Registration Dossier

Toxicological information

Endpoint summary

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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Additional information

Carbon monoxide is classified as a Category 1 reproductive toxicant (R61 “may cause harm to the unborn child”) and thus the developmental hazard of CO has been adequately assessed. According to the guidance on data requirements for reproductive toxicity the following statement is included in R.8.7.1.

If a substance is known to cause developmental toxicity meeting the criteria for classification as Repr. Cat 1 or 2: R61, and the available data are adequate to support a robust risk assessment, then no further testing for developmental toxicity will be necessary. However, testing for effects on fertility must be considered.”

There are no reports of human epidemiological studies which have investigated potential effects of CO exposure on fertility or sexual function (EHC, 1999; EPA 2010). However, no specific concerns have been raised in reviews of CO toxicity and impacts on human health. As the DNELs for CO are based on occupational health limits derived primarily from human data a specific reproductive toxicity study in animals would be of limited value and is not considered to be justified (see Section 7 Endpoint summary).

References

EHC, 1999. Environmental Health Criteria, 213, International Programme for Chemical Safety, WHO.

EPA, 2010. Integrated Science Assessment for Carbon Monoxide. EPA/600/R-09/019F. January 2010.

Short description of key information:

No suitable studies on carbon monoxide have been identified to address the endpoint of reproductive toxicity  (fertility and sexual function).

Effects on developmental toxicity

Description of key information

Singh, J., Aggison Jr., L., Moore-Cheatum, L. (1993)

Singh, J., Smith, C.B., Moore-Cheatum, L. (1992)

Singh, J., Scott, L.H. (1984).

Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

Carbon monoxide is classified as a Category 1 reproductive toxicant (R61 “may cause harm to the unborn child”) and thus the developmental hazard of CO has been adequately assessed. According to the guidance on data requirements for reproductive toxicity the following statement is included in R.8.7.1.

“If a substance is known to cause developmental toxicity meeting the criteria for classification as Repr. Cat 1 or 2: R61, and the available data are adequate to support a robust risk assessment, then no further testing for developmental toxicity will be necessary. However, testing for effects on fertility must be considered.”

Developmental toxicity associated with CO exposure has been reported in a wide range of animal studies (EHC, 1999; EPA, 2010). Although there are a number of developmental toxicity studies in rodents, and to a limited extent in rabbits, very few are considered suitable for regulatory submission.There are currently no data which satisfy the requirements for a developmental toxicity study in the rabbit. The existing mouse developmental toxicity studies (which have been included in this submission) show carbon monoxide to cause embryo-lethality, feototoxicity and to be teratogenic in the absence of overt maternal toxicity and so an additional study in the rabbit will not identify a more adverse effect. Even if the NOAEL was lower in a rabbit study it is difficult to see how this information would be used as the DNELs for CO are derived from human data (see Section 7 Endpoint summary). Therefore, further studies on the developmental toxicity of CO are not required.

References

EHC, 1999. Environmental Health Criteria, 213, International Programme for Chemical Safety, WHO.

EPA, 2010. Integrated Science Assessment for Carbon Monoxide. EPA/600/R-09/019F. January 2010.

Justification for classification or non-classification

Non-human reproduction/developmental data confirm that carbon monoxide was found to cause a) a reduction in foetal bodyweight and increases in both gross and skeletal malformations at doses of 65 ppm and greater with b) no adverse maternal effects observed. Furthermore, limited epidemiologic evidence has shown that carbon monoxide exposure during pregnancy is associated with increased risk of preterm birth. The heart is known to be a target for carbon monoxide effects in utero, with two studies in particular reporting carbon monoxide associated cardiac birth defects following material exposure. As such, carbon monoxide has been classified as ‘’H360 – May damage fertility or the unborn child’ according to the new CLP classification (EC 1272/2008).