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Key value for chemical safety assessment

Effects on fertility

Description of key information

No toxicity data on adverse effects on sexual function and fertility with zinc ditetradecanoate are available, thus the reproductive toxicity will be addressed with existing data on the entities formed upon dissolution of zinc ditetradecanoate, namely zinc and tetradecanoate. All available information on the two entities zinc and tetradecanoic acid do not indicate any effects on the impairment of male or female 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).

Tetradecanoic acid

According to Regulation (EC) No 1907/2006 Annex V substances obtained from natural sources and not modified such as vegetable fats and oils as well as fatty acids from C6 to C24 and their potassium, sodium, calcium and magnesium salts are excluded from the obligation to register. Tetradecanoate is a common saturated C14- fatty acid, which is present in bovine milk, breast milk as well as palm kernel oil, coconut oil and butterfat.

 

The long history of safe use of these acids and their related glycerides and food oils, as well as the GRAS status for several of the fatty acids and their salts, indicate the low potential for reproductive toxicity of these substances.

According to the HERA document on fatty acid salts a “three-generation reproductive study on a C10 fatty did not produce any reproductive effects (Hendrich et al. (1993)). No effects on gonads weights, and no gross or histopathological findings for testes, seminal vesicle, ovary, uterus, or prostate were observed in a 90 day study with 9-Octadecanoic acid. The NOAEL for reproductive effects was 14,000 mg/kg bw, the highest dose tested” (OECD SIDS, 2014).

 

Based on evaluation of a wealth of human medical and nutritional data and the fact that tetradecanoic acid is an essential human and animal nutrient, it is concluded that tetradecanoic acid, does not pose any hazard for reproduction and/or developmental toxicity. In conclusion, the conduct of any further reproductive toxicity studies in animals would not contribute any new information and is therefore not considered to be required.

 

Zinc tetradecanoate

Since no reproductive toxicity study is available specifically for zinc ditetradecanoate, information on the individual constituents zinc and tetradecanoic acid will be used for the hazard assessment and when applicable for the risk characterisation of zinc ditetradecanoate. Naturally occurring fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (cf REACH Annex V (Regulation (EC) No 987/2008)). Based on the hazard data for the individual moieties of zinc ditetradecanoate provided above, zinc ditetradecanoate is not expected to impair fertility.

Effects on developmental toxicity

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

Justification for classification or non-classification

Zinc ditetradecanoate is not expected to impair fertility, since the two moieties zinc and tetradecanoate have not shown adverse effects on fertility. Further testing is not required. For further information on the toxicity of the individual assessment entities, please refer to the relevant sections in the IUCLID and CSR. No information on the developmental toxicity of the moieties zinc and tetradecanoic acid is available, thus no final conclusion on classification and labelling can be made.