Metam-sodium

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Metam Sodium (137-42-8) was evaluated for its mutagenic potential in Salmonella typhimurium TA92, TA98, TA100, TA1535, TA1537 and TA1538 by Standard plate test. The test result was considered to be negative in the presence and absence of metabolic activation.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source.

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

To evaluate the genetic toxicity of Metam Sodium in Salmonella typhimurium TA92, TA98, TA100, TA1535, TA1537, TA1538 by Standard plate test.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name of test material : Metam-sodium
- Molecular formula : C2H4NNaS2
- Molecular weight : 129.1826 g/mol
- Smiles notation : C(=S)(NC)[S-].[Na+]
- InChl : 1S/C2H5NS2.Na/c1-3-2(4)5;/h1H3,(H2,3,4,5);/q;+1/p-1
- Substance type: Organic
- Physical state: Solid

Target gene:

Histidine

Species / strain / cell type:

S. typhimurium, other: TA92, TA98, TA100, TA1535, TA1537, TA1538

Details on mammalian cell type (if applicable):

Not applicable.

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 metabolic activation

Test concentrations with justification for top dose:

20–5000 µg/plate

Vehicle / solvent:

not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

not specified

True negative controls:

not specified

Positive controls:

not specified

Details on test system and experimental conditions:

Details on test system and conditions
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
Exposure duration: 48 hours

NUMBER OF REPLICATIONS: Duplicate

Other: Triplicate plates per test were used.

Rationale for test conditions:

not specified

Evaluation criteria:

Evaluation was done considering a dose dependent increase in the number of revertants /plate.

Statistics:

not specified

Species / strain:

S. typhimurium, other: TA92, TA98, TA100, TA1535, TA1537, TA1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: No mutagenic effect were observed.

Conclusions:

Metam Sodium (137-42-8) was evaluated for its mutagenic potential in Salmonella typhimurium TA92, TA98, TA100, TA1535, TA1537 and TA1538 by Standard plate test. The test result was considered to be negative in the presence and absence of metabolic activation.

Executive summary:

Genetic toxicity study for Metam Sodium was assessed for its mutagenic potential. For this purpose Salmonella typhimurium Reverse Mutation Assay was performed according to OECD Guideline 471. The test substance was exposed to Salmonella typhimurium TA92, TA98, TA100, TA1535, TA1537 and TA1538 by Standard plate test at the concentration of 20–5000 µg/plate. The test substance was exposed for 48 hour in the presence and absence of metabolic activation. No mutagenic effects were observed. Therefore Metam Sodium was considered to be non mutagenic for Salmonella typhimurium TA92, TA98, TA100, TA1535, TA1537 and TA1538 by Standard plate test. Hence the substance cannot be classified as gene mutant in vitro.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

Metam Sodium(137-42-8)was tested for possible clastogenicity in Chinese hamsters using the bone marrow chromosome analysis method. The test result was considered to be negative as there is no increase in the number of aberrant metaphases.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from secondary source.

Qualifier:

according to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Principles of method if other than guideline:

To evaluate possible clastogenicity of Metam Sodium in Chinese hamsters using the bone marrow chromosome analysis method.

GLP compliance:

not specified

Type of assay:

other: In vivo Mammalian Bone Marrow Cytogenetic Test – Chromosomal Analysis"

Specific details on test material used for the study:

- Name of test material : Metam-sodium
- Molecular formula : C2H4NNaS2
- Molecular weight : 129.1826 g/mol
- Smiles notation : C(=S)(NC)[S-].[Na+]
- InChl : 1S/C2H5NS2.Na/c1-3-2(4)5;/h1H3,(H2,3,4,5);/q;+1/p-1
- Substance type: Organic
- Physical state: Solid

Species:

hamster, Chinese

Strain:

other: SH (chin) Ki

Sex:

male/female

Details on test animals or test system and environmental conditions:

Not specified

Route of administration:

oral: gavage

Vehicle:

Not specified

Details on exposure:

Not specified

Duration of treatment / exposure:

2 days

Frequency of treatment:

Single

Post exposure period:

Not specified

Remarks:

0, 150, 300 and 600 mg/kg bw

No. of animals per sex per dose:

5/sex/group

Control animals:

yes, concurrent vehicle

Positive control(s):

Cyclophosphamide
- Route of administration: Oral gavage
- Doses / concentrations: 40 mg/kg

Tissues and cell types examined:

bone marrow

Details of tissue and slide preparation:

Details of tissue and slide preparation
The animals were sacrificed and the bone marrow of the two femora was prepared 6, 24 and48 hours after administration of the highest dose and 24 hours after treatment of the other groups.

Evaluation criteria:

1000 metaphase cells (100/hamster) were scored for each dose level.

Statistics:

Not specified.

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

valid

Remarks on result:

other: No mutagenic effect were observed

Conclusions:

Metam Sodium (137-42-8)was tested for possible clastogenicity in Chinese hamsters using the bone marrow chromosome analysis method. The test result was considered to be negative as there is no increase in the number of aberrant metaphases.

