Manganese, 4-[(5-chloro-4-methyl-2-sulfophenyl)azo]-3-hydroxy-2-naphthalenecarboxylic acid complex

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Pigment Red 48:4(Mn) is not genotoxic in vitro based on experimental data with Pigment Red 48:4(Mn) and pigments of the same category.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

Please see the category read-across justification in the category object.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Reference 2

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

Please see the category read-across justification in the category object.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Species / strain:

Chinese hamster lung (CHL/IU)

Metabolic activation:

with and without

Genotoxicity:

other: clastogenicity negative

Cytotoxicity / choice of top concentrations:

not specified

Species / strain:

Chinese hamster lung (CHL/IU)

Metabolic activation:

with and without

Genotoxicity:

other: polyploidy positive at precipitation

Cytotoxicity / choice of top concentrations:

not specified

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

Please see the category read-across justification in the category object.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Species / strain:

Chinese hamster lung fibroblasts (V79)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Pigment Red 48:4(Mn) was not mutagenic in an Ames test using four tester strains (Bastelle 1979). Tested doses were up to 2 mg/plate and were clearly in the precipitating range and the incubation was performed both with and without metabolic activation. No mutagenic properties were observed. This is consistent with secondary information on an Ames test mentioned in a summary report on colorants (ETAD 1988).

No other data on Pigment Red 48:4(Mn) was available. Detailed experimental data is available for the analogue calcium salt Pigment Red 48:2(Ca), which is also of low solubility.

The mutagenicity of Pigment Red 48:2(Ca) in vitro was assessed in two tests applying both the standard assay with rat liver homogenate and the modified assay for azo compounds (Prival-assay). Tested samples were commercial products containing varying amounts of additives. With the limitation in the number of tester strains, the non-key study is reliable and valid in regard to design, positive and negative control and concentrations. The key study was performed following the latest OECD testing guideline (OECD 471, adopted July 12, 1997) and the principles of GLP and included the Prival assay modification to take into account reductive metabolism of the azo bond.

In vitro mutagenicity in mammalian cells

Mutagenicity in mammalian cells in vitro was investigated of Pigment Red 48:2(Ca) in a HPRT test following OECD testing guideline 476 (adopted July 21, 1997) and the principles of GLP. The test was performed with a sample synthesized without additives and a purity of 99.4%. No indication of a mutagenic effect was observed at concentrations up to 720mg/plate, at least the two highest concentrations being in the precipitating range. This is consistent with the absence of unscheduled DNA synthesis as tested with both with human fibroblasts (Puri 1985) and with primary hepatocytes prepared from arochlor1254-induced rats (Puri 1985). The latter studies were performed under GLP and in combination fulfil the requirements of OECD testing guideline 482 (adopted October 23, 1986). For the DNA-repair assays, concentrations were in similar range and also resulted in precipitation. Higher concentrations were too toxic for scoring. For these two studies, commercial samples with adequately high pigment content were tested.

In vitro clastogenicity in mammalian cells

Clastogenicity of Pigment Red 48:2(Ca) in mammalian cells was investigated in a guideline (OECD 473. adopted July 21, 1997) and GLP compliant study (Höpker 2007). The test was performed with a sample synthesized without additives and a purity of 99.4%. The highest evaluable concentrations were chosen based on visual observation of precipitates. No indication of clastogenicity or polyploidy were observed in either study.

For data on manganese, it is referred to the SCOEL justification document (2011), the Toxicological profile for manganese from the Agency for Toxic Substances and Disease Registry (2012), and the disseminated dossier of manganese dichloride. Overall it can be concluded that manganese is not genotoxic.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for genetic toxicity according to Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008.