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Additional information

No experimental data on sodium acrylate are available. Data on the structural analogue acrylic acid which has been extensively studied in both in vitro and in vivo tests, are included for assessment.

 

 

In vitro gene mutation assays in bacteria

 

Acrylic acid was negative in several Ames assays with and without metabolic activation. Concentrations between 3.15 and 1000 nL/plate were tested in Salmonella typhimurium tester strains TA98, TA100, TA1535 and TA1537 in the absence and presence of S-9 mix. No bacteriotoxic effect was observed up to the highest concentration tested (BASF AG, 1977). In the same 4 Salmonella typhimurium tester strains at concentrations up to 3333 µg/plate was no increase in the mutant frequency caused by the compound. Only at the highest concentration tested a bacteriotoxic effect was found (Zeiger et al., 1987). A bacterial mutation test with Salmonella typhimurium tester strains TA98, TA100, TA1535 and TA1537 was negative in concentrations up to 5000 µg/plate with and without S-9 mix. Doses from 1000 or 3333 µg/plate upwards induced bacteriotoxic effects, depending on the strain (Cameron et al., 1991).

 

 

In vitro tests in mammalian cells

 

A mammalian cell gene mutation test with CHO cells (HGPRT locus) was negative at doses up to 1.9 µL/mL (2000 µg/mL) without S-9 mix and up to 2.4 µL/mL (2500 µg/mL) with S-9 mix. Survival at the highest concentrations was 35% and 24%, respectively (BAMM, 1988, McCarthy et al., 1992).

 

In the mouse lymphoma assay increases of mutation frequencies were found in two independent investigations. Cameron et al. (1991) reported a positive mouse lymphoma assay with and without metabolic activation: without S-9 mix 3-fold to 6-fold dose-related increases of mutant frequencies were induced in the dose range 2.65 to 4.56 mmol/L (191 to 329 µg/mL); with S-9 mix 3-fold to 6-fold increases were found in the dose range 16.2 to 22.1 mmol/L (1167 to 1593 µg/mL). The relative total growth at the concentrations that gave a positive response in the absence of S-9 was 36 -15 % and in the presence of S-9 was 55.5 - 20 %, respectively. At concentrations which resulted in a relative total growth greater than 55 %, no increases in mutant frequencies were observed. The colony size distribution was not determined in this study.

Acrylic acid was mutagenic without exogenous activation in another mouse lymphoma assay comprising of two separate experiments (Moore et al., 1988). A 500 μg/mL concentration of acrylic acid induced a mutant frequency over background of 245 and 325/106 survivors (background = 61 and 80 mutants/106 survivors, respectively) in these two experiments. Induced mutant frequencies above 450/106 survivors were observed at the 550 and 600 μg/mL concentrations; however, the survival was below 10%. The majority of the TFT-resistant colonies was small indicating a clastogenic effect. The maximum induced large-colony mutant frequency was 26/106 survivors (background = 22/106 survivors) and was observed at both the 300 and 500 μg/mL concentrations (colony sizing was performed for selected concentrations in one experiment).

 

Positive effects were described also for in vitro chromosomal aberration assays. Celanese Corp. (1986) reported a positive chromosomal aberration assay in CHO cells with and without metabolic activation. Without S-9 mix, doses of 3.8 and 5.0 µL/mL (approx. 3960 and 5250 µg/mL) induced 11 % and 30 % aberrant cells (2 % in the vehicle control); with S-9 mix, in the dose range 1.6 to 2.8 µL/mL (1700 to 2990 µg/mL) aberration frequencies of 9 % to 28 % were found in a dose-related manner (1 % in the vehicle control). The positive response was not bound exclusively to cytotoxic effects (42 % - 62 % in the absence and 35 % - 68 % relative cloning efficiency in the presence of metabolic activation, respectively) or to decreases in pH (pH was adjusted to pH 7.0) (Celanese Corp. 1986; McCarthy et al., 1992).

