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Reverse Mutation assay (1996). Acceptable, well-documented study report equivalent or similar to OECD 471. Isodecyl Benzoate was tested at 312.5, 625, 1250, 2500, and 5000 ug/plate levels with and without S-9 metabolic activation. Isodecyl Benzoate did not produce evidence of mutagenic activity in the bacterial systems tested, either in the presence or absence of metabolic activator.

In vitro mammalian chromosome aberration test (1995). Acceptable, well-documented study report equivalent or similar to OECD 473 and EU Method B.10 (Mutagenicity - In Vitro Mammalian Chromosome Aberration Test) Human lymphocytes.

First test: 9.8, 19.5, 39.1, 78.1, 156.3, 312.5, 625, 1250, 2500, and 5000 ug/mL levels (w/ and w/out S-9)

Second test:Harvested after 18 hours (w/ S-9) 625, 1250, 2500, and 5000 ug/mL

Second test:Harvested after 18 hours (w/out S-9) 9.8, 19.5, 39.1, 78.1, 156.3, 312.5, 625, 1250, 2500, and 5000 ug/mL

Second test:Harvested after 32 hours (w/ S-9) 625, 1250, 2500, and 5000 ug/mL

Second test:Harvested after 32 hours (w/out S-9) 9.8, 19.5, 39.1, 78.1, 156.3, 312.5, 625, 1250, 2500, and 5000 ug/mL

Third test: Harvested after 18 hours (w/ S-9) 100, 156.3, 225, 312.5 ug/mL

First Test

Toxicity Data:

In the absence of S-9 mix Isodecyl benzoate was toxic, with the relative mitotic index being reduced to 19% of the solvent control value at 156.3 ug/mL. The dose levels selected for metaphase analysis were 19.5, 39.1, and 78.1 ug/mL. The mitotic index was reduced to 53% at 78.1 ug/mL.

In the presence of S-9 mix Isodecyl benzoate was non-toxic in terms of depression of mitotic index. The dose levels selected for analyses were 625, 2500 and 5000 ug/mL.

Metaphase analysis:

In the absence of S-9 mixthere were no statistically significant increases in the proportion of aberrant cells when compared to the solvent control.

In the presence of S-9 mixa statistically significant increase in the proportion of aberrant cells was seen at the highest dose level analysed (5000 ug/mL). The levels of 6.5% and 7.0% excluding and including gap damage, respectively, lay just outside the historical control range (0 0 5.25% excluding gap damage and 0 - 6.25% including gap damage).

Bothpositive control compounds, ethyl methanesulphonate and cyclophosphamide, caused large, statistically significant increases (P<0.001) in the proportion of aberrant cells. This demonstrated the efficacy of the S-9 mix and the sensitivity of the test systems.

Second Test

Toxicity Data:

In the absence of S-9 mixIsodecyl benzoate was toxic with a reduction of the mitotic index to 16% or less when compared to the control at concentrations of 156.3 ug/mL and above. The three dose levels chosen for analysis were 19.5, 39.1, and 78.1 ug/mL.

In the presence of S-9 mixIsodecyl benzoate was non-toxic in terms of depression of mitotic index. The dose levels selected for analysis were the same as for the first test, i.e. 625, 2500 and 5000 ug/mL.

The concentrations of the positive control compounds selected for analysis were ethyl methanesulphonate at 500 ug/mL and cyclophosphamide at 15 ug/mL.

Metaphase analysis:

No statistically significant increases in the proportion of aberrant cells when compared to the solvent control were seen in either the presence or absence of S-9 mix.

Bothpositive control compounds, ethyl methanesulphonate and cyclophosphamide, caused large, statistically significant increases (P < 0.001) in the proportion of aberrant cells.

Second test - 32 hour harvest:

Toxicity data

In the absence of S-9 mixIsodecyl benzoate was toxic at concentrations of 156.3 ug/mL and above, with the relative mitotic index being reduced to 9% or less. The dose level selected for analysis was 78.1 ug/mL 

In the presence of S-9 mixIsodecyl benzoate was non-toxic and the highest dose level, 5000 ug/mL, was selected for analysis.

The concentrations of the positive control compounds selected for analysis were ethyl methanesulphonate and 500 ug/mL and cyclophosphamide at 5 ug/mL.

Metaphase analysis:

No statistically significant increases in the proportion of aberrant cells when compared to the solvent control were seen in either the presence or absence of S-9 mix.