Executive summary:

In Vivo Genetic toxicity study of Metam Sodium was assessed for its possible clastogenic effect. For this purpose In vivo Mammalian Bone Marrow Cytogenetic Test – Chromosomal Analysis" was performed  according to OECD Guideline 475. The test substance was exposed to Chinese hamsters using the bone marrow chromosome analysis method. The test substance was tested in Chinese hamsters at the concentration of 0, 150, 300 and 600 mg/kg bw. The animals were sacrificed and the bone marrow of the two femora was

prepared 6, 24 and48 hours after administration of the highest dose and 24 hours after treatment of the other groups. Single oral administration of Metam Sodium in doses of 150,

300 and 600 mg/kg bw did not lead to any increase in the number of aberrant metaphases. There were no significant differences in the types and frequency of aberrations between the dose groups and the solvent control group. Therefore Metam Sodium was considered to be non mutagenic inChinese hamsters bone marrow chromosome analysis. Hence the substance cannot be classified as Gene mutant in vitro.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Genetic toxicity In-vitro;

Various experimental studies were reviewed to determine the mutagenic nature of target substance Metam-sodium (137-42-8) . The studies are as mentioned below:

Gene mutation toxicity study was observed by European Commission (European Chemicals Bureau, 2000) to determine the mutagenic nature of target substance Metam-sodium (137-42-8 ) using Salmonella typhimurium strains. Genetic toxicity study for Metam Sodium was assessed for its mutagenic potential. For this purpose Salmonella typhimurium Reverse Mutation Assay was performed according to OECD Guideline 471. The test substance was exposed to Salmonella typhimurium TA92, TA98, TA100, TA1535, TA1537 and TA1538 by Standard plate test at the concentration of 20–5000 µg/plate. The test substance was exposed for 48 hour in the presence and absence of metabolic activation. No mutagenic effects were observed. Therefore Metam Sodium was considered to be non mutagenic for Salmonella typhimurium TA92, TA98, TA100, TA1535, TA1537 and TA1538 by Standard plate test. Hence the substance cannot be classified as gene mutant in vitro.

Supported by an experimental study observed by European Commission (European Chemicals Bureau, 2000) to determine the mutagenic nature of target substance Metam-sodium (137-42-8 ) using Salmonella typhimurium strains. Genetic toxicity study for Metam Sodium was assessed for its mutagenic potential. For this purpose Salmonella typhimurium Reverse Mutation Assay was performed according to OECD Guideline 471. The test substance was exposed to Salmonella typhimurium TA92, TA98, TA100, TA1535, TA1537 and TA1538 by Preincubation test at the concentration of 4–5000 µg/plate. The test substance was exposed for 48 hour in the presence and absence of metabolic activation. No mutagenic effects were observed. Therefore Metam Sodium was considered to be non mutagenic for Salmonella typhimurium TA92, TA98, TA100, TA1535, TA1537 and TA1538 by Preincubation test. Hence the substance cannot be classified as gene mutant in vitro.

It is further supported by another experimental study observed European Commission (European Chemicals Bureau, 2000) to determine the mutagenic nature of target substance Metam-sodium (137-42-8) using mammalian cells. Genetic toxicity study for Metam Sodium was assessed for its mutagenic potential. For this purpose Chinese Hamster Ovary Cells by HGPRT assay was performed according to OECD Guideline 476.Chinese hamster CHO-K1 cells were exposed to 0, 0.0000464, 0.0001, 0.000215, 0.000464, 0.001, 0.00215, 0.00464 and 0.01 mg/ml of the test substance for 4 hours with and without metabolic activation in an HGPRT forward mutation assay. No mutagenic effects were observed. Therefore Metam Sodium was considered to be non mutagenic for Chinese Hamster Ovary Cells by HGPRT assay. Hence the substance cannot be classified as gene mutant in vitro.

Another study observed European Commission (European Chemicals Bureau, 2000) to determine the mutagenic nature of target substance Metam-sodium (137-42-8) using Cytogenetic Assay. Genetic toxicity study for Metam Sodium was assessed for its mutagenic potential. For this purpose Cytogenetic Assay was performed according to OECD Guideline 473. The test substance was exposed to human lymphocytes by Cytogenetic Assay at the concentration of0, 10 and 40µg/ml without S–9 mix for 24 hour, while 0, 10, 20 or 40µg/ml with S–9 for 2 hours. Significant Chromosome aberrations were observed in metaphase cells. Therefore Metam Sodium was considered to be mutagenic for human lymphocytes by Cytogenetic Assay. Hence the substance can be classified as gene mutant in vitro.

Based on the majority of experimental data and applying weight of evidence for the target chemical Metam-sodium (137-42-8) does not induce gene mutation in vitro. Hence the test chemical is not likely to classify as a gene mutant in vitro.

Genetic toxicity In-vivo;

Experimental study was reviewed to determine the mutagenic nature of target substance Metam-sodium (137-42-8). The studies are as mentioned below:

Gene mutation toxicity study was observed by European Commission (European Chemicals Bureau, 2000) to determine the mutagenic nature of target substance Metam-sodium (137-42-8 ) using mammalian cells. In Vivo Genetic toxicity study of Metam Sodium was assessed for its possible clastogenic effect. For this purpose In vivo Mammalian Bone Marrow Cytogenetic Test – Chromosomal Analysis" was performed according to OECD Guideline 475. The test substance was exposed to Chinese hamsters using the bone marrow chromosome analysis method. The test substance was tested in Chinese hamsters at the concentration of 0, 150, 300 and 600 mg/kg bw. The animals were sacrificed and the bone marrow of the two femora was prepared 6, 24 and48 hours after administration of the highest dose and 24 hours after treatment of the other groups. Single oral administration of Metam Sodium in doses of 150, 300 and 600 mg/kg bw did not lead to any increase in the number of aberrant metaphases. There were no significant differences in the types and frequency of aberrations between the dose groups and the solvent control group. Therefore Metam Sodium was considered to be non mutagenic inChinese hamsters bone marrow chromosome analysis. Hence the substance cannot be classified as Gene mutant in vitro.

Based on the experimental data for the target chemical ,Metam-sodium (137-42-8) does not induce gene mutation in vivo. Hence the test chemical is not likely to classify as a gene mutant in vivo.

Justification for classification or non-classification

Based on the above annotation and CLP criteria for the target chemical, Metam-sodium (137-42-8) does not induce gene mutation in vitro as well as In vivo. Hence the test chemical is not likely to classify as a gene mutant in vitro and vivo.