Phosphinylidynetrimethanol

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Remarks:

Only four strains of S. typhimurium (TA1535, TA1537, TA98, TA100) were used, data on E.coli WP2 strains or S. typhimurium TA102 are lacking. However, since these strains were mainly included in the recent version of OECD 471 because the four formerly only recommended S. typhimurium strains TA1535, TA1537, TA98 and TA100 may not detect certain oxidising mutagens, cross-linking agents and hydrazines, and this mode of action is not likely to occur based on the chemical structure of the test item, this restriction is considered to be negligible.

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity Tests of Fabric-Finishing Agents in Salmonella typhimurium: Fiber-Reactive Wool Dyes and Cotton Flame Retardants

Author:

MacGregor J.T. et al.

Year:

1980

Bibliographic source:

Environmental Mutagenesis 2:405—418 (1980)

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

only four strains of S. typhimurium (TA1535, TA1537, TA98, TA100) were used

Deviations:

no

Principles of method if other than guideline:

Only four strains of S. typhimurium (TA1535, TA1537, TA98, TA100) were used, data on E.coli WP2 strains or S. typhimurium TA102 are lacking. However, since these strains were mainly included in the recent version of OECD 471 because the four formerly only recommended S. typhimurium strains TA1535, TA1537, TA98 and TA100 may not detect certain oxidising mutagens, cross-linking agents and hydrazines, and this mode of action is not likely to occur based on the chemical structure of the test item, this restriction is considered to be negligible.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Phosphinylidynetrimethanol

EC Number:

213-924-6

EC Name:

Phosphinylidynetrimethanol

Cas Number:

1067-12-5

Molecular formula:

C3H9O4P

IUPAC Name:

[bis(hydroxymethyl)phosphoryl]methanol

Test material form:

liquid: viscous

Details on test material:

yellowish liquid, viscous, turbid
CAS no.: 1067-12-5
Storage conditions: at +10 to +25°C, in the tightly closed original container and stored in a cool, dry and well-ventilated place, protected from heat and sunlight

Specific details on test material used for the study:

no details given

Method

Species / strain

Species / strain / cell type:

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

Metabolic activation:

with and without

Metabolic activation system:

rat liver oxidative enzyme metabolizing system (S-9 mix) with Aroclor-1254-induced rat liver

Test concentrations with justification for top dose:

1000, 100, 10, 0 µg/plate

Vehicle / solvent:

none

Controls

Controls 1

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Aflatoxin B1

Controls 2

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: Aflatoxin B1

Controls 3

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

9-aminoacridine

Controls 4

Untreated negative controls:

no

Negative solvent / vehicle controls:

yes

True negative controls:

no

Positive controls:

yes

Positive control substance:

other: N-methyl1-N-nitro-N-nitrosoguanidine (MNNG)

Details on test system and experimental conditions:

Water was used to dissolve the test item THPO.
Liver homogenate was employed at a level of 0.1 ml per 1.0 ml of S-9 mix.

Rationale for test conditions:

no details given

Evaluation criteria:

no details given

Statistics:

Control values for each strain, both without and with the S-9 mix, were found not to differ significantly from the normal distribution by the Kalmagorov-Smimov goodness-of-fit test (P> 0.2 in each case). Differences between each replicate control value and the mean control value from each individual experiment were also normally distributed, with a better fit in each case than that of the absolute control values. Least significant differences (LSD) of experimental values from concurrently determined control values were based on the variance between sets of replicate control values summed over each set of experiments by strain and S-9 condition as follows: LSD = t√MS, where t is the t-statistic value at a given confidence level with degrees of freedom equal to the number of control data pairs, and MS is the overall variance of individual replicate differences from the mean of each individual experiment summed over all experiments. Within the range of control values, the variance was not dependent on the mean in any strain either without or with the S-9 mix.

Results and discussion

Test results

Test results 1

Key result

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 2

Key result

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 3

Key result

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Test results 4

Key result

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Positive controls validity:

valid

Additional information on results:

none

Applicant's summary and conclusion

Conclusions:

Tris(hydroxymethyl)phosphine oxide (THPO) did not exhibit significant mutagenic activity under the conditions employed.

Executive summary:

The mutageniy activity of the test item Tris(hydroxymethyl)phosphine oxide (THPO) was tested in S. typhimurium strains TA100, TA98, TA1535, and TA1537 with and without metabolic activation using the quantitative top agar overlay technique.

Tris(hydroxymethyl)phosphine oxide (THPO) did not exhibit significant mutagenic activity under the conditions employed.

Finally, an Ames test with the 5th missing strain is not required due to structural considerations: THPO is not a highly reactive agent and is therefore not expected to be a cross-linking agent, has no oxidizing properties and is no hydrazine.