Fatty acids, C18-24, zinc salts

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No reproductive toxicity study with substance Fatty acids, C18-24, zinc salts is available, thus the reproductive toxicity will be addressed with existing data on the entities formed upon dissolution of substance Fatty acids, C18-24, zinc salt, namely zinc and fatty acids, C18-24. Substance Fatty acids, C18-24, zinc salts is not expected to impair sexual function or fertility, since the two moieties zinc and fatty acids, C18-24 are lacking such effects.

Additional information

FATTY ACIDS, C18-24, ZINC SALTS:

No reproductive toxicity study with substance Fatty acids, C18-24, zinc salts is available.

For the assessment of toxicological effects of substance Fatty acids, C18-24, zinc salts a read-across of existing toxicity data of the dissociation products zinc and fatty acids, C18-24 is applied. The hazard assessment is based on the most toxic moiety, i.e. the zinc cation.

Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)).

The zinc cation is selected as most toxic moiety. However, also zinc is not expected to induce really adverse effects in humans. Zinc is essential for human growth and development, neurological functions and immunocompetence. The main clinical manifestations of zinc deficiency are growth retardation, delay in sexual maturation or increased susceptibility to infections (SCF, 2003). Health specialists recommend supplementing the diet with zinc in case human diet is zinc deficient. It can be concluded, that a zinc deficit is more likely associated with adverse effects to fertility than a zinc surplus.

Thus, substance Fatty acids, C18-24, zinc salts is not expected to be toxic to reproduction, since the two moieties zinc and fatty acids, C18-24 are considered non toxic to reproduction. Read-across and conclusion are in line with the conclusion of an EU risk assessment carried out on the structural analogue substance Fatty acids, C16-18, zinc salts (i.e. zinc strearate) within the framework of EU Existing Chemicals Regulation 793/93 (EU RAR Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II–Human Health. EUR 21168 EN (http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1):

„No data were provided on the reproductive toxicity of zinc distearate. Data on other zinc compounds have been used, based on the assumption that after intake the biological activities of the zinc compounds are determined by the zinc cation.

For fertility no 1- or 2-generation or other applicable guideline studies are available. When male rats were dosed with approximately about 200 mg Zn²⁺/kg bw via the food for 30-32 days before mating, a statistically significant reduction in male reproductive performance was observed. This effect was attributed to a reduction in sperm motility. In females receiving 200 mg Zn²⁺/kg bw, reduced conception was observed when they were dosed after mating, but not when they were dosed before and during pregnancy. It is not known whether the reduced sperm motility in males and the contradictory effects on conception in females are a direct effect of zinc on the sperm cells, embryos or uterine function, or whether they are the result of disturbances in other physiological functions. From a study by Schlicker and Cox (1968), it is known that this dose level (and even levels of 100 mg additional Zn²⁺/kg bw/day) may result in impaired copper balance in females.

In repeated dose toxicity studies with zinc sulphate heptahydrate, no effects on the reproductive organs were seen at dose levels up to ca. 1,100 mg and 565 mg Zn²⁺/kg bw/day for mice and rats, respectively. In a repeated dose toxicity study with zinc monoglycerolate hypoplasia of several sex organs was observed at doses of ca. 300 mg Zn2+/kg bw/day, but not at 13 or 60 mg Zn²⁺/kg bw/day. As these effects were only seen at dose levels which produced very severe general toxicity, it is impossible to conclude that these adverse effects are directly related to zinc. It should be noted that these studies are not designed to detect effects on sperm cell motility.

Developmental toxicity studies, according to a study design similar to OECD 414, with mice,rats, hamsters and rabbits were described with unspecified zinc sulphate. These studies do not permit the derivation of a proper NOAEL because neither reproductive nor developmental or maternal effects were observed, not even at the highest dose tested. When it is assumed (worst case) that the heptahydrate was administered from the study with hamsters it can be calculated that the NOAEL for both maternal effects and effects on the offspring is at least 19.9 mg Zn²⁺/kg bw/day. In other (non-guideline) studies, higher dose levels (up to 200 Zn²⁺/kg bw/day) have been reported to result in resorptions and retarded foetal growth, but not in external malformations. No resorptions and growth retardation were seen at 100 mg Zn²⁺/kg bw/day but as the study was too limited, this dose level cannot be taken as an NOAEL for developmental toxicity, either. Besides, at both 100 and 200 mg Zn²⁺/kg bw/day changes in maternal and fetal copper status were observed. In absence of better information a NOAEL of > 19.9 mg Zn²⁺/kgbw/day for developmental toxicity in animals is adopted.