More recent studies have indicated that there is an association between chromosomal aberrations and cytotoxicity at exposure concentrations which reduce cell growth to less than 50% of the control value (Galloway, 2000 and references cited therein). These data suggest that the increase in mutagenicity reported in the mouse lymphoma TK and chromosomal aberration assays with acrylic acid may be an artifact of the experimental method. However, at a concentration of 1.6 µL/mL (approx. 1700 µg/mL) in the presence of metabolic activation a significantly elevated frequency of cells with aberrations (9 % versus 1 % in the solvent control) and 68 % survival were reported. Thus, acrylic acid showed clastogenic potential in in vitro assays in mammalian cells.

 

In primary rat hepatocytes acrylic acid did not induce unscheduled DNA synthesis (UDS) in non-toxic doses up to 0.4 µL/mL (420 µg/mL). Higher doses could not be analysed due to high cytotoxicity (BAMM, 1988; McCarthy et al., 1992).

 

 

In vivo Studies

 

Two in vivo bone marrow chromosomal aberration assays with rats gave negative results (Celanese Corp., 1986; McCarthy et al., 1992). Chromosome aberrations were analyzed (5 animals per sex, 50 metaphases per animal) at 6, 12, and 24 h after oral doses of 100, 333 or 1000 mg/kg bw or after exposure to 2000 or 5000 ppm acrylic acid in drinking water (corresponding to approx. 180 and 450 mg/kg bw) for 5 days. In the acute as well as in the subacute regimens the highest doses led to reduced body weight gains. Mitotic activity of bone marrow cells was not influenced by the treatments.

Two dominant lethal assays in CD-1 mice led to negative results. Male mice were given single oral doses (gavage) up to 324 mg/kg bw or five daily oral doses up to 162 mg/kg bw. Immediately after dose administration male mice were mated. Females were checked for vaginal plugs each morning. Each mated female was replaced with a virgin female. The mating process was continued for 46 days. An analysis of the uterine contents of female mice was made 12-15 days after observation of the vaginal plug (McCarthy et al., 1992). Acrylic acid did not induce a statistically significant increase in dead implants accompanied by a significant reduction in live implants at the same dose and time point in either the acute or repeated dosing studies. Likewise, the percentage of dominant lethals was not markedly increased in any treatment group. In contrast, the positive control cyclophosphamide induced an increase in the percentage of dead implants and dominant lethals in both the acute and repeated dosing regimens. Consequently, acrylic acid did not induce a dominant lethal effect.

 

 

Conclusion

 

Acrylic acid did not induce gene mutations in Salmonella typhimurium or CHO cells (HGPRT locus) but was positive in the mouse lymphoma assay and in the in vitro chromosomal aberration test. Since in the mouse lymphoma assay small colonies were induced preferentially, the mutagenic potential of acrylic acid seems to be limited to clastogenicity. In vivo, acrylic acid did not induce mutagenic effects in either rat bone marrow cells or mouse germ cells after oral administration. Based on the present results, it is unlikely that acrylic acid is mutagenic in vivo.

 

Based on the structural similarities between acrylic acid and sodium acrylate, it can be concluded that sodium acrylate is not mutagenic in vivo.

Galloway SM (2000). Environmental and Molecular Mutagenesis 35:191-201


Short description of key information:
No experimental data on sodium acrylate are available. Data on the structural analogue acrylic acid which has been extensively studied, are included for assessment.
Acrylic acid did not induce gene mutations in Salmonella typhimurium or CHO cells (HGPRT locus) but was positive in the mouse lymphoma assay and in the in vitro chromosomal aberration test. Since in the mouse lymphoma assay preferentially small colonies were induced, the mutagenic potential of acrylic acid seems to be limited to clastogenicity. In vivo, acrylic acid did not induce mutagenic effects in either rat bone marrow cells or mouse germ cells after oral administration.
Based on the present results, it is unlikely that sodium acrylate is mutagenic in vivo.

Endpoint Conclusion:

Justification for classification or non-classification

EU classification according to Annex VI of Directive 67/548/EEC: no classification required

GHS classification (GHS UN rev.3, 2009): no classification required