Sodium acrylate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro DNA damage and/or repair study

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

26 Feb 1987 - 15 Jan 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Reference 2

Reference Type:

publication

Title:

Genetic Toxicology of Acrylic Acid.

Author:

McCarthy KL et al.

Year:

1992

Bibliographic source:

Fd. Chem. Toxic. 30: 505-515

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 482 (Genetic Toxicology: DNA Damage and Repair, Unscheduled DNA Synthesis in Mammalian Cells In Vitro)

GLP compliance:

yes

Type of assay:

other: Unscheduled DNA synthesis (UDS)

Test material

Test material information

Constituent 1

Reference substance name:

Acrylic acid

EC Number:

201-177-9

EC Name:

Acrylic acid

Cas Number:

79-10-7

Molecular formula:

C3H4O2

IUPAC Name:

acrylic acid

Specific details on test material used for the study:

- Name of test material (as cited in study report): Acrylic acid
- Analytical purity: > 99.8 %
- Source: Hoechst Celanese Company, Somerville, NJ, USA

Method

Species / strain

Species / strain / cell type:

hepatocytes: primary culture (rat)

Details on mammalian cell type (if applicable):

Primary rat liver cell cultures were derived from the livers of normal adult male Sprague-Dawley rats according to the procedure described by Williams et al. (In Vitro 13: 809-817, 1977):

Metabolic activation:

without

Test concentrations with justification for top dose:

0.01, 0.03, 0.06, 0.1, 0.2, 0.3, 0.4, 0.6 µL/mL

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: phosphate buffered saline

Controls

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

7,12-dimethylbenzanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in medium

DURATION
- Exposure duration: 18-20 hrs (with test article and 3H-thymidine)

NUMBER OF REPLICATIONS: 3


NUMBER OF CELLS EVALUATED: 25 cells in random areas on each of two coverslips per treatment


DETERMINATION OF CYTOTOXICITY
- Method: lactic acid dehydrogenase (LDH) activity

Evaluation criteria:

If the mean net nuclear count was increased by at least five counts over the control, the results for a particular dose level were considered significant. A test article was judged positive if it induced a dose-related response and at least one dose produced a significant increase in the average net nuclear grains when compared to that of the control. In the absence of a dose-response, a test article which showed a significant increase in the mean net nuclear grain count in at least two successive doses was considered positive.

Results and discussion

Test results

Key result

Species / strain:

hepatocytes: Primary Rat Hepatocytes

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

0.4 µL/mL

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

True negative controls validity:

not examined

Positive controls validity:

valid

Any other information on results incl. tables

The test article, acrylic acid, was tested in the Unscheduled DNA Synthesis Test using rat primary hepatocytes. The test article was originally tested at nine dose levels ranging from 0.001 to 3.0 µL/mL and was fully evaluated at five dose levels of 0.01, 0.03, 0.1, 0.2 and 0.3 µL/mL. A repeat assay was conducted using eight dose levels ranging from 0.01 to 0.6 µL/mL and was fully evaluated at seven dose levels of 0.01, 0.03, 0.06, 0.1, 0.2, 0.3 and 0.4 µL/mL. The results of the original UDS assay indicate that under the test conditions, the test article did cause a significant increase in the mean number of net nuclear grain counts (i.e., an increase of at least 5 counts over the control), at the second highest dose level evaluated, 0.2 µL/mL. The remaining dose levels showed no increase in net nuclear counts above the control. Since an analysis of the raw data indicated that there had not been an actual increase in nuclear counts, only a decrease in cytoplasmic counts, a repeat assay was performed. In the repeat assay the test article did not cause a significant increase in mean net nuclear grain counts at any dose level. Therefore, the test article was considered to be negative in this study.

Summary of Repeat UDS Assay:

Treatment [µL/mL]	Relative survival [%]	Average net grains/nucleus	% cells with 5 or more net nuclear grains
Acrylic acid 0.6	26	-	-
Acrylic acid 0.4	90	0.0 ± 1.6	0
Acrylic acid 0.3	94	-0.4± 1.6	0
Acrylic acid 0.2	96	0.1 ± 1.4	0
Acrylic acid 0.1	96	0.1± 0.9	0
Acrylic acid 0.06	97	0.1 ± 1.6	2
Acrylic acid 0.03	99	0.1 ± 1.0	0
Acrylic acid 0.01	100	-0.6 ± 1.9	0
DMBA 10 µg/mL	79	12.6 ± 4.8	100
DMBA 3 µg/mL	88	6.2 ± 3.2	66
DMSO	100	-0.7 ± 1.5	0
PBS	100	0.1 ±1.0	0
Media control	98	-0.2± 1.4	0

DMBA: 7,12- Dimethylbenzanthracene (positive control)

DMSO:Dimethylsulfoxide (vehicle control to positive control)

PBS: Phosphate buffered saline (vehicle control)