Registration Dossier

Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
genetic toxicity in vivo
Remarks:
Type of genotoxicity: other: various
Type of information:
other: review
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Published review of literature data on the genotoxicity in vivo of manganese compounds

Data source

Reference
Reference Type:
review article or handbook
Title:
DRAFT TOXICOLOGICAL PROFILE FOR MANGANESE
Author:
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Year:
2008
Bibliographic source:
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease Registry

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Review of published literature genotoxiity studies.
GLP compliance:
no
Remarks:
: not relevant
Type of assay:
other: review of various study types

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The ATSDR document reviews the genetic toxicity of various forms of manganese.

Potassium permanganate has been used as a surrogate for sodium permanganate where data are not available. Read-across from potassium permanganate to sodium permanganate is appropriate from the toxicological point of view as the most toxicologically relevant part of the substances is the same (permanganate). The contribution of the sodium/potassium ions to the toxicity of the respective substances is likely to be minimal. The toxicity of both substances is therefore likely to be very similar and will be dominated by local (site of contact) irritant/corrosive effects and systemic toxicity due to the absorption of manganese ions. This toxicophore similarity is adequate justification for waiving the conduct of specific studies with sodium permanganate and the dossier reflects this waiving proposal by including summaries of read-across studies where appropriate.

Test animals

Species:
other: various

Results and discussion

Any other information on results incl. tables

Manganese chloride did not produce somati mutations inDrosophila melanogasterfruit flies in one study, and manganese sulfate did not induce sex-linked recessive lethal mutations in germ cells of maleD. melanogaster. In vivoassays in mice showed that oral doses of manganese sulphate or potassium permanganate caused micronuclei and chromosomal aberrations in bone marrow. In contrast, oral doses of manganese chloride did not cause chromosomal aberrations in the bone marrow or spermatogonia of rats.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): ambiguous
The results of in vitro studies show that at least some chemical forms of manganese have mutagenic potential. However, as the results of in vivo studies in mammals are inconsistent, no overall conclusion can be made about the possible genotoxic hazard to humans from exposure to manganese compounds.
Executive summary:

The ATSDR document represents a comprehensive and up to date review of the genotoxicity of manganese compounds. Manganese chloride did not produce somatic mutations in Drosophila melanogaster fruit flies in one study, and manganese sulfate did not induce sex-linked recessive lethal mutations in germ cells of male D. melanogaster. In vivo assays in mice showed that oral doses of manganese sulphate or potassium permanganate caused micronuclei and chromosomal aberrations in bone marrow. In contrast, oral doses of manganese chloride did not cause chromosomal aberrations in the bone marrow or spermatogonia of rats.

The results of in vitro studies show that at least some chemical forms of manganese have mutagenic potential. However, as the results of in vivo studies in mammals are inconsistent, no overall conclusion can be made about the possible genotoxic hazard to humans from exposure to manganese compounds.