Pentaboron sodium octaoxide

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

In vitro gene mutation studies in bacteria (Stewart, 1991) in vitro gene mutation studies in mammalian cells (Rudd, 1991) and in vitro cytogenicity studies (NTP, 1987) concluded that boric acid is not genotoxic under the conditions of the studies.

 

Cytotoxicity observed at 5 mg/mL in the in vitro gene mutation studies in mammalian cells (Rudd, 1991).

Link to relevant study records

Reference

Reference 1

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

1 (reliable without restriction)

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:

other: Carried out to an internal NTP protocol, which generally complies with OECD guidelines.

Deviations:

not applicable

Principles of method if other than guideline:

Although this was carried out to an internal NTP protocol, it generally complies with OECD guidelines. Other literature data confirm the results. Also based on Galloway et al; 1985.

GLP compliance:

yes

Type of assay:

in vitro mammalian chromosome aberration test

Target gene:

Not applicable

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 mix - Aroclor 1254 induced rat (Sprague-Dawley) liver S9 fraction

Test concentrations with justification for top dose:

With S-9: 500, 1000, 1500 and 2000 μg/mL.
Without S-9: 1000, 1600, 2000 and 2500 μg.

Vehicle / solvent:

Water

Positive controls:

yes

Positive control substance:

mitomycin C

Positive controls:

yes

Positive control substance:

cyclophosphamide

Details on test system and experimental conditions:

METHOD OF APPLICATION: In water
NUMBER OF CELLS EVALUATED: Not stated

Species / strain:

Chinese hamster Ovary (CHO)

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Conclusions:

Test substance is non genotoxic.

Reference 2

Endpoint:

in vitro gene mutation study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study.

Qualifier:

according to guideline

Guideline:

other: 40 CFR Part 158 US-EPA-FIFRA, Section 156.340

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)

Deviations:

not specified

GLP compliance:

yes

Type of assay:

mammalian cell gene mutation assay

Target gene:

Thymidine kinase, TK locus of the L5178Y mouse lymphoma cell line

Species / strain / cell type:

mouse lymphoma L5178Y cells

Details on mammalian cell type (if applicable):

No data

Additional strain / cell type characteristics:

not specified

Metabolic activation:

with and without

Metabolic activation system:

S9 mix or other (Aroclor 1254 induced rat (Fischer 344) liver S9 fraction used at 1 %).

Test concentrations with justification for top dose:

0, 1.2, 1.7, 2.45, 3.5 and 5.0 mg/mL boric acid.

Vehicle / solvent:

No data

Positive controls:

yes

Positive control substance:

3-methylcholanthrene

Positive controls:

yes

Positive control substance:

other: Hycanthone methylsulphonate

Details on test system and experimental conditions:

METHOD OF APPLICATION: ROP plus 5 % heat treated horse serum

NUMBER OF CELLS EVALUATED: Approximately 600/dose

Evaluation criteria:

Mutations at the TK locus

Statistics:

No data

Species / strain:

mouse lymphoma L5178Y cells

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

Concentration related cytoxicity (60 % reduction over controls at 5 mg/mL)

Additional information on results:

Concentration related cytotoxicity (60 % reduction over controls at 5 mg/mL).
Increase in ouabain resistance seen (not significant).

Gene mutation assay results:

Concentration mg/mL	Number of mutant cells per 10^6cells ± SD				Comments give information on cytotoxicity or other
	Exp 1	Exp 2	Exp 1	Exp 2
	-S9	-S9	+S9	+S9
0	54 ± 10	42 ± 1	29 ± 10	36 ± 7
1.2	46 ± 28	38 ± 15	34 ± 0	36 ± 7
1.7	39 ± 17	31 ± 9	41 ± 7	49 ± 4
2.45	27 ± 3	32 ± 9	40 ± 16	36 ± 6	Minor cytotoxicity seen
3.5	31 ± 18	46 ± 1	41 ± 13	41 ± 6	Cytotoxicity seen
5	50 ± 22	41 ± 5	53 ± 2	47 ± 3	Cytotoxicity seen. Increase in + S9 in first study not reproduced.

Conclusions:

The test substance was not mutagenic but cytotoxicity observed at 5 mg/mL (maximum dose level).

Reference 3

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14-05-91 to 12-08-91

Reliability:

1 (reliable without restriction)

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 µg/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 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Species / strain:

S. typhimurium TA 98

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Species / strain:

S. typhimurium TA 1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Species / strain:

S. typhimurium TA 1535

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

In addition, the results of an in vivo bone marrow cytogenetic assay (chromosome aberration assay, O’Loughlin 1991) also showed boric acid to be non genotoxic.

Link to relevant study records

Reference

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

1 (reliable without restriction)

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 relevant results.

Qualifier:

according to guideline

Guideline:

other: US-EPA-FIFRA section 158.340 Guideline 84-2

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

not specified

GLP compliance:

yes

Type of assay:

micronucleus assay

Species:

mouse

Strain:

Swiss Webster

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

Distilled water.

Details on exposure:

Mice given two doses (in 10 mL distilled water) by gavage.

Duration of treatment / exposure:

2 days.

Frequency of treatment:

Animals dosed once per day.

Post exposure period:

No data

Dose / conc.:

0 mg/kg bw/day (actual dose received)

Dose / conc.:

225 mg/kg bw/day (actual dose received)

Dose / conc.:

450 mg/kg bw/day (actual dose received)

Dose / conc.:

900 mg/kg bw/day (actual dose received)

Dose / conc.:

1 800 mg/kg bw/day (actual dose received)

Dose / conc.:

3 500 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

No data

Control animals:

not specified

Tissues and cell types examined:

No data

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

Clinical signs included rough fur and haunched position.

Conclusions:

Interpretation of results: negative
The test substance was not genotoxic.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

All the in vitro data indicate no mutagenic activity. In addition, the single in vivo study on boric acid also indicated no mutagenic activity.

Please also refer to the read-across statement attached to section 13.

Justification for classification or non-classification

No classification according to Regulation (EC) No 1272/2008 is required for sodium pentaborate regarding genotoxicity as all results for boric acid were negative in the tests.