D-Glucitol, 1-deoxy-1-(methylamino)-, N-[C8-16 (even numbered) and C18 unsaturated acyl] derivs.

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

150 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

No reproductive toxicity study has been performed with Glucamide CC based on animal welfare considerations. Available data from the structural and biological close analogue Glucamide 24 is used instead. The available data base is considered sufficient for hazard / risk characterization based on a guideline conform one-generation study according to OECD TG 415 with Glucamide 24. No effects on reproductive parameters including sperm motility and all natural delivery and litter parameters were revealed.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Quality of whole database:

The available data base is considered sufficient for hazard / risk characterization independent of the exposure route. There are no indications of adverse effects on reproductive organs or tissues from the available data.

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Quality of whole database:

The available data base is considered sufficient for hazard / risk characterization independent of the exposure route. There are no indications of adverse effects on reproductive organs or tissues from the available data.

Additional information

No reproductive toxicity study has been performed with Glucamide CC based on animal welfare considerations. Available data from the structural and biological close analogue Glucamide 24 is used instead.

The potential effects of Glucamide 24 (Test material 10000506.01, 96.2%) on reproductive function were investigated following OECD TG 415 in a one-generation reproductive study in rats. The test substance was administered once daily via gavage from 70 days prior to mating, during cohabitation (up to 21 days) until the day before sacrifice to 3 groups of rats (25 Crl:CD®(SD)IGS BR VAF/Plus®/sex/dose) at dose levels of 14.8, 147.8, or 344.9 mg/kg bw/day. Males were sacrificed following cohabitation, females were sacrificed on postpartum day 21 and pups were culled on post-natal day (PND) 4 and those maintained were sacrificed on PND 21. Control animals received the vehicle (water) only.

No parental male or female rats died during the course of the study. Clinical observations considered test item related in males treated with 150 and 350 mg/kg bw/day included excess salivation, rales, chromorhinorrhea, red or died red perioral substance and chromodacryorrhea (350 mg/kg bw/day group only). Clinical observation in female rats considered test item related included excessive salivation and rales at 150 and 350 mg/kg bw/day. Though considered treatment and dose related at 150 mg/kg bw/day and above, findings of excess salivation, rales and red or dried red perioral substance were statistically significant in males treated with 350 mg/kg bw/day group as compared to control animals. 

Findings in females treated with 350 mg/kg bw/day were also statistically significant; though the observation of rales was also statistically significant at 150 mg/kg bw/day during the lactation period. Males at the high dose had reduced body weight gain and significantly reduced terminal body weights. Maternal body weight gains and absolute feed consumption were significantly reduced in the 350 mg/kg bw/day group for the entire gestation period. However, there were no effects on the fertility index, mating index, pre-coital index and no significant or biologically relevant differences in the number of the percentage of motile or non-motile sperm.

Differences in the weight of epididymides, testes, seminal vesicles, ovary, uterus, pituitary and brain or the ratios of these organs to the terminal body or brain weights were not observed in the male or females. All natural delivery and litter parameters were unaffected by dosages of the test substance as high as 350 mg/kg bw/day. Clinical and necropsy observations in the F1 generation pups revealed no differences between the dosed groups versus the control. Additionally, substance-related microscopic changes in the brain, pituitary or reproductive organs were not revealed. Based on the data, the NOAEL with regard to reproductive and developmental effects was considered to be greater 350 mg/kg bw/day (corrected value 344.9 mg/kg bw/day). The NOAEL for parental toxicity is considered to be 147.8 mg/kg bw/day, based effects on body weight and food consumption. Clinical effects observed at this and the highest dose were considered indicative of gavage (bolus) administration of a substance with irritating properties. 

Short description of key information:
Relevant information regarding the endpoint reproductive toxicity is available from a guideline conform OECD TG 415 study with the structural and biological close analogue Glucamide 24. Based on the results, the overall NOAEL with regard to reproductive effects is considered to be >= 350 mg/kg body weight per day.

Justification for selection of Effect on fertility via oral route:
Guideline study according to GLP. No derivations and/or confounders. Klimisch rating 1 representing reliability without restrictions. Information is valid and meet data requirements.

Effects on developmental toxicity

Description of key information

Developmental toxicity data following OECD TG 414 are not available for Glucamide CC. However, a guideline conform OECD 414 Segment II study with the structural and biological close analogue Glucamide 24 has not revealed developmental or reproductive toxic effects at any dose level tested. 

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

363 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

No developmental toxicity study has been performed with Glucamide CC based on animal welfare considerations. Available data from the structural and biological close analogue Glucamide 24 is used instead. The available data base is considered sufficient for hazard / risk characterization based on a guideline conform developmental toxicity study according to OECD TG 414 with Glucamide 24. No effects on reproductive parameters including sperm motility and all natural delivery and litter parameters were revealed.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Quality of whole database:

The available data base is considered sufficient for hazard / risk characterization independent of the exposure route. There are no indications of adverse developmental effects and/or effects on reproductive organs or tissues from the available data.

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Quality of whole database:

The available data base is considered sufficient for hazard / risk characterization independent of the exposure route. There are no indications of adverse developmental effects and/or effects on reproductive organs or tissues from the available data.

Additional information

No reproductive toxicity study has been performed with Glucamide CC based on animal welfare considerations. Available data from the structural and biological close analogue Glucamide 24 is used instead.

An OECD 414 Segment II study was performed with Glucamide 24 on 3 groups of 25 rats to determine the developmental toxicity of including teratogenic potential of Glucamide 24 (Test material SS0001.01, 45% active). Analytically determined dosage levels of 15, 150, or 363 mg a.i./kg bw/day were orally administered via gavage as a single daily dose on gestation days (GD) 6 through 15. The control group received the vehicle (water) only. Animals were sacrificed on GD20. Maternal toxicity included clinical signs (material around nose and/or mouth, post-dose increased salivation and decreased activity) and significant reduction in body weight gain observed at the highest dose level of 363 mg/kg bw/day. However, no developmental or reproductive toxic effects were observed at any dose level. The NOAEL for maternal toxicity was considered to be 150 mg a.i./kg bw/day, whereas a NOAEL of greater 363 mg a.i./kg bw/day for developmental toxicity was established. 

Justification for selection of Effect on developmental toxicity: via oral route:
Guideline study according to GLP. No derivations and/or confounders. Klimisch rating 1 representing reliability without restrictions. Information is valid and meet data requirements.

Justification for classification or non-classification

Administration of the read-across compound Glucamide 24 up to maternal toxic doses did not result in any significant changes of reproductive and/or developmental effects. Based hereupon classification and labelling of the registered substance concerning reproductive toxicity is not warranted.