Iotroxic acid

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In a reverse bacterial mutation assay, the test item was examined for mutagenic potential employing Salmonella typhimurial strains TA1535, TA1537, TA1538, TA98 and TA100 and Saccharomyces cereviciae strain D4 at test concentrations of 1, 10, 50, 100 and 500 µL / plate.

The test compound exhibited slight toxicity with the strains TA-l535 and TA-lOO at the 500 µl dose level. The results.of the tests conducted on the compound in the absence of a metabolic activation system were all negative. The results of the tests conducted on the compound in the presence of a rat liver activation system were all negative. Hence, in this study, it was demonstrated that the test substance is non mutagenic.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1978-10-23 1979-01-17

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Specific details on test material used for the study:

- Name used in the test report: Biliscopin minor
- Physical appearance: Clear colorless liquid

Target gene:

Histidine locus

Species / strain / cell type:

S. typhimurium, other: TA1535, TA1537, TA1538, TA98 and TA100

Details on mammalian cell type (if applicable):

MEDIA USED
- Type and identity of media used: Selective agar plates

Species / strain / cell type:

Saccharomyces cerevisiae

Remarks:

D4

Details on mammalian cell type (if applicable):

MEDIA USED
- Type and identity of media used: Selective agar plates

Metabolic activation:

with and without

Metabolic activation system:

S9 homogenate

Test concentrations with justification for top dose:

1, 5, 10, 50, 100 and 500 µL

Vehicle / solvent:

DMSO

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO (50 µL / plate)

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-METHYL,N-NITRO,N—NITROSOGUANIDINE

Remarks:

-S9: TA1535, TA100, D4,10 µg / plate

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO (50 µL / plate)

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

-S9, TA1537, 50 µg / plate

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO (50 µL / plate)

True negative controls:

no

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Remarks:

-S9, TA1538, TA98, 10 µg / plate

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

DMSO (50 µL / plate)

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: 2-anthramine

Remarks:

+S9: TA1535, TA1537, TA1538, TA98, TA100, D4, 2.5 µg / plate

Details on test system and experimental conditions:

METHOD OF APPLICATION:
- Plate Test: Agar Incorporation: Approximately l08 cells from an overnight culture of each indicator strain were added to separate test tubes containing 2.0 ml molten nagar supplemented with biotin and a trace of histidine. For nonactivation tests, at least 4 dose levels of the test compound
added to the contents of the appropriate tubes and poured over the surfaces of selective-agar plates. In activation tests, at least 4 dose levels of the test chemical were added to the appropriate tubes with cells. Just prior to pouring, an aliquot of reaction mixture (0.5 ml containing the 9,000 x g_liver homogenate)
was added to each of the activation overlay tubes, which were then mixed, and the contents poured over the surface of a
minimal agar plate and allowed to solidify. The plates were incubated for 48 hrs at 37°C and scored for the number of colonies growing on each plate“ 04 yeast plates were incubated at 30°C for 3>5 days and then scored. Positive and solvent controls using both directly active positiva chemicals and those that require metabolic activation were run with each assay‘


NUMBER OF REPLICATIONS: 2


DETERMINATION OF CYTOTOXICITY
- Method: Relative total growth

Rationale for test conditions:

Not specified

Evaluation criteria:

EVALUATION CRITERIA

- Evaluation Criteria for Ames Assay: Because the procedures used to evaluate the mutagenicity of the test chemical are semiquantitative, the criteria used to determine positive effects are inherently subjective and are based primarily on a historical data base."Most data sets are evaluated using the
following criteria: .
- l. Strains TA-l535, TA-1537 and TA-1538: If the solvent control value is within the normal range, a chemical that.produces a positive dose response over three concentrations with the lowest increase equal to twice the solvent control value is considered to be mutagenic.
- Strains TA-98, TA-lOO and D4: If the solvent control value is within the-normal range, a chemical that produces a positive dose response over three concen rations with the highest increase equal to twice the solvant control value for TA-lOO and.2-3 times the solvent control value for strains TA-98 and D4 is considered to be mutagenic. For these strains, the dose-response increase should start at approximately the solvent control value.

Statistics:

Not specified

Key result

Species / strain:

S. typhimurium, other: TA1535, TA1537, TA1538, TA100 and TA98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Key result

Species / strain:

Saccharomyces cerevisiae

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

not specified

Untreated negative controls validity:

valid

Positive controls validity:

valid

Conclusions:

In this study, the test compound, Biliscopin minor, did not demonstrate genetic activity in any of the assays conducted in this evaluation and was considered not mutagenic under these test conditions.

Executive summary:

In a reverse bacterial mutation assay, the test item was examined for mutagenic potential employing Salmonella typhimurial strains TA1535, TA1537, TA1538, TA98 and TA100 and Saccharomyces cereviciae strain D4 at test concentrations of 1, 10, 50, 100 and 500 µL/plate.

The test compound exhibited slight toxicity with the strains TA1535 and TA100 at the 500 µL dose level. The results.of the tests conducted on the compound in the absence of a metabolic activation system were all negative. The results of the tests conducted on the compound in the presence of a rat liver activation system were all negative. Hence, in this study, it was demonstrated that the test substance is non mutagenic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

In a reverse bacterial mutation assay, the test item was examined for mutagenic potential employing Salmonella typhimurial strains TA1535, TA1537, TA1538, TA98 and TA100 and Saccharomyces cereviciae strain D4 at test concentrations of 1, 10, 50, 100 and 500 µL / plate.

The test compound exhibited slight toxicity with the strains TA-l535 and TA-lOO at the 500 µl dose level. The results.of the tests conducted on the compound in the absence of a metabolic activation system were all negative. The results of the tests conducted on the compound in the presence of a rat liver activation system were all negative. Hence, in this study, it was demonstrated that the test substance is non mutagenic.

Justification for classification or non-classification

Based on the available data, the test substance, Iotroxic acid, does not warrant classification for mutagenecity.