Talc (Mg3H2(SiO3)4)

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

There are conclusive but not sufficient data for the classification of substance Talc (Mg3H2(SiO3)4) with regard to mutagenicity/genetic toxicity. It is concluded that the substance Talc (Mg3H2(SiO3)4) does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)

Principles of method if other than guideline:

primary screening by the chromosomal aberration test in vitro

GLP compliance:

not specified

Type of assay:

in vitro mammalian cell transformation assay

Target gene:

rat pleural mesothelial cells (RPMC).

Species / strain / cell type:

mammalian cell line, other: rat pleural mesothelial cells (RPMC)

Details on mammalian cell type (if applicable):

In the SCE assay, RPMC were treated with 0, 2, 5, 10, and 15 μg/cm2 of each talc sample for 48 h.

Additional strain / cell type characteristics:

not specified

Metabolic activation:

without

Test concentrations with justification for top dose:

Two negative reference particle controls, anatase and attapulgite, and the two positive controls reference particles named previously were used, as were the chemical controls mitomycin C in water and K2CrO4 in culture medium.

Vehicle / solvent:

chemical controls mitomycin C in water and K2CrO4 in culture medium.

Untreated negative controls:

yes

Remarks:

untreated cells

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Details on test system and experimental conditions:

In the SCE assay, RPMC were treated with 0, 2, 5, 10, and 15 μg/cm2 of each talc sample for 48 h. Two negative reference particle controls, anatase and attapulgite, and the two positive controls reference particles named previously were used, as were the chemical controls mitomycin C in water and K2CrO4 in culture medium.

Evaluation criteria:

Two negative reference particle controls, anatase and attapulgite, and the two positive controls reference particles named previously were used, as were the chemical controls mitomycin C in water and K2CrO4 in culture medium. T

Statistics:

no data

Species / strain:

mammalian cell line, other: rat pleural mesothelial cells (RPMC)

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

Exposure of rat pleural mesothelioma cells to 3 talc samples and 3 asbestos fibre samples as a positive control (anatase, chrysotile and crocidolite) led to increased sister chromatid exchange and to increased DNA repair synthesis (UDS) only with the asbestos samples, but not with the talc samples

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results: negative

Talc did not cause a statistically significant increase in SCEs and was not clastogenic. The negative particle controls and chemical controls gave expected results; chrysotile and crocidolite statistically significantly increased SCEs in 2/4 and 3/8 experiments, respectively.

Executive summary:

The test substance is non-mutagenic under the given experimental conditions.

Reference 2

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test)

Principles of method if other than guideline:

primary screening by the chromosomal aberration test in vitro

GLP compliance:

not specified

Type of assay:

in vitro mammalian cell transformation assay

Target gene:

rat pleural mesothelial cells (RPMC).

Species / strain / cell type:

mammalian cell line, other: rat pleural mesothelial cells (RPMC)

Details on mammalian cell type (if applicable):

DNA synthesis (UDS) assay or a sister chromatid exchange (SCE) assay in rat pleural mesothelial cells (RPMC).
In the UDS assay, the cells were treated with 0, 10, 20, or 50 μg/cm2 of each sample of talc for 24 h. A negative reference particle controls, anatase, and two positive controls reference particles, Rhodesian chrysotile and crocidolite were used; mean particle sizes of the three talc samples were 0.7, 3.2, and 3.1 μm, respectively. The particles were dispersed in culture medium at a concentration of 560 μg/ml by sonication.

Additional strain / cell type characteristics:

not specified

Metabolic activation:

without

Test concentrations with justification for top dose:

In the UDS assay, the cells were treated with 0, 10, 20, or 50 μg/cm2 of each sample of talc for 24 h. A negative reference particle controls, anatase, and two positive controls reference particles, Rhodesian chrysotile and crocidolite were used; mean particle sizes of the three talc samples were 0.7, 3.2, and 3.1 μm, respectively. The particles were dispersed in culture medium at a concentration of 560 μg/ml by sonication.

Vehicle / solvent:

The particles were dispersed in culture medium at a concentration of 560 μg/ml by sonication.

Untreated negative controls:

yes

Remarks:

untreated cells

Negative solvent / vehicle controls:

yes

True negative controls:

yes

Positive controls:

yes

Details on test system and experimental conditions:

In the UDS assay, the cells were treated with 0, 10, 20, or 50 μg/cm2 of each sample of talc for 24 h. A negative reference particle controls, anatase, and two positive controls reference particles, Rhodesian chrysotile and crocidolite were used; mean particle sizes of the three talc samples were 0.7, 3.2, and 3.1 μm, respectively.

Evaluation criteria:

None of the talc samples enhanced UDS. The negative and positive particles yielded the expected results.

Statistics:

no data

Species / strain:

mammalian cell line, other: rat pleural mesothelial cells (RPMC)

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

Exposure of rat pleural mesothelioma cells to 3 talc samples and 3 asbestos fibre samples as a positive control (anatase, chrysotile and crocidolite) led to increased sister chromatid exchange and to increased DNA repair synthesis (UDS) only with the asbestos samples, but not with the talc samples

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results:negative
Talc was not genotoxic in an unscheduled DNA synthesis (UDS) assay or a sister chromatid exchange (SCE) assay in rat pleural mesothelial cells (RPMC).

