Hexadecyl hydrogen maleate

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

No effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

55 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

The effects of the substance on fertility was evaluated by considering data on the similar substance 02 and 03. Justification for Read Across is given in Section 13 of IUCLID.

In the study available for Similar Substance 02, no effects on the reproductive organs were observed. Fertility assays did not reveal any adverse reproductive effects. Furthermore, examination of the reproductive organs in a number of repeated-dose studies did not show evidence indicative of adverse reproductive changes. Overall, there are no concerns that the substance might adversely affect fertility.

The effects of Similar Substance 03 on the reproduction in CD rats were evaluaed in a multigeneration study. Rats (10 males and 20 females/group) received 0, 20, 55 or 150 mg/kg/day of substance in corn oil orally and were mated to produce two generations, each with two litters. Groups of the same size from the second litter were used for sebsequent generations and were given the same dose of the test substance as were their parents. The high-dose group was terminated during the second generation due to treatement related mortality in adults. Rean cortical necrosis occured in high-dose F0 males and females. Increased kidney weights were observed in low- and mid-dose adult F1 females. No treatment-related effects on reproduction were observed at doses up to 55 mg/kg/day over two generations. No NOAEL was determined in the study but it can be extrapolted to be 55 mg/kg bw/day for general toxicity, while the NOAEL for reproductive toxicity should be > 150 mg/kg bw/day which is the highest tested concentration.

Overall, the substance is not expected to exert any toxicity to reproduction.

Effects on developmental toxicity

Description of key information

Not a developmental toxicant.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

140 mg/kg bw/day

Study duration:

subacute

Species:

rat

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

The developmental toxicity of the substance was evaluated based on data on Similar Substance 03. Justification for Read Across is given in Section 13 of IUCLID.

The effects of the substance on the develoment in CD rats were evaluated. Pregnant rats received 0, 30, 90 or 140 mg/kg/day of test material in corn oil orally from Days 6 -15 of gestation and fetuses were examined for gross soft tissue and skeletal deffects.

Maternal toxicity was demonstrated by the failure of dams to gain weight between Days 6 and 9 of gestation. Larger doses of test material would have had more severe effects on weight gain and probably would have produced mortality, thus compromising the present study. In the teratology stduy, dams were treated orally with up to 140 mg/kg/day from day 6 to day 15 of gestation. An examination of fetuses did not reveael any effects that were attributed to the test material. No increase in fetal malformations was observed, and the variations detected were similar in control and treated groups. Under the conditions of the study, no treatment-related effects on fetal development were observed and thus it is concluded that the substance is not teratogenic. A NOAEL was not reported in the study. Considering the results obtained a NOAEL (maternal) was extrapolated as 140 mg/kg bw/day.

Justification for classification or non-classification

No significantly adverse effects were observed during the available studies.

According to the CLP Regulation (EC) No. 1272/2008, the following categories for reproductive toxicants are available:

- Category 1: Known or presumed human reproductive toxicant - Substances are classified in Category 1 for reproductive toxicity when they are known to have produced an adverse effect on sexual function and fertility, or on development in humans or when there is evidence from animal studies, possibly supplemented with other information, to provide a strong presumption that the substance has the capacity to interfere with reproduction in humans. The classification of a substance is further distinguished on the basis of whether the evidence for classification is primarily from human data (Category 1A) or from animal data (Category 1B).

- Category 1A: Known human reproductive toxicant - The classification of a substance in this Category 1A is largely based on evidence from humans.

- Category 1B: Presumed human reproductive toxicant - The classification of a substance in this Category 1B is largely based on data from animal studies. Such data shall provide clear evidence of an adverse effect on sexual function and fertility or on development in the absence of other toxic effects, or if occurring together with other toxic effects the adverse effect on reproduction is considered not to be a secondary nonspecific consequence of other toxic effects. However, when there is mechanistic information that raises doubt about the relevance of the effect for humans, classification in Category 2 may be more appropriate.

- Category 2: Suspected human reproductive toxicant - Substances are classified in Category 2 for reproductive toxicity when there is some evidence from humans or experimental animals, possibly supplemented with other information, of an adverse effect on sexual function and fertility, or on development, and where the evidence is not sufficiently convincing to place the substance in Category 1. If deficiencies in the study make the quality of evidence less convincing, Category 2 could be the more appropriate classification. Such effects shall have been observed in the absence of other toxic effects, or if occurring together with other toxic effects the adverse effect on reproduction is considered not to be a secondary non-specific consequence of the other toxic effects.

 

The substance is not classified as a Reproductive toxicant since no adverse effects on sexual function, fertility or on development occurred during the available studies.