Cyclohexane, oxidized, aq. ext.

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Additional information

Cyclohexane, oxidized, aquous extract and it's analog read-across substance, adipic acid, have not been tested with a focus on toxicity to reproduction. In accordance with Section 3 of Annex VI and for reasons of animal welfare, the study does not need to be conducted because exposures to the substance will be minimal on the basis that the substance is [to be] placed on the market as a monomer in an imported polymer and/or as an imported monomer that will be handled under strictly controlled conditions in that it is rigorously contained by technical means during its whole lifecycle. Control and procedural technologies are [will be] used to minimise emission and any resulting exposure.

 

Read Across (Adipic Acid):

Hazards identified by OECD/ICCA high production volume chemicals program in 2004:

"Fertility assessment: No specific studies on fertility have been conducted. In a two-years feeding study in rats histopathological examination of testes, ovaries, and uterus revealed no evidence of an adverse effect on the reproductive organs up to the highest doses tested (males approx. 3750 mg/kg bw/day, females approx. 750 mg/kg bw/day). Based on the available data there is no reason to expect specific reproductive toxicity of adipic acid."

As confirmed by recent literature (Mangelsdorf et al 2003, Ulbrich & Palmer 1995, Janer et al 2007a, Dent 2007, Sanbuissho et al. 2009) in rodents histopathological examinations in repeated dose toxicity studies of reproductive tissues are of high value and high sensitivity for evaluation of reproductive toxicity in males and females. Histopathological changes on the reproductive organs in repeated dose toxicity studies are indicative of effects on fertility. With this respect repeated dose toxicity studies should be considered sensitive and sufficient information to evaluate toxicity on fertility if histological examination of the reproductive organs is covered.

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- Mangelsdorf. et al., 2003: Some aspects relating to the evaluation of the effects of chemicals on male fertility. Regulatory toxicology and Pharmacology 36, 69-98

- Ulbrich & Palmer, 1995: Detection of effects on male reproduction – a literature survey. J am. College of Toxicology 14, 293-327

- Janer et al., 2007: A retrospective analysis of the added value of the rat two-generation reproductive toxicity study versus the rat subchronic toxicity study. Reproductive Toxicology 24, 103-113

- Dent, 2007: Strength and limitations of using repeated-dose toxicity studies to predict effects on fertility. Regulatory Toxicology and Pharmacology 48, 241-258

- Sanbuissho et al., 2009: Collaborative work on evaluation of ovarian toxicity by repeated-dose and fertility studies in female rats. J Tox. Sci. 34:Special Issue SP1-SP22

Short description of key information:

In accordance with Section 3 of Annex VI and for reasons of animal welfare, the study does not need to be conducted because exposures to the substance will be minimal on the basis that the substance is [to be] placed on the market as a monomer in an imported polymer and/or as an imported monomer that will be handled under strictly controlled conditions in that it is rigorously contained by technical means during its whole lifecycle. Control and procedural technologies are [will be] used to minimise emission and any resulting exposure.  Furthermore, based on the repeated dose toxicity studies on the analog read-across substance, adipic acid, we concur with the conclusion of the OECD/ICCA high production volume chemicals program (2004): "Fertility assessment:  No specific studies on fertility have been conducted. In a two-years feeding study in rats histopathological examination of testes, ovaries, and uterus revealed no evidence of an adverse effect on the reproductive organs up to the highest doses tested (males approx. 3750 mg/kg bw/day, females approx. 750 mg/kg bw/day). Based on the available data there is no reason to expect specific reproductive toxicity of adipic acid."

Effects on developmental toxicity

Description of key information

In limited studies, the anolog read-across substance, adipic acid, was not embryo- or fetotoxic and not teratogenic after oral administration to rats, mice, and rabbits.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Additional information

Cyclohexane, oxidized, aquous extract has not been tested with a focus on developmental toxicity.

Read Across (Adipic Acid):

Hazards identified by OECD/ICCA high production volume chemicals program in 2004:

"Adipic acid was not embryo- or fetotoxic and not teratogenic after oral administration to rats, mice, and rabbits. NOAELs for rat, mouse and rabbit are 288, 263, and 250 mg/kg bw/day, respectively, the highest doses tested. In none of these studies signs of maternal toxicity have been observed and the highest dose was well below the limit dose of 1000 mg/kg bw which would be a precondition for a valid negative study. In view of the low systemic toxicity of the compound, however, this endpoint seems to be adequately covered despite the limitations of the studies."

Updated relevant information:

None

Toxicity to reproduction: other studies

Additional information

A multi-generation reproduction toxicity study is not available. Based on the considerations above no further testing is required as adipic acid has not shown specific effects on reproductive organs in male and female rats and there was no evidence of a specifc reproductive toxicity of adipic acid in a developmental toxicity studies.

Justification for classification or non-classification

Adipic acid is not toxico to reproduction; no classification is required according to the EU classification criteria 67/548/EWG and regulation no. 1272/2008 (GHS).