In studies with pregnant women receiving additional 0.3 mg Zn²⁺/kg bw/day (as zinc sulphate or citrate) during the last 6 months of pregnancy, no reproductive or developmental effects were observed. Clear evidence of zinc toxicity in human pregnancy has not been reported but this may be due to the fact that very high exposures to zinc in human pregnancy are unusual. In contrast, zinc deficiency during pregnancy can cause a variety of adverse effects on the foetus or may result in reduced fertility or delayed sexual maturation in animals as well as in humans (Walsh et al., 1994; ATSDR, 1994; WHO, 1996).”

Please refer to the section for the respective assessment entity for data on the moieties. In brief:

ZINC:

Overall weight of evidence suggests that zinc compounds are not hazardous to reproduction.

FATTY ACIDS, C18-24:

Fatty acids are an essential human and animal nutrient. Based on evaluation of a wealth of human medical and nutritional data, it is concluded that fatty acids, C18-24, does not pose any hazard for reproduction toxicity.

Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)).

Effects on developmental toxicity

Description of key information

No developmental toxicity study with substance Fatty acids, C18-24, zinc salts is available, thus the reproductive toxicity will be addressed with existing data on the entities formed upon dissolution of substance Fatty acids, C18-24, zinc salt, namely zinc and fatty acids, C18-24. Substance Fatty acids, C18-24, zinc salts is not expected to have adverse effects to the developing embryo or fetus, since the two moieties zinc and fatty acids, C18-24 are lacking such effects.

Toxicity to reproduction: other studies

Additional information

FATTY ACIDS, C18-24, ZINC SALTS:

No developmental toxicity study with substance Fatty acids, C18-24, zinc salts is available. For the assessment of toxicological effects of substance Fatty acids, C18-24, zinc salts a read-across of existing toxicity data of the dissociation products zinc and fatty acids, C18-24 is applied. The hazard assessment is based on the most toxic moiety, i.e. the zinc cation.

Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)).

The zinc cation is selected as most toxic moiety. However, also zinc is not expected to induce really adverse effects in humans. Zinc is essential for human growth and development, neurological functions and immunocompetence. The main clinical manifestations of zinc deficiency are growth retardation, delay in sexual maturation or increased susceptibility to infections (SCF, 2003). Health specialists recommend supplementing the diet with zinc in case human diet is zinc deficient. Thus, a zinc deficit is more likely associated with adverse effects to the  to the developing embryo or fetus than a zinc surplus.

Thus, substance Fatty acids, C18-24, zinc salts is not expected to be toxic to reproduction, since the two moieties zinc and fatty acids, C18-24 are considered non toxic to reproduction. Read-across and conclusion arein line with the conclusion of an EU risk assessment carried out on the structural analogue substance Fatty acids, C16-18, zinc salts (i.e. zinc stearate) within the framework of EU Existing Chemicals Regulation 793/93 (EU RAR Zinc stearate (CAS# 91051-01-3, CAS# 557-05-1) Part II–Human Health. EUR 21168 EN (http://echa.europa.eu/documents/10162/08799aec-42c5-44e0-9969-baa022c66db1) (see above).

Please refer to the section for the respective assessment entity for data on the moieties. In brief:

ZINC:

Overall weight of evidence suggests that zinc compounds are not hazardous to the developing embryo or fetus.

FATTY ACIDS, C18-24:

Fatty acids are an essential human and animal nutrient. Based on evaluation of a wealth of human medical and nutritional data, it is concluded that fatty acids, C18-24, does not pose any hazard for developmental toxicity.

Fatty acids are generally not considered to represent a risk to humans, which is reflected in their exclusion from REACH registration requirements (c.f. REACH Annex V (Regulation (EC) No 987/2008)).

Justification for classification or non-classification

As the two moieties of substance fatty acids, C18-24, zinc salts do not impair sexual function, fertility or the development of the offspring, substance Fatty acids, C18-24, zinc salts in all probability does also not have reproductive toxic effects.

According to the criteria of REGULATION (EC) No 1272/2008 and its subsequent adaptations, substance Fatty acids, C18-24, zinc salts does not have to be classified and has no obligatory labelling requirement for reproductive toxicity.