Tributylphosphine

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In a GLP-compliant OECD 471 study, acceptable responses were obtained for the negative and strain-specific positive control items indicating that the test conditions were adequate and that the metabolic activation system functioned properly. The test item did not induce a significant dose-related increase in the number of revertant (His+) colonies in each of the four tester strains (TA1535, TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in tester strain WP2uvrA both in the absence and presence of S9-metabolic activation. These results were confirmed in a follow-up experiment.

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:

2017-02-10 - 2017-05-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

EC Guideline No. 440/2008. Part B: Methods for the Determination of Toxicity and
other health effects, Guideline B.13/14: "Mutagenicity: Reverse Mutation Test using
Bacteria”. Official Journal of the European Union No. L142, 31 May 2008

Deviations:

yes

Remarks:

Due to a calculation error not the correct composition of the S9-mix was prepared; this deviation in the composition of the S9-mix had no effect on the results of the study.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

Rat liver microsomal enzymes (S9 homogenate)

Test concentrations with justification for top dose:

Dose-range finding test: Eight concentrations, 1.7, 5.4, 17, 52, 164, 512, 1600 and 5000 μg/plate were tested in triplicate
Since the test item was cytotoxic in the dose range finding test/first mutation experiment, an additional dose range finding test was performed with the tester strains TA100 and WP2uvrA, both with and without S9-mix according to the pre-incubation method. Seven concentrations, 1.7, 5.4, 17, 52, 164, 512 and 1600 μg/plate and 5.4, 17, 52, 164, 512, 1600 and 5000 μg/plate were tested in triplicate in the tester strains TA100 and WP2uvrA, respectively.

Direct Plate Assay: Based on the results of the dose-range finding test, the following dose-range was selected for the mutation assay with the tester strains, TA1535, TA1537 and TA98 in the absence and presence of S9-mix: 5.4, 17, 52, 164, 512 and 1600 μg/plate.

Pre-Incubation Assay: Absence of S9-mix: 0.17, 0.54, 1.7, 5.4, 17 and 52 μg/plate; Presence of S9-mix: 1.7, 5.4, 17, 52, 164 and 512 μg/plate.

Vehicle / solvent:

- solvent used: Acetone

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Species / strain:

other: All strains

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Positive controls validity:

valid

Conclusions:

Based on the results of this study it is concluded that Tri-n-butyl phosphine is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.

Executive summary:

In this study, acceptable responses were obtained for the negative and strain-specific positive control items indicating that the test conditions were adequate and that the metabolic activation system functioned properly. The test item did not induce a significant dose-related increase in the number of revertant (His+) colonies in each of the four tester strains (TA1535, TA1537, TA98 and TA100) and in the number of revertant (Trp+) colonies in tester strain WP2uvrA both in the absence and presence of S9-metabolic activation. These results were confirmed in a follow-up experiment.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of an OECD 471 study it is concluded that Tri-n-butyl phosphine is not mutagenic in the Salmonella typhimurium reverse mutation assay and in the Escherichia coli reverse mutation assay.