ALFERROCK

Genetic toxicity: in vivo

Administrative data

Endpoint:

genetic toxicity in vivo, other

Remarks:

review article - results of various in vitro and in vivo studies are reported

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Cross-reference

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

genetic toxicity in vivo, other

Remarks:

review article - results of various in vitro and in vivo studies are reported

Type of information:

other: Scientific review

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

Various studies cited in a review article

GLP compliance:

not specified

Type of assay:

other: Various studies cited in a review article

Various studies cited in a review article.

Conclusions:

Based on the results evaluated in a weight-of-evidence approach it can be stated that aluminium compounds are not genotoxic in the absence of cytotoxicity.

Executive summary:

In a review article by Krewski et al., 2007 several in vivo studies regarding the genotoxic potential of aluminum compounds are summarized. For aluminum chloride and aluminum sulfate the results of 2 studies each depicts a similar picture as the in vitro tests, with observed genotoxicity upon high dosage levels, but not upon lower doses. The 2 studies with aluminum sulfate were performed by Roy et al., 1992 and Dhir et al., 1993 using between 100-500 mg/kg bw. The author reported an increase in micronucleated polychromatic peripheral erythrocytes 24 hours after a second aluminum dose of 500 mg/kg bw but not upon 250 mg/kg bw. Dhir et al., 1993 reported sister chromatid exchange, detected by bromodeoxyuridine, 24 hours after injection in male Swiss albino mice. For aluminum chloride, positive findings were reported in a preliminary study by Manna and Das, 1972 using 10-100 mmol/mouse i.p. causing chromosome aberrations. In contrast, Spotheim-Maurizot et al., 1992 did not observe genotoxic effects of aluminum chloride upon doses of 0.2 mM.

A short term study using aluminum nitrilotriacetate complex administered i.p. at a dosage of 7 mg/Al/kg caused no changes in the formation of 8-hydroxydeoxyguanosie within 24-48 hours (Umemura et al., 1990). A 1.2% aluminum clofibrate content in the diet of F-344 rats raised within 1 -12 month the hepatic peroxisomal beta-oxidation enzyme activity. Such effects are known for clofibrate, and therefore are not related to aluminum (Takagi et al., 1990).

Some other positive findings are summarized in the review of Krewski et al., 2007 in which complex mixtures that entailed aluminum were analyzed. These positive findings may, however, rather relate to the non-aluminum fractions of the mixtures. In the study by Bauer et al., 1995 vacuum pump oils contaminated with waste products from a BC13/C12 aluminum plasma etching process were given to female Wistar rats and the approximated aluminum concentration was only 2000 ppb. Another mixture study was performed by Sivikova and Dianovsky, 1995 administering ionic forms of metals from an aluminum refining plant in distilled water for one year to sheep. The total aluminum concentration delivered was 1.1 or 2.4 mmol/Al/animal/day. Only the higher dose resulted in an increase of sister chromatid exchanges in the cultures lymphocytes.

Thus, in summary of the reported studies using various aluminum compounds, the author stated, that in agreement with their non-carcinogenic activity, aluminum compounds failed to show positive results in most short-term and animal experiments to determine genotoxic potential of aluminum compounds lead to contradictory results with a suggestion of an anti-genotoxic potential.

Materials and methods

Test material

Test material information

Constituent 1

Reference substance name:

Neutralisation and reduction products of bauxite residue from refinement process

Molecular formula:

The substance is a UVCB for which it is not possible to provide a molecular formula and a molecular weight.

IUPAC Name:

Neutralisation and reduction products of bauxite residue from refinement process

Test material form:

solid

Results and discussion

Any other information on results incl. tables

Various studies cited in a review article.

Applicant's summary and conclusion

Conclusions:

Based on the results evaluated in a weight-of-evidence approach it can be stated that aluminium compounds are not genotoxic in the absence of cytotoxicity.

Executive summary:

In a review article by Krewski et al., 2007 several in vivo studies regarding the genotoxic potential of aluminum compounds are summarized. For aluminum chloride and aluminum sulfate the results of 2 studies each depicts a similar picture as the in vitro tests, with observed genotoxicity upon high dosage levels, but not upon lower doses. The 2 studies with aluminum sulfate were performed by Roy et al., 1992 and Dhir et al., 1993 using between 100-500 mg/kg bw. The author reported an increase in micronucleated polychromatic peripheral erythrocytes 24 hours after a second aluminum dose of 500 mg/kg bw but not upon 250 mg/kg bw. Dhir et al., 1993 reported sister chromatid exchange, detected by bromodeoxyuridine, 24 hours after injection in male Swiss albino mice. For aluminum chloride, positive findings were reported in a preliminary study by Manna and Das, 1972 using 10-100 mmol/mouse i.p. causing chromosome aberrations. In contrast, Spotheim-Maurizot et al., 1992 did not observe genotoxic effects of aluminum chloride upon doses of 0.2 mM.

A short term study using aluminum nitrilotriacetate complex administered i.p. at a dosage of 7 mg/Al/kg caused no changes in the formation of 8-hydroxydeoxyguanosie within 24-48 hours (Umemura et al., 1990). A 1.2% aluminum clofibrate content in the diet of F-344 rats raised within 1 -12 month the hepatic peroxisomal beta-oxidation enzyme activity. Such effects are known for clofibrate, and therefore are not related to aluminum (Takagi et al., 1990).

Some other positive findings are summarized in the review of Krewski et al., 2007 in which complex mixtures that entailed aluminum were analyzed. These positive findings may, however, rather relate to the non-aluminum fractions of the mixtures. In the study by Bauer et al., 1995 vacuum pump oils contaminated with waste products from a BC13/C12 aluminum plasma etching process were given to female Wistar rats and the approximated aluminum concentration was only 2000 ppb. Another mixture study was performed by Sivikova and Dianovsky, 1995 administering ionic forms of metals from an aluminum refining plant in distilled water for one year to sheep. The total aluminum concentration delivered was 1.1 or 2.4 mmol/Al/animal/day. Only the higher dose resulted in an increase of sister chromatid exchanges in the cultures lymphocytes.

Thus, in summary of the reported studies using various aluminum compounds, the author stated, that in agreement with their non-carcinogenic activity, aluminum compounds failed to show positive results in most short-term and animal experiments to determine genotoxic potential of aluminum compounds lead to contradictory results with a suggestion of an anti-genotoxic potential.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the attached read-across report (see IUCLID section 13).