Executive summary:

The test substance is non-mutagenic under the given experimental conditions.

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

QSAR prediction:QSAR method for chemicals properties assessment. Relevant for in vitro (Ames test) mutagenicity endpoints.

Qualifier:

according to guideline

Guideline:

other: ToxTree: Benigni/Bossa rules for carcinogenicity and mutagenicity

Principles of method if other than guideline:

This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs). The SAs for mutagenicity are molecular functional groups or substructures known to be linked to the mutagenic activity of chemicals. As one or more SAs embedded in a molecular structure are recognised, the system flags the potential mutagenicity of the chemical. The present list of SAs is a subset of the original Toxtree list, obtained by eliminating the SAs for nongenotoxic carcinogenicity.

GLP compliance:

no

Remarks:

not applicable. QSAR model in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs) relevant for in vitro (Ames test) mutagenicity endpoints.

Type of assay:

other: QSAR model

Target gene:

This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs).

Species / strain / cell type:

S. typhimurium TA 100

Test concentrations with justification for top dose:

QSAR model in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs) relevant for in vitro (Ames test) mutagenicity endpoints.

Untreated negative controls:

other: QSAR model

Negative solvent / vehicle controls:

other: QSAR model

True negative controls:

other: QSAR model

Positive controls:

other: QSAR model

Details on test system and experimental conditions:

This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree.

Evaluation criteria:

This profiler is based on the Mutagenicity/Carcinogenicity module of the software Toxtree. It works as a decision tree for estimating in vitro (Ames test) mutagenicity, based on a list of 30 structural alerts (SAs). The SAs for mutagenicity are molecular functional groups or substructures known to be linked to the mutagenic activity of chemicals. As one or more SAs embedded in a molecular structure are recognised, the system flags the potential mutagenicity of the chemical. The present list of SAs is a subset of the original Toxtree list, obtained by eliminating the SAs for nongenotoxic carcinogenicity.

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

other: QSAR model

Untreated negative controls validity:

other: QSAR model

Additional information on results:

Benigni/Bossa rules for carcinogenicity and mutagenicity:
- Structural Alert for genotoxic carcinogenicity NO
- Potential S. typhiunium TA100 mutagen based on QSAR NO
- Negative for genotoxic carcinogenicity YES

1.6. Profiling results:

DNA binding by OECD

No alert found

Est rogen Receptor Binding

Non binder, non cyclic structure

OECD HPV Chemical Categories

Amorphous silica silicates

Protein binding by OECD

No alert found

Protein binding potency

Not possible to classify according to these rules (GSH)

Superfragments

No superfragment

Toxic hazard classification by Cramer (original)

High (Class III)

US-EPA New Chemical Categories

Not categorized

Conclusions:

Interpretation of results ):negative
No alert found.The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS.
The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS and therefore Talc (Mg3H2(SiO3)4) does not cause in vitro mutagenicity (Ames test)

Executive summary:

The query structure is not recognized among the in vitro mutagenicity (Ames test) alerts by ISS and does not cause in vitro mutagenicity (Ames test).

No mutagenic activity in the (Q)SAR study, In vitro mutagenicity (Ames test) alerts by ISS for  Talc (Mg3H2(SiO3)4) and does not cause in vitro mutagenicity (Ames test) .This QSAR method is Relevant for in vitro (Ames test) mutagenicity endpoints.

Reference 4

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium, other: Salmonella typhimurium TA1530 and G46

Additional strain / cell type characteristics:

not specified

Species / strain / cell type:

Saccharomyces cerevisiae

Details on mammalian cell type (if applicable):

Saccharomyces cerevisiae D3

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Liver microsome fraction (S9) - prepared from the liver of mice

Test concentrations with justification for top dose:

In the host-mediated assay, male ICR mice served as the host and groups of 10 animals were dosed by gavage with a single dose or once daily for 5 days with 30, 300, 3000, or 5000 mg/kg talc. Salmonella typhimurium TA1530 and G46 and Saccharomyces cerevisiae D3 were the indicator organisms. Saline was the negative control and 100 mg/kg dimethyl nitrosamine and intramuscular administration of 350 mg/kg ethyl methane sulfonate were the positive controls. For comparison, a microdrop of solution, 0.01-0.25 ml, of talc was evaluated in an Ames test using S. typhimurium TA1530 and G46 and S. cerevisiae D3.

Vehicle / solvent:

Saline

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

not specified

Details on test system and experimental conditions:

In the host-mediated assay, male ICR mice served as the host and groups of 10 animals were dosed by gavage with a single dose or once daily for 5 days with 30, 300, 3000, or 5000 mg/kg talc. Salmonella typhimurium TA1530 and G46 and Saccharomyces cerevisiae D3 were the indicator organisms. Saline was the negative control and 100 mg/kg dimethyl nitrosamine and intramuscular administration of 350 mg/kg ethyl methane sulfonate were the positive controls. For comparison, a microdrop of solution, 0.01-0.25 ml, of talc was evaluated in an Ames test using S. typhimurium TA1530 and G46 and S. cerevisiae D3.

