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Effects on fertility

Description of key information

No toxicity data on adverse effects on sexual function and fertility with zinc neodecanoate basic are available, thus the reproductive toxicity will be addressed with existing data on the individual assessment entities zinc and neodecanoate.

Zinc neodecanoate basic is not expected to impair sexual function and fertility, since the two assessment entities zinc and neodecanoate have not shown adverse effects on fertility.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

Zinc

The reproductive toxicity of zinc compounds has been investigated in one and two generation reproductive toxicity studies in which rats or mice were dosed by gavage or via the diet with soluble zinc compounds (i. e., zinc chloride, zinc sulphate) at exposure levels up to 14 mg Zn/kg bw/day (gavage) or 200 mg Zn/kg bw/day (diet) (Khan et al., 2001, 2003, 2007; Samanta et al, 1986). Further information on potential effects of zinc compounds on male or female reproductive organs could be retrieved from subchronic toxicity studies as conducted by Maita et al. (1981) and Edwards and Buckley (1995).

 

The available information suggests that high oral doses of zinc (i. e., exposure levels greater than 20 mg Zn/kg bw/day) may adversely affect spermatogenesis and result in impaired fertility indicated by decreased number of implantation sites and increased number of resorptions (US EPA, 2005). However, these effects were only observed in the presence of maternal toxicity as seen in the one or two generation studies conducted by Khan et al. (2001, 2003, 2007) or, in case of the study conducted by Kumar et al. (1976), when other study non-zinc relevant study specificities could have impacted the study outcome.

In a large number of controlled trials, dietary supplementation with zinc rate of 20 mg/day and 30 mg/day did not result in any adverse reproductive effects in healthy pregnant women as summarised in WHO (2001) and ATSDR (2005).

Neodecanoate

In a modified three-generation reproductive toxicity study, male and female Sprague-Dawley rats were administered neodecanoic acid at 0, 100, 500 and 1500 ppm (approximately 0, 5, 25 and 75 mg/kg-bw/day, respectively) in the diet. No adverse effects were observed on survival, appearance, behaviour, body-weight gain and food consumption in the parental, F1 or F2 generations. The reproductive performance of the parents was not affected. No treatment-related gross or microscopic pathological findings were observed at any of the dietary levels.

 

No classification for reproductive or developmental toxicity is indicated according to the classification, labelling and packaging (CLP) regulation (EC) No 1272/2008.

 

Zinc neodecanoate basic

Since no reproductive toxicity study is available for zinc neodecanoate basic, information on the individual assessment entities zinc and neodecanoate will be used for the hazard assessment of zinc neodecanoate basic. For the purpose of hazard assessment, the point of departure for the most sensitive endpoint of each assessment entity will be used for the DNEL derivation. In case of neodecanoic acid in zinc neodecanoate basic, the NOAEL of 75 mg/kg bw/day for the reproductive toxicity will be used. For zinc the NOAEL of 0.83 mg/kg bw/day (human data) will be used. For further information on the toxicity of the individual assessment entities, please refer to the relevant sections in the IUCLID and CSR.

Effects on developmental toxicity

Description of key information

No toxicity data on adverse effects on development of the offspring with zinc neodecanoate basic are available, thus the reproductive toxicity will be addressed with existing data on the individual assessment entities zinc and neodecanoate.

Zinc neodecanoate basic is not expected to impair development, since the two assessment entities zinc and neodecanoate have not shown adverse effects on development.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available

Toxicity to reproduction: other studies

Additional information

Zinc

The developmental toxicity of zinc compounds can be assessed on the basis of prenatal toxicity studies that have been conducted with soluble zinc sulphate and zinc chloride and slightly soluble zinc carbonate in rats, mice, hamsters or rabbits. Moreover, a total of three (one or two generation) reproductive toxicity studies conducted by Khan et al.(2001, 2003, 2007) provide further information on potential teratogenic effects of zinc compounds.

No prenatal toxicity was observed with either zinc sulphate, zinc chloride or zinc carbonate at exposure levels up to 50 mg Zn/kg bw/day by oral gavage or 200 mg Zn/kg bw/day if the zinc was dosed via the diet. Established NOAELs in these studies were typically at highest dose tested and systemically tolerated by the dams. Developmental effects such as decrease in body or organ weights were, however, observed in F1 and/or F2 generations in the one or two generation reproductive toxicity studies conducted by Khan et al. (2001, 2003, 2007). These studies are not considered suitable for the assessment of teratogenic effects for hazard classification or risk assessment purposes since they were always observed in the presence of maternal toxicity.

 

Neodecanoate

In a modified three-generation reproductive toxicity study, male and female Sprague-Dawley rats were administered neodecanoic acid at 0, 100, 500 and 1500 ppm (approximately 0, 5, 25 and 75 mg/kg-bw/day, respectively) in the diet. No adverse effects were observed on survival, appearance, behaviour, body-weight gain and food consumption in the parental, F1 or F2 generations. The reproductive performance of the parents was not affected. No treatment-related gross or microscopic pathological findings were observed at any of the dietary levels.

 

In a prenatal developmental toxicity study, pregnant rats, n=22 per dose, were treated by oral gavage to 50, 250, 600 or 800 mg/kg/day Neoheptanoic acid during gestation days 6-15. On gestation day 21, the dams were euthanized and the pups were examined for signs of developmental toxicity. Under the conditions of the experimental methods, the test material produced maternal toxicity at dose levels of 600 and 800 mg/kg with maternal lethality at 800 mg/kg. The test material was severely embryotoxic at 800 mg/kg with less than 20% of embryos surviving. Offspring of the 800 mg/kg group had reduced body weight, reduced crown-rump distance, displayed variations signifying delayed development, and a significant percentage (25%) were malformed. In the 600 mg/kg group, there was an increase number of dams with 3 or more resorptions. Offspring of the 600 mg/kg group displayed significant incidences of major (hydrocephalus) and minor (knobby or angular ribs, extra lumbar vertebrae) malformations but showed few signs of delayed development and were not runted. There was no statistically significant evidence of maternal toxicity at dose levels of 50 or 250 mg/kg. There was a slight, but not statistically significant, increase in embryonic resorption noted for the 250 mg/kg group. There was no statistically significant evidence of developmental toxicity at doses for 50 or 250 mg/kg. The NOAEL for maternal toxicity is 600 mg/kg and the NOAEL for developmental toxicity is 250 mg/kg. 

 

No classification for reproductive or developmental toxicity is indicated according to the classification, labelling and packaging (CLP) regulation (EC) No 1272/2008.

Zinc neodecanoate basic

Since no reproductive toxicity study is available for zinc neodecanoate basic, information on the individual assessment entities zinc and neodecanoate will be used for the hazard assessment of zinc neodecanoate basic. For the purpose of hazard assessment, the point of departure for the most sensitive endpoint of each assessment entity will be used for the DNEL derivation. In case of neodecanoic acid in zinc neodecanoate basic, the NOAEL of 75 mg/kg bw/day for the reproductive toxicity will be used. For zinc the NOAEL of 0.83 mg/kg bw/day (human data) will be used. For further information on the toxicity of the individual assessment entities, please refer to the relevant sections in the IUCLID and CSR.

Justification for classification or non-classification

Zinc neodecanoate basic is not expected to impair fertility or development, since the two moieties zinc and neodecanoate have not shown adverse effects in reproduction or prenatal developmental toxicity studies. No classification for toxicity to reproduction is indicated according to (EC) No 1272/2008 and its subsequent amendments.

Additional information

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