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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

IN VITRO GENETIC TOXICITY

Five Ames Test + one E.Coli DNA-Lethality

- NTP (eq. to OECD 471, 1999, K, rel. 2): not mutagenic with and without metabolic activation in S. typhimurium TA97 - TA98 - TA100 - TA102 - TA104 - TA1535

- May (OECD 471, 1989, GLP, SS, rel. 2): not mutagenic/ devoid of mutagenic activity under the conditions of the test with and without metabolic activation in S. typhimurium TA98, TA1538, TA100, TA1535 and TA1537

- Hossack (No guideline followed/publication, 1978, rel.3): not mutagenic/ failed to produce any clear evidence of mutagenic potential with and without metabolic activation in S. thyphimurium strains TA1537, TA98 & TA100

- Gocke (No guideline followed/publication, 1981, rel.4): mutagenic with and without metabolic activation in S. thyphimurium strains TA1535a, TA1535b, TA1538, TA1537, TA98 & TA100

- May (No guideline followed, 1989, rel.2): Clear positive responses were observed in WP67 and CM871 strains treated with the positive control in absence of S9. Sodium chlorate induced responses suggestive of DNA damage in E.coli strain WP67 and CM871

- Eckhardt (Publication/ Abstract only with limited information, 1982, rel.4): mutagenic activity in the Ames test on TA1535 + S9.

Two Mammalian Cell Gene Mutation Assays

- Clarke (OECD 476, 2007, HGPRT/CHO, GLP, K, rel. 1): not mutagenic up to cytotoxic concentrations with and without metabolic activation

- Hodson-Walker (comparable to OECD 476, 1989, HGPRT/CHO, GLP, K, rel. 1): not mutagenic up to cytotoxic concentrations with and without metabolic activation

One DNA damage and repair study

- Seeberg (OECD 482, GLP, K, rel. 1): not induce unscheduled DNA synthesis in HeLa S3 cells, either in the absence or presence of S9 metabolic activation, under the reported experimental conditions.

IN VIVO GENETIC TOXICITY

Four Micronucleus studies

- Mackay (OECD 474, 1989, GLP, K, rel. 1): no evidence of induced chromosomal or other damage leading to micronucleus formation in polychromatic erythrocytes of treated mice 24, 48 or 72 hours after oral administration of sodium chlorate

- NTP (eq. to OECD 474, 1999, SS, rel. 3): no increases in the frequencies of micronucleated NCEs were seen in peripheral blood samples from male and female B6C3F1 mice exposed to concentrations of 125 to 2,000 mg/L sodium chlorate in drinking water for 3 weeks.

- Meier (No guideline followed/publication, 1985, rel.3): Negative

- Gocke (No guideline followed/publication, 1981, rel.4): Negative

A Chromosome aberration test

Meier (No guideline followed/publication, 1985, rel.3): Negative

A chromosomal damage and sperm-head abnormalities in mice

Meier (No guideline followed/publication, 1985, rel.3): Negative

A Drosophila T34-12 Basic test

(Gocke, 1981, rel.4) : Positive

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Table 7.6/1: Summary of in vitro genotoxicity tests

 

Test n°

Test / Guideline

Reliability

Focus

Strains tested

Metabolic activation

Test concentration

Statement

1

NTP

Ames Test

(eq. to OECD 471)

K, rel. 2, 1999

Bacterial gene mutation

TA97,TA98 TA100, TA102, TA104, TA1535

-S9

+S9

100 to 10,000 µg/plate

-S9 : non mutagenic

+S9 : non mutagenic

2

May

Ames Test

(OECD 471, 1989, GLP, SS, rel. 2)

Bacterial gene mutation

TA98, TA1538, TA100,TA1535 and TA1537

-S9

+S9

Up to 5000 micrograms/plate

-S9 : not mutagenic

+S9 : not mutagenic

 3

Hossack

Ames Test

(No guideline followed/

publication, 1978, rel.3)

Bacterial gene

mutation

TA1537, TA98 & TA100

 -S9

+S9

10, 100, 1000,

10000 µg/plate

-S9 : non mutagenic

+S9 : non mutagenic

 4

Gocke

Ames Test

(No guideline

followed/

publication,

1981, rel.4

Bacterial gene

mutation

TA1535a,

TA1535b, TA1538, TA1537, TA98 & TA100

-S9

+S9

  Up to 3600

microgram/plate

-S9 : mutagenic

+S9 : mutagenic

The frequency of revertants

in strains TA1535 A and B

was approximately doubled on VB medium at a dose of 12 µmol/plate

 5

May

E.Coli-DNA-Lethality

(No guideline followed,

1989, rel.2)

