Copper dichromium tetraoxide

Endpoint summary

Justification for classification or non-classification

Refer to the corresponding section of the CuO and Cr2O3 CSRs.

Copper dichromium tetraoxide is highly insoluble and is not classified following exposure by the oral, dermal or inhalation routes.  For risk assessment purposes, it is assumed to have a similar toxicity profile to copper oxide and chromium (III) oxide, two relatively insoluble copper and chrome (III) substances.

Key information for copper:

Oral route: With regard to the repeat-dose toxicity of copper, the pivotal study was a 90-day study by the oral route with copper sulphate pentahydrate. In rats and mice, ingestion of copper sulphate pentahydrate produced forestomach lesions that could be to the irritant effects of the compound.  The NOAEL for this effect was 16.7 mg Cu/kg bw/day in rats and 97 and 126 mg Cu/kg bw/day in male and female mice respectively. In rats inflammation of the liver was observed.  The NOAELs for liver and kidney damage were 16.7 mg Cu/kg bw/day in rats. The NOAEL for copper was set at 16.7 mg/kg bw/day.

Dermal route: This study is usually required when the dermal route of exposure is significant and the compound is known to be toxic by the dermal route and can penetrate through intact skin. The need to conduct this study with copper or copper compounds must therefore be considered not necessary as although the dermal route of exposure is the most significant route there is no evidence to indicate that copper or copper compounds can cause toxicity or indeed pass through intact skin at significant levels. Acute dermal toxicity studies showed no toxic effects up to and including the highest dose tested. Therefore an accurate and realistic determination of dermal toxicity can be derived from available sub-chronic oral exposure studies, permissible systemic copper levels and in vitro dermal penetration studies on copper and copper compounds.

Inhalation route: A GLP-compliant 28 -day repeat-dose inhalation study was conducted in accordance with OECD Guideline 412, with the addition of a 13 -week recovery period and an evaluation of adaptation to test substance exposure. Additional study endpoints were measurements of copper levels in lung tissue, lung lavage fluid, liver, brain, as well as wet/dry lung weight ratio and clinical chemistry and cytology of bronchoalveolar lavage fluid of all animals.  The study LOEL is 0.2 mg cuprous oxide/m3, as (non-adverse) effects were seen at this dose. The study NOAEL is >= 2 mg/kg cuprous oxide/m3, the highest dose level tested and based on the lack of findings in the lung weight ratio. No STOT classification is proposed from this study as none of the observed effects were considered severe enough to merit classification by the inhalation route.

Key information for chromium(III):

Oral route: A 90-day oral toxicity study was performed at dietary incorporation levels of 2% and 5%; dose levels are calculated to be equivalent to mean achieved intakes of approximately 700 mg/kg bw/d and 2000 mg/kg bw/d, respectively. No clearly treatment-related findings were seen under the conditions of this study. It is therefore concluded that chromium (III) oxide is of very low oral toxicity. Green-coloured faeces noted in the treated groups indicate that the test material was excreted unchanged; findings are consistent with the toxicokinetic data which indicate very limited oral absorption.

Dermal route: No studies of repeated dose dermal toxicity are available and none are proposed. Although the dermal route is relevant to occupational exposure, the absence of effects following the repeated administration of very high oral dose levels of this substance and the negligible dermal absorption mean that toxicity following repeated dermal exposure can confidently be predicted.

Inhalation route: The principle effects observed in a guideline-compliant, 3-month subchronic inhalation study in rats were primarily noted in the respiratory tract. A NOAEC was not established in this study due to the microscopic effects observed in the respiratory tract of some animals, however, the low incidence and minimal severity of the pathological effects suggests that 4.4 mg/m3 is very near a NOAEC for subchronic exposure to chromic oxide.

Specific target organ toxicity – repeated exposure (STOT RE):

Based on the findings in repeat-dose studies included in the copper oxide and chromium oxide CSRs, no classification as STOT-RE under regulation (EC) 1272/2008 is proposed for copper dichromium tetraoxide. No classification or SCLs are considered necessary.