Fatty acids tall-oil, reaction products with acrylic acid, potassium salt

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

The substance fatty acids, tall-oil, reaction products with acrylic acid has been assessed for mutagenic activity in three in vitro assays, namely an Ames study, a mouse lymphoma assay and a chromosome aberration study and was found negative in all three studies, each performed with and without metabolic activation. Thus, it is reasonably assumed that the test substance and its corresponding potassium salt are non-mutagenic and further in vivo studies are currently not required to be performed.

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target substance fatty acids, tall-oil, reaction products with acrylic acid potassium salt is the corresponding potassium salt of the source substance fatty acids, tall-oil, reaction products with acrylic acid and manufactured accordingly by neutralisation with potassium hydroxide. As the potassium salt does not contribute to the genetic toxicity because it is an essential nutrient, a read-across to the free acids is justified.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance actually is manufactured form the source substance by neutralisation of fatty acids, tall-oil, reaction products with acrylic acid (source substance) with potassium hydroxide, forming the target substance fatty acids, tall-oil, reaction products with acrylic acids potassium salt. The source substance has been registered already and a test according to OECD guideline 471 (Ames test) has shown that, Diacid 1550 did not show any mutagenic activity in the Salmonella Typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 with and without activation under the conditions of the test.
3. ANALOGUE APPROACH JUSTIFICATION
The structure of the organic moiety of source and target substance is identical and thus, read-across form the free acid to its salt is common practice and justified.
4. DATA MATRIX
Not relevant here as organic moieties of source and target substance are identical, and both only do differ by the cation potassium present in the target substance (compared to a proton in the source substance).

Reason / purpose for cross-reference:

read-across source

Species / strain:

other: S.typhimurium TA 1537, TA 1535, TA 98, TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not determined

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Conclusions:

In this Ames test, Diacid 1550 did not show any mutagenic activity in the Salmonella Typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 with and without activitation under the conditions of this test. Accordingly, also the corresponding potassium salt (fatty acids, tall-oil, reaction products with acrylic acid, potassium salt) is rated as non-mutagenic for the strains tested.

Reference 2

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target substance fatty acids, tall-oil, reaction products with acrylic acid potassium salt is the corresponding potassium salt of the source substance fatty acids, tall-oil, reaction products with acrylic acid and manufactured accordingly by neutralisation with potassium hydroxide. As the potassium salt does not contribute to the genetic toxicity because it is an essential nutrient, a read-across to the free acids is justified.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance actually is manufactured form the source substance by neutralisation of fatty acids, tall-oil, reaction products with acrylic acid (source substance) with potassium hydroxide, forming the target substance fatty acids, tall-oil, reaction products with acrylic acids potassium salt. The source substance has been registered already and a test according to OECD guideline 473 (in vitro Chromosome Aberration assay) has shown, that Diacid 1550 did not cause a significant increase in the number of cells with aberrations or a positive dose response trend for concentrations of 6.3 to 100 µg/mL in Chinese Hamster Ovary Cells with and without metabolic activation under the conditions of the test.
3. ANALOGUE APPROACH JUSTIFICATION
The structure of the organic moiety of source and target substance is identical and thus read-across form the free acid to its salt is common practice and justified.
4. DATA MATRIX
Not relevant here as organic moieties of source and target substance are identical, and both only do differ by the potassium cation present in the target substance (compared to a proton in the source substance).

Reason / purpose for cross-reference:

read-across source

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity nor precipitates, but tested up to recommended limit concentrations

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: all strains/cell types tested

Conclusions:

In an in vitro Chromosome Aberration assay, Diacid 1550, the corresponding free acid to the potassium salt, did not cause a significant increase in the number of cells with aberrations or a positive dose response trend for concentrations of 6.3 to 100 µg/mL in Chinese Hamster Ovary Cells with and without metabolic activitation under the conditions of this test. Thus, the test substance fatty acids, tall-oil, reaction product with acrylic acid was found negative, with and without metabolic activation, in this in vitro chromosome aberration assay, and this finding is applicable to the corresponding potassium salt too.

Reference 3

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The target substance fatty acids, tall-oil, reaction products with acrylic acid potassium salt is the corresponding potassium salt of the source substance fatty acids, tall-oil, reaction products with acrylic acid and manufactured accordingly by neutralisation with potassium hydroxide. As the potassium salt does not contribute to the genetic toxicity because it is an essential nutrient, a read-across to the free acids is justified.
2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target substance actually is manufactured form the source substance by neutralisation of fatty acids, tall-oil, reaction products with acrylic acid (source substance) with potassium hydroxide, forming the target substance fatty acids, tall-oil, reaction products with acrylic acids potassium salt. The source substance has been registered already and a test according to OECD guideline 476 the test item did not induce any toxicologically significant increases in the mutant frequency at the TK +/- locus in L5178Y cells and is therefore considered to be non-mutagenic under the conditions of the test.
3. ANALOGUE APPROACH JUSTIFICATION
The structure of the organic moiety of source and target substance is identical and thus, read-across form the free acid to its salt is common practice and justified.
4. DATA MATRIX
Not relevant here as organic moieties of source and target substance are identical, and both only do differ by the cation potassium present in the target substance (compared to a proton in the source substance).

Reason / purpose for cross-reference:

read-across source

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

not applicable

Positive controls validity:

valid

Remarks on result:

other: strain/cell type: Thymidine kinase, TK +/-, locus of the L5178Y mouse lymphoma cell line.

Conclusions:

The test item fatty acids, tall-oil, reaction products with acrylic acid did not induce any toxicologically significant increases in the mutant frequency at the TK +/- locus in L5178Y cells and therefore, is considered to be non-mutagenic under the conditions of the test. Accordingly, also the corresponding potassium salt is reasonably assumed to be non-mutagenic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the negative results from three in vitro assays, namely an Ames study, a mouse lymphoma assay and a chromosome aberration study, each performed with and without metabolic activation it is concluded that the substance in non-mutagenic and hence, not subject to classification for mutagenicity according to CLP (Regulation EC No. 127272008).