 Gene

mutation

E.coli strain WP2

WP67 and CM871

-S9

+S9 : not

validated

10, 316, 1000,

3160 and 10000 µg/ml

-S9 : responses suggestive

of DNA damage in E.coli strain WP67 and CM871

+S9 : not validated

 6

Eckhardt

Publication/

Abstract only with

limited information,

1982, rel.4

Ames test

Micronucleus test on mouse bone marrow

Recessive-lethal test on Drosophila

 Not specified

 -S9

+S9

 Not specified

Ames test : Positive on TA1535 with

metabolic activation

Drosophila test system: Positive

Micronucleus test: Negative

 7

Clarke

HGPRT/CHO

(OECD 476, 2007,

GLP, K, rel. 1)

 Mammalian gene mutation

Chinese

Hamster ovary

cells

 -S9

+S9

 10, 33, 100, 333, 1000, and 5000 µg/mL

-S9 : non mutagenic

+S9 : non mutagenic

 8

Hodson-Walker

HGPRT/CHO

(comparable to OECD 476, 1989, GLP, K, rel.1)

  Mammalian gene mutation

Chinese

Hamster lungs fibroblasts

cells (V79)

 -S9

+S9

 8, 40, 200, 1000 and 5000 µg/ml

-S9 : non mutagenic

+S9 : non mutagenic

 9

Seeberg

 DNA damage and/or

repair study

(OECD 482, GLP, K, rel. 1)

UDS 

 HeLa S3 cells

-S9

+S9

 100, 316, 1000, 3160 and 10000 µg/ml

-S9 : non mutagenic

+S9 : non mutagenic

 

Table 7.6/1: Summary of in vivo genotoxicity tests

 

Test n°

Test / Guideline

Reliability

Focus

Strains tested

Metabolic activation

Test concentration

Statement

1

Mackay

Micronucleus assay

(OECD 474,1989, GLP, K, rel. 1)

 Chromosomal aberration

 Bone marrow erythrocytes cells

NA

200, 1000 or 5000 mg/kg

 Not clastogenic

2

NTP

Micronucleus assay

(eq. to OECD 474, 1999,

SS, rel. 3)

Chromosomal aberration

 Bone marrow cells

NA

125 to 2,000 mg/L

Not clastogenic

 3

Gocke

 Micronucleus assay

(No guideline followed/

publication, 1981, rel.4)

Chromosomal

aberration

 Bone marrow cells

 NA

530, 1060 and 2120 mg/kg ip

and 2128, 3192 and

4265 mg/kg oral

Not clastogenic

 4

Meier

 Micronucleus assay

(No guideline followed/

publication, 1985, rel.3)

 Chromosomal

aberration

Bone marrow cells

NA

200, 500, 1000 mg/L (6.67, 16.67

and 33.33  mg/kg bw)

 Not clastogenic

 5

Meier

Chromosome abberation

(No guideline followed/

publication, 1985, rel.3)

 Chromosomal

aberration

Human

lymphocytes

-S9

+S9

 200, 500, 1000 mg/L (6.67, 16.67

and 33.33  mg/kg bw)

 -S9 : not

clastogenic

+S9 : not

clastogenic

 6

Meier

Sex-linked recessive lethal test

(No guideline followed/

publication, 1981, rel.4)

 Chromosomal

aberration

Drosophila

Melanogaster

NA

 Not specified

Positive

Sodium chlorate was not mutagenic in the majority of in vitro studies and in all in vivo systems tested. Sodium chlorate did not induce gene mutations in either bacteria or mammalian cells but the results in E.coli are suggestive of a primary DNA damage with no requirement for metabolic activation. This effect was not confirmed in mammalian HeLa S3 cells in vitro where there was no evidence of unscheduled DNA synthesis. Mechanisms of DNA reparation in bacteria being different from those in mammals, the results observed in mammals are considered more relevant for risk assessment.

In the absence of in vivo genotoxicity in somatic, it was therefore concluded that limited evidence of genotoxicity in vitro in bacteria was not relevant to the in vivo situation.

Therefore, based on both in vitro and in vivo studies, there are sufficient reliable data indicating that sodium chlorate has no genotoxic potential.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification for human health according to the Regulation (EC) No. 1272/2008.

 

Self classification:

Based on the available data, no additional classification is proposed regarding genetic toxicity according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.