Evaluation criteria:

Talc was not genotoxic in a host-mediated assay or cytogenetic assay.

Statistics:

not mandatory for the Ames test

Species / strain:

S. typhimurium, other: Salmonella typhimurium TA1530 and G46

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

not examined

Positive controls validity:

not specified

Species / strain:

Saccharomyces cerevisiae

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

not examined

Positive controls validity:

not specified

Additional information on results:

No significant increases in the number of revertant colonies were detected in any S. typhimurium strains at the maximum dose.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

Interpretation of results :negative
The test substance is non-mutagenic under the given experimental conditions.

Executive summary:

Talc caused no significant increase in mutant or recombinant frequencies in the host-mediated assay, and it was not mutagenic in the Ames test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Link to relevant study records

Reference

Endpoint:

in vivo mammalian germ cell study: gene mutation

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)

Principles of method if other than guideline:

rat dominant lethal assay.

GLP compliance:

yes

Type of assay:

rodent dominant lethal assay

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Groups of 10 male Sprague-Dawley rats
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 to 25 °C
- Humidity (%): 40 to 50 %
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Route of administration:

oral: gavage

Vehicle:

no

Details on exposure:

Groups of 10 male rats were dosed by gavage with a single dose or once daily for 5 days with 30, 300, 3000, or 5000 mg/kg talc. Saline was used as the negative controls and 0.1 μg/ml TEM (i.p.) was the positive control.

Duration of treatment / exposure:

once daily for 5 days

Frequency of treatment:

once a day

Dose / conc.:

30 mg/kg bw/day

Dose / conc.:

300 mg/kg bw/day

Dose / conc.:

3 000 mg/kg bw/day

Dose / conc.:

5 000 mg/kg bw/day

No. of animals per sex per dose:

10/male/dose

Control animals:

yes, concurrent vehicle

Positive control(s):

0.1 μg/ml TEM (i.p.) was the positive control.

Tissues and cell types examined:

chromosome aberrations in the bone marrow or no dominant lethal mutations

Evaluation criteria:

Saline was used as the negative controls and 0.1 μg/ml TEM (i.p.) was the positive control.

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other:

Remarks:

There were no dose-response or time trend patterns; talc did not induce dominant lethal mutations in this assay.

Additional information on results:

There were no dose-response or time trend patterns; talc did not induce dominant lethal mutations in this assay.

Conclusions:

Interpretation of results : negative
In rats, no chromosome aberrations in the bone marrow or no dominant lethal mutations were observed after one or five administrations of 30 to 5000 mg talc/kg body weight

Executive summary:

Talc was not genotoxic in a rat dominant lethal assay.

Groups of 10 male rats were dosed by gavage with a single dose or once daily for 5 days with 30, 300, 3000, or 5000 mg/kg talc. Saline was used as the negative controls and 0.1 μg/ml TEM (i.p.) was the positive control.

There were no dose-response or time trend patterns; talc did not induce dominant lethal mutations in this assay.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

In vitro

Talc does not induce mutations in Salmonella typhimurim TA 1530 or his G 46. Gene mutations were not induced in Saccharomyces cerevisiae (D 3) nor were chromosome aberrations found in human WI38 cells (2–200 µg/ml) .

 

Exposure of rat pleural mesothelioma cells to 3 talc samples and 3 asbestos fibre samples as a positive control (anatase, chrysotile and crocidolite) led to increased sister chromatid exchange and to increased DNA repair synthesis (UDS) only with the asbestos samples, but not with the talc samples (Endo-Capron et al. 1993).

 

 

 In vivo

In the host-mediated assay, no mutations were observed in the Salmonella typhimurium strains TA 1530 and his G46 or in Saccharomyces cerevisiae D3 after one or five administrations of 30 to 5000 mg talc/kg body weight to mice.

In rats, no chromosome aberrations in the bone marrow or no dominant lethal mutations were observed after one or five administrations of 30 to 5000 mg talc/kg body weight .

 

Justification for classification or non-classification

Based on the hazard assessment of Talc (Mg3H2(SiO3)4) in section 2.1 and 2.2. in IUCLID 6, available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health” andaccording to the criteria described in Directive 67/548 and in the CLP Regulation:

 

Directive 67/548	Mutagenicity-Genetic Toxicity Muta. Cat. 1; R46 May cause heritable genetic damage. Muta. Cat. 2; R46 May cause heritable genetic damage. Muta. Cat. 3; R68 Possible risk of irreversible effects.
CLP	Germ cell mutagenicity Muta. 1A Muta. 1B Muta. 2 H340: May cause genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>. H341: Suspected of causing genetic defects <state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard>.

 

 

It is concluded that the substance Talc (Mg3H2(SiO3)4) does not meet the criteria to be classified for human health hazards for Mutagenicity-Genetic Toxicity