3-chloropropionic acid

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Weight-of-evidence approach was applied. Data originated from a secondary source on bacterial gene mutation assays. The results are consistently positive in the same strains over the 5 studies (Salmonella TA 100 and TA 1535 and E. coli WP2 uvrA pKM101).

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Test method was similar to OECD guideline 471, but there is no data on positive controls. No data on GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

Remarks:

(No data on positive controls)

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain / cell type:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Metabolic activation system:

Rat, Liver, S9, Sodium phenobarbital and 5,6-benzoflavone (10%)

Test concentrations with justification for top dose:

0, 1.22, 4.88, 19.5, 78.1, 313, 1250, 5000 µg/plate

Vehicle / solvent:

Water

Negative solvent / vehicle controls:

yes

Positive controls:

not specified

Details on test system and experimental conditions:

Method: Preincubation

Species / strain:

S. typhimurium, other: TA 100 and TA 1535

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Positive controls validity:

not specified

Species / strain:

E. coli WP2 uvr A pKM 101

Metabolic activation:

with and without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Positive controls validity:

not specified

Species / strain:

S. typhimurium, other: TA 98 and TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Positive controls validity:

not specified

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Test substance was mutagenic on Salmonella typhimurium TA 100 and TA 1535, and on E. coli WP2 uvrA pKM 101, with and without metabolic activation. It was non-mutagenic on Salmonella typhimurium TA 98 and TA 1537, with and without metabolic activation.

Conclusions:

Interpretation of results (migrated information):
ambiguous

Test substance was mutagenic on Salmonella typhimurium TA 100 and TA 1535, and on E. coli WP2 uvrA pKM 101, with and without metabolic activation. It was non-mutagenic on Salmonella typhimurium TA 98 and TA 1537, with and without metabolic activation.

Executive summary:

3-chloropropanoic acid was tested for mutagenicity in the strains TA 100, TA 1535, TA 1537, and TA 98 of Salmonella typhimurium and in E. coli WP2 uvrA pKM 101. The mutagenicity studies were conducted in the absence and in the presence of a metabolizing system derived from rat liver homogenate. The tested concentrations were: 0, 1.22, 4.88, 19.5, 78.1, 313, 1250, and 5000 µg/plate.

Test substance was mutagenic on Salmonella typhimurium TA 100 and TA 1535, and on E. coli WP2 uvr A pKM 101, with and without metabolic activation. It was non-mutagenic on Salmonella typhimurium TA 98 and TA 1537, with and without metabolic activation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Additional information

Additional information from genetic toxicity in vitro:

Data were obtained from a secondary source on bacterial gene mutation assays (Japan Chemical Industry Ecology-Toxicology & Information Center, JETOC, 2005).

3-chloropropanoic acid was tested for bacterial reverse mutagenicity with the strains TA 98, TA 100, TA1535 and TA 1537 of Salmonella typhimurium and with the strain WP2 uvrA pk101 of E. coli at various concentrations with and without metabolic activation. An overview of the studies, strains and doses is provided in Table 1 below.

Table 1.

Species	S. typhimurium								E. coli
Strain	TA 98	TA 98	TA 100	TA 100	TA 1535	TA 1535	TA 1537	TA 1537	WP2 uvrA pKM 101	WP2 uvrA pKM 101
Metabolic activation	Yes	No	Yes	No	Yes	No	Yes	No	Yes	No
Genetic toxicity in vitro 07.06.01_01 JETOC   All groups: 0, 1.22, 4.88, 19.5, 78.1, 313, 1250, 5000 µg/plate	-	-	+	+	+	+	-	-	+	+
Genetic toxicity in vitro 07.06.01_02 JETOC   All groups: 0, 313, 625, 1250, 2500, 5000 µg/plate	-	-					-		+	+
Genetic toxicity in vitro 07.06.01_03 JETOC Doses: 0, 19.5, 39.1, 78.1, 156, 313 µg/plate			+	+
Genetic toxicity in vitro 07.06.01_04 JETOC TA 1535: 0, 1.22, 2.44, 4.88, 9.77, 19.5, 39.1, and 78.1 µg/plate. TA 1537: 0, 1.22, 2.44, 4.88, 9.77, and 19.5 µg/plate					+	+		-
Genetic toxicity in vitro 07.06.01_05 JETOC All groups: 0, 2.44, 4.88, 9.77, 19.5, 39.1, 78.1, 156, 313, 625,1250, 2500, 5000 µg/plate								-

As demonstrated by the table, the S. typhiumurium strains TA 100 and TA 1535 as well as the E. coli strain WP2 uvrA pk101 tested positive with and without metabolic activation in more than one study (at different dose levels).
The S. typhimurium strains TA 98 and TA 1537 tested negative with and without metabolic activation in more than one study (at different dose levels).

From the data, it can be concluded that 3-chloropropionic acid is positive for bacterial reverse mutagenicity in Salmonella typhimurium TA 100 and TA 1535 and in E. coli WP2 uvrA pKM101 strains, both with and without metabolic activation.

Justification for selection of genetic toxicity endpoint
All endpoints are providing weight-of-evidence on bacterial mutagenicity of 3-chloropropanoic acid, however the first study comprises 5 strains tested up to 5000 µg/plate with and without metabolic activation.

Justification for classification or non-classification

Taking into account the repeated findings in the in vitro mutagenicity as well as the positive in vivo carcinogenicity study, the test substance is classified as "MUTAGENIC" category 2 according to the UN GHS. The test substance is assigned to Packing Group 2 and to EU Risk-Phrase (R68).