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Description of key information

Repeat dose oral toxicity - waiver

Repeat dose dermal toxicity - waiver

Repeat dose inhalation toxicity: Bowden, A (2005) VAB004; Bowden, A (2005) VAB005; Sohaug, S (2006) (Rat - 72 week)

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
116 mg/m³
Study duration:
subchronic
Species:
rat

Additional information

As carbon monoxide is a gas the oral and dermal routes of exposure are not considered relevant.

In total three repeat dose inhalation toxicity studies have been submitted. The key study (Bowden, 2005 [VAB004]) was conducted with 3 dose (low, mid and high) levels in the rat and the NOEC was the lowest dose 116 mg/m3 [1ppm = 1.145 mg/m3, WHO] tested. Due to haematological effects, myocardial fibrosis, increased heart weights and degenerative changes in the testes and secondary changes in the epidiymides of rats at the mid and high dose groups. The dog study (Bowden, 2005 [VAB005]) has also been submitted as a supporting study.

No adverse effects were observed in the dog study, therefore the highest dose tested was considered the NOEC.

The second study submitted is taken from published data, where female rats were exposed to CO for 20hrs/day, 5 days/week for 72 consecutive weeks. From this study only a single treatment group was used (200ppm). Due to signs of cardiac hypertrophy observed in the treatment group, only a LOAEC could be derived = 200 ppm (229 mg/m3).

Whilst it is important to regconise that only female rats were treated in this study, there are few experimental studies that have been reported in relevant laboratory animals (and are considered robust) that examined subchronic or chronic exposure to CO. Unfortunately, as male animals were not treated in this study, the effects on testes and epididymides following sub-acute exposure to CO could not be further examined. However, despite the incompleteness of the reported data, it is important to stress the only adverse effect observed was limited to cardiac hypertrophy.

Repeated dose toxicity: inhalation - systemic effects (target organ) cardiovascular / hematological: heart; urogenital: epididymides; urogenital: testes

Justification for classification or non-classification

Animal studies have confirmed that target organ toxicity following repeated exposure to carbon dioxide included the heart and the male urogenital system (testes and epididymides) at dose levels of 345 mg/m3and above. Human data confirm CNS, cardiovascular and respiratory effects, with the EU IOELV TWA set at 23 mg/m3. As such, carbon monoxide has been classified as ‘H372 – Causes damage to the heart through prolonged or repeated exposure by inhalation, (Specific target organ toxicity – Repeated exposure [Hazard Category 1])' according to the new CLP classification (EC 1272/2008).