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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
other: Experimental study with acrylic acid (structural analogue) which is used for read-across (see attached read across justification document in IUCLID section 13)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Sufficiently documented and scientifically acceptable. Justification for read-across: similar chemical structure (see Cemical Safety Report)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Deviations:
yes
Remarks:
no data on quality assurance and data storage
GLP compliance:
not specified
Type of assay:
mammalian cell gene mutation assay

Test material

Constituent 1
Reference substance name:
acrylic acid
EC Number:
201-177-9
Cas Number:
79-10-7
IUPAC Name:
acrylic acid
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): acrylic acid
- Substance type: organic substance
- Physical state: liquid
- Analytical purity: >99.8%
- supplier: Hoechst Celanese Company (Sommerville, NJ, USA)

Method

Target gene:
HGPRT locus
Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
CHO-K1-BH4 cells obtained from Oak Ridge National Laboratory, USA
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced rat liver S-9
Test concentrations with justification for top dose:
0.3, 0.6, 1.0, 1.5, 1.9, 2.4, 2.8 µl/ml
Vehicle / solvent:
phosphate buffer
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar (plate incorporation); preincubation; in suspension; as impregnation on paper disk

DURATION
- Preincubation period:18-25 h
- Exposure duration: 5 h
- Expression time (cells in growth medium): 7-9 day

NUMBER OF REPLICATIONS: 3

NUMBER OF CELLS EVALUATED: 100 cell/60 mm dish

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency
Evaluation criteria:
toxicity (% survival), total mutant colonies, mutants/ 10 exp 6 clonable cells

Results and discussion

Test results
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
concentrations of 2.4 µl/ml and higher caused cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: adjusted to pH 7.5
- Effects of osmolality: osmolarity was measured and dosing solutions of less than 400 mosmol/kg were used.

ADDITIONAL INFORMATION ON CYTOTOXICITY: concentrations of 2.4 µl/ml and higher caused cytotoxicity, concentrations of 2.8 µl/ml were too cytotoxic for evaluation (2% survival).

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Acrylic acid was assessed as not mutagenic in the CHO/HGPRT mutation assay.
Executive summary:

Acrylic acid (>99.8% pure) was tested for gene mutations in the CHO/HGPRT assay.

After incubation of 5 x 10 exp 5 cells/25 -cm² at 37 °C for 18 -24 h the test compound was added to the culture medium. The pH was monitored and adjusted and the osmalarity was measured. Triplicate cultures with and without metabolic activation (S9) were exposed for 5 h at 37 °C. At the end of the exposure period the medium was removed, the cells washed and cultured for an additional 18 -24 h. After adding additional cell for assessing the cytotoxicity the incubation was continued for 7 -9 days. At the end of this expression period a selection for thioguanine resistant mutants was performed.

Concentrations of 2.4 µl/ml and higher caused cytotoxicity, concentrations of 2.8 µl/ml were too cytotoxic for evaluation (2% survival).

The mutation frequencies for all treatments with acrylic acid were within the normal variation of the background. Consequently, acrylic acid was assessed as not mutagenic in the CHO/HGPRT mutation assay.

This result can be extrapolated to magnesium acrylate.

Please refer to the justification for read across in the Chemical Safety Report.