as a key study as it does not fully comply with current teratogenicity testing standards. However, as the study was well conducted and documented, it still provides useful information on the teratogenic potential of the registered substance. Therefore, it was considered as a supporting study for the developmental/teratogenicity endpoint.

The second study is a peer reviewed data (CIR, 2008; Reliability 4). In this study, the authors reported on the effects of Maltitol in gravid female rabbits. Maltitol was administered orally by gavage to the animals from gestation day 6 through day 18 of pregnancy at doses of 1.25, 2.5, or 5 g/kg/day. At the highest dose tested (5 g/kg/day), there was an increase in the number of early resorptions and increased post-implantation losses. No effects were observed in any treated group on maternal body weight increase, number of viable and dead fetuses, or on fetal body weights. In addition, no malformed fetuses were found at any of the doses administered. No further details on the study design or results were reported in the CIR report and the original study was not available for review. Thus, this data was also considered as supporting.