Both positive control compounds, ethyl methanesulphonate and cyclophosphamide, caused large, statistically significant increases (P < 0.001) in the proportion of aberrant cells.

The increase in aberrant cells seen in the first test in the presence of S-9 mix was not considered to be indicative of clastogenic activity for the following reasons:

1 The response did not greatly exceed the upper limit of the historical control range.

2 The response was not reproduced in the second test.

3 The response was not seen at the later harvest time.

 

Third test - 18 hour harvest

Toxicity data:

In the presence of S-9 mixIsodecyl benzoate was non-toxic in terms of depression of mitotic index, at all dose levels. The reduction seen at the middle range of dose levels in the first test was, therefore, considered to be anomalous. The dose levels selected for analysis were 100, 156.3, 225, and 312.5 ug/mL. The highest dose level, 312.5 ug/mL, was selected as it was the lowest insoluble concentration. The lower three dose levels were all soluble. The consentration of cyclophosphamide selected for was 25 ug/mL.

Metaphase analysis:

No statistically significant increases in the proportion of the aberrant cells when compared to the solvent controlwere seen.

The positive control, cyclophosphamide, caused a large, statistically significant increase (P < 0.001) in the proportion of aberrant cells. This demonstrated the efficacy of the S-9 mix and the sensitivity of the test system.

Isodecyl Benzoate did not produce evidence of clastogenic activity in the in vitro cytogenetic test system, either in the presence or absence of metabolic activator. It was concluded that Isodecyl Benzoate showed not evidence of clastogenic activity in the in vitro cytogenetic test system. 

Chromosome aberration, micronucleus assay. Acceptable, well-documented study report equivalent or similar to OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test). (1995).

All animals in all groups were dosed with the standard volume of 20 mL/kg bodyweight or 1280 mg/kg bodyweight. Test substance and negative control were dosed by intraperitoneal injection. Mitomycin C, the positive control, was dosed orally by intragastric gavage at 12 mg/kg bodyweight. The animals in the the postive control group were deprived of diet overnight prior to and two hours after dosing. 15 animals per sex (male/female) 30 animals total per dose (Vehicle/Isodecyl Benzoate; 1280 mg/kg B-wt ), 5 animals per sex (male/female) and 10 animals total per dose (Mitomycin C). Bone marrow smears were obtained from test substance and negative control groups at 24, 48 and 72 hours after dosing. Bone marrow smears were obtained form the positive control group at 24 hours after dosing.

 

Isodecyl benzoate, when adminsitered by intraperitoneal injection at 1280 mg/kg bodyweight, did not cause a substantial increase in the incidence of micronucleated polychromatic erythroytes. Isodecyl benzoate did not show evidence of causing chromosome damage in this in vivo test. Isodecyl benzoate produced bone marrow cell toxicity/depression as indicated by a statistically significant decrease in the ratio of polychromatic to normochromatic erythrocytes obtained for treated animals.


Short description of key information:
CAS RN 131298-44-7 was negative when tested in: the Reverse mutation assay (Ames Test) with S. typhimurium TA 1535, TA 1537, TA 98 and TA 100, with and without S-9 metabolic activation; the In vitro mammalian chromosome aberration test (human lymphocytes, with and witout S-p metabolic activation; and, the Chromosome aberration, mouse micronucleus assay. It did not cause a substantial increase in the incidence of micronucleated polychromatic erythroytes and did not show evidence of causing chromosome damage in this in vivo test. It produced bone marrow cell toxicity/depression as indicated by a statistically significant decrease in the ratio of polychromatic to normochromatic erythrocytes obtained for treated animals.

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

CAS RN 131298-44-7 was negative when tested in: the Reverse mutation assay (Ames Test) with S. typhimurium TA 1535, TA 1537, TA 98 and TA 100, with and without S-9 metabolic activation; the In vitro mammalian chromosome aberration test (human lymphocytes, with and witout S-p metabolic activation; and, the Chromosome aberration, mouse micronucleus assay. It did not cause a substantial increase in the incidence of micronucleated polychromatic erythroytes and did not show evidence of causing chromosome damage in this in vivo test. It produced bone marrow cell toxicity/depression as indicated by a statistically significant decrease in the ratio of polychromatic to normochromatic erythrocytes obtained for treated animals.

No classification for genetic toxicity is indicated according to the general classification and labeling requirements for dangerous substances and preparations (Directive 67-548-EEC) or the classification, labeling and packaging (CLP) regulation (EC) No 1272/2008.