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EC number: 233-162-8
CAS number: 10049-04-4
According to the Column 1 of the REACH
regulation annex VII, an in vitro gene mutation study in bacteria is
required (section 8.4.1).
No reliable bacterial assays for chlorine
dioxide were available. However, chlorine dioxide is a powerful
oxidising agent and is inherently toxic to bacteria as shown by its use
as disinfectant in the drinking water. Considering both the
bacteriostatic effects of the chemical and the availability of the whole
reliable in vitro and the in vivo tests (see below), it is concluded
that the information from a bacterial mutagenic test like the Ames' test
is not be required for the assessment of chlorine dioxide genotoxicity.
Therefore, an in vitro gene mutation study in bacteria using chlorine
dioxide is scientifically unjustified.
the in vitro genotoxicity,
two studies were identified as key study:
mouse lymphoma assay (Cifone, 1986) using mice L5178Y cells gave
positive results for reverse gene mutations.
chromosome aberration assay (Ivett, 1986) performed on CHO cell lines
gave positive results.
conclusion from the results obtained from both of the available in vitro
studies was positive. However, considering the strong reactivity of the
chlorine dioxide, the positive results observed in vitro were likely due
to the in vitro formation of reactive oxygen species which were well
known to be genotoxic. In addition, it is also possible that the
chromosome aberration test included the evaluation of dose levels that
would be considered to be excessively toxic using modern criteria, and
the mouse lymphoma assay would be judged as borderline or equivocal
positive using modern, globally accepted, evaluation criteria. In this
case both results may be considered to be potential false positives
caused by excessive toxicity. Therefore,
it is not possible to conclude on the genotoxicity potential of chlorine
dioxide regarding the in vitro tests only.
three studies were identified as 'key study'.
sister chromatid exchange (SCE) assay (Ivett, 1984) was performed by the
administration of ClO2 intraperitoneally to male mice. SCE
were observed 26 hrs after dosing in the bone marrow tissue of mice. No
significant increase in SCE frequency was observed in any of the dose
groups relative to the negative controls and the frequencies were within
the range of historical controls.
chromosome aberration assay (Ivett, 1984) was performed by the
administration of ClO2 intraperitoneally to mice. Chromosome
aberrations were observed 6, 24 and 48 hrs after dosing in the bone
marrow tissue of mice. No significant increase in the frequency of
chromosomal aberrations was observed.
dominant Rodent lethal assay (Moore, 1984) was performed by the
administration of ClO2 intraperitoneally to mice. Matings
were conducted in order to study the consequences of chromosome
aberrations in germ cells. Chlorine dioxide was not mutagenic, under the
conditions tested, in the mouse dominant lethal assay.
obtained in vitro and in vivo are different. However
according to the ECHA guidance on "information requirements and chemical
safety assessment" (R.7a), the results of in vivo tests
possess a higher degree of reliability. Indeed, the use of immortalized
cell lines such as CHO or L5178Y can give false positive results because
of impaired p53 checkpoint and repair pathway processes. In addition,
the use of modern evaluation criteria for both of the in vitro assays
would likely result in a conclusion of negative, equivocal, or
borderline positive. The results obtained in vitro with chlorine
dioxide can therefore be considered to be false positive, likely
resulting from the reactive oxygen species or from the evaluation of
dose levels exhibiting excessive toxicity. The toxicokinetic data on
chlorine dioxide indicated that chlorine dioxide and its metabolite, the
chlorite, were distributed in the bone marrow. Therefore, the negative
results obtained in vivo after an intraperitoneal administration
of chlorine dioxide cannot be attributed to a lack in target tissue
conclusion, chlorine dioxide is not classified as genotoxic considering
the overall results from the in vivo studies.
Short description of key information:
Mouse lymphoma assay: positive (K, reliability 2)
Chromosome aberration test: positive (K, reliability 2)
Sister chromatid exchange: no significant increase in SCE frequency (K, reliability 2)
Chromosome aberration test: no significant increase in the frequency of chromosomal aberrations (K, reliability 2)
Dominant rodent lethal assay: not mutagenic (K, reliability 2)
Endpoint Conclusion: No adverse effect observed (negative)
The classification entered in the
Annex VI to the CLP Regulation for Chlorine dioxide is not harmonised
for the mutagenicity category.
the above data no additional self-classification is proposed.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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