Tributyl borate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Tributyl borate

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium strains TA 98, 100, 1535 and 1537 (NTP method similar to OECD 471).

As Tributyl borate is rapidly hydrolyzed to Boric acid and n-Butanol in the presence of water or moisture in the air (18.3 sec at 21°C), endpoint information of the hydrolysis products n-Butanol and Boric acid is additionally used for the assessment of the genotoxic potential of Tributy borate:

1) Hydrolysis product Boric acid

Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium strains TA 98, 100, 1535, 1537 and 1538 (method: US EPA 40 CFR Part 158, FIFRA, Section 158.340; similar to OECD 471)

2) Hydrolysis product n-Butanol

- Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium strains TA 1535, TA 97, TA 98 and TA 100 (method: Standard NTP protocol)

- Gene mutation (Bacterial reverse mutation assay / Ames test): negative with and without activation in Salmonella typhimurium strain TA 102 (method: equivalent or similar to OECD 471)

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

other: experimental study on hydrolysis product Boric acid

Adequacy of study:

key study

Study period:

14-05-91 to 12-08-91

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP and in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not effect the quality of the relevent results.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

There is a failure to justify the maximum concentration of 2500 ug/plate

Qualifier:

according to guideline

Guideline:

other: US EPA 40 CFR Part 158; FIFRA, Section 158.340

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EPA OPP 84-2

Deviations:

not specified

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Target gene:

Histidine

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Species / strain / cell type:

S. typhimurium TA 1538

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

Aroclor 1254 induced rat liver S9 at 4 % and 10 %

Test concentrations with justification for top dose:

10; 50; 100; 1000; 2500 μg/plate

Vehicle / solvent:

Water

Positive controls:

yes

Positive control substance:

sodium azide

Positive controls:

yes

Positive control substance:

9-aminoacridine

Positive controls:

yes

Positive control substance:

2-nitrofluorene

Positive controls:

yes

Positive control substance:

other: 2-Anthramine

Details on test system and experimental conditions:

METHOD OF APPLICATION: In water

DURATION
- Preincubation period: None

Evaluation criteria:

No data

Statistics:

No data

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Species / strain:

S. typhimurium TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Additional information on results:

No data

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Conclusions:

The study was performed according to Guideline 84-2 and is comparable to OECD 471. The test substance was not mutagenic in any of the strains tested with or without metabolic activation.

Interpretation of results: negative.

Reference 2

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

not specified

Principles of method if other than guideline:

NTP Ames test; method modified by Yahagi et al. (1975) (Preincubation procedure)

GLP compliance:

no

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

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

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Test concentrations with justification for top dose:

- 0.03300 mg/pl - 7.70000 mg/pl
- justification for maximum concentration of 7.7 mg/plate: not specified

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

not specified

Key result

Species / strain:

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

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

not specified

Untreated negative controls validity:

not specified

Positive controls validity:

not specified

Conclusions:

negative

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

other: experimental study on hydrolysis product n-Butanol

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Principles of method if other than guideline:

Ames test with S. typhimurium TA 102 as described by Maron and Ames (1983) and as specified for TA102 by D. Levin et al . (1982).

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium TA 102

Metabolic activation:

with and without

Metabolic activation system:

S9 mix from livers of Aroclor 1254-induced Sprague-Dawley rats

Test concentrations with justification for top dose:

up to 5000 µg/plate

Details on test system and experimental conditions:

The compounds were tested in at least 2 independent experiments using 5 doses and 3 plates per dose.

Key result

Species / strain:

S. typhimurium TA 102

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: up to limit dose or to precipitating or cytotoxic doses

Remarks on result:

other: all strains/cell types tested

Conclusions:

negative with and without activation

Reference 4

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

other: experimental study on hydrolysis product n-Butanol

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods

Remarks:

missing strain to detect oxidising/ cross-linking agents

Principles of method if other than guideline:

Standard NTP protocol.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

other: S. typhimurium TA 1535, TA 97, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

10% and 30% hamster liver, 10% and 30% rat liver

Test concentrations with justification for top dose:

0, 33, 100, 333, 1000, 3333, 6666 and 10000 µg/plate

Vehicle / solvent:

DMSO

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: see "details on test system"

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

Positive control chemicals used in NTP Ames tests:

For strains tested in the absence of S9
TA98, 2-nitrofluorene or alternatively, TA98 and TA1538, 4-nitro-o-phenylenediamine
TA100 and TA1535, sodium azide
TA97 and TA1537, 9-aminoacridine

For strains tested with S9
All strains, 2-aminoanthracene (or occasionally, sterigmatocystin)

Key result

Species / strain:

other: S. typhimurium TA 1535, TA 97, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

slight toxicity was observed in TA98 and TA100 at the highest tested dose with metabolic activation (30%)

Additional information on results:

In none of the treatments, the maximum revertant factor exceeded a value of 1.5, indicating that the test substance is not mutagenic in the Ames test under the tested conditions.

Remarks on result:

other: all strains/cell types tested

Conclusions:

not mutagenic (negative with and without activation)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available in vitro data for the target substance Tributyl borate and the hydrolysis products n-Butanol and Boric acid, the substance Tributyl borate is not genotoxic and does not require classification according to Regulation 1272/2008/EC.