Zinc 3,5,5-trimethylhexanoate

Endpoint summary

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 bis(3,5,5-trimethylhexanoate) are available, thus the reproductive toxicity will be addressed with existing data on the individual moieties zinc and 3,5,5-trimethylhexanoic acid. According to the RAAF, neodecanoic acid will be considered in place of 3,5,5-trimethylhexanoic acid.

Zinc bis(3,5,5-trimethylhexanoate) is not expected to impair fertility, since the two moieties zinc and, 3,5,5-trimethylhexanoic acid, as represented by neodecanoic acid, have not shown adverse effects on fertility.No information on the developmental toxicity of the moiety3,5,5-trimethylhexanoic acid or its representativeneodecanoic acid are available, thus no final conclusion on classification and labelling can be made.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No toxicity data on adverse effects on sexual function and fertility with zinc bis(3,5,5-trimethylhexanoate) are available, thus the reproductive toxicity will be addressed with existing data on the individual moieties zinc and 3,5,5-trimethylhexanoic acid, as represented by neodecanoic acid.

 

 

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 sub-chronic 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).

 

 

Neodecanoic acid

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 bis(3,5,5-trimethylhexanoate)

Since no reproductive toxicity study is available for zinc bis(3,5,5-trimethylhexanoate), information on the individual moieties zinc and3,5,5-trimethylhexanoic acid, as represented by neodecanoic acid,will be used for the hazard assessment of zinc bis(3,5,5-trimethylhexanoate).For the purpose of hazard assessment of zincbis(3,5,5-trimethylhexanoate), the point of departure for the most sensitive endpoint of each moiety will be used for the DNEL derivation. In case of 3,5,5-trimethylhexanoic acid, as represented by neodecanoic acid, in zincbis(3,5,5-trimethylhexanoate), 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.

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

Due to an absence of adverse effects seen in the reproductive toxicity tests with zinc and neodecanoic acid, as representative of 3,5,5-trimethylhexanoic acid, a classification for reproductive toxicity in accordance with regulation (EC) 1272/2008 is not warranted.

No information on the developmental toxicity of the moiety neodecanoic acid is available, thus no final conclusion on classification and labelling can be made.