Tris(1,3-dihydroxyprop-2-yl) borate

Endpoint summary

Description of key information

Acute oral, inhalation and dermal toxicity studies have been performed with boric acid.  Experimental data showed boric acid to be of low toxicity. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Meets generally accepted scientific standards with acceptable restrictions. Study conducted on the hydrolysis product of reference substance, boric acid.

Qualifier:

according to guideline

Guideline:

other: No data

Deviations:

not specified

Principles of method if other than guideline:

Boric acid was administered orally by gavage to six groups of five male and five female albino Sprague-Dawley rats. The test material was administered as a 50 % w/v suspension in 0.5 % aqueous methyl cellulose at dosage levels of 2.0; 2.5; 3.16; 3.98; 5.01 and 6.31 g/kg bw. Rats were fasted for a period of 3 to 4 h prior to dosage. Animals were observed for mortality and toxic effects at 1, 2, 4, and 24 h and once daily after for a total of 14 days. At teh end of the observation period the surviving animals were weighed sacrificed and autopsies were performed.

GLP compliance:

no

Remarks:

Study pre-dates GLP

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: Males: 267 - 302 g; Females: 214 - 248 g

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % aqueous methyl cellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 % w/v

MAXIMUM DOSE VOLUME APPLIED: 3450 - 4080 mg/kg bw

Doses:

2.0; 2.5; 3.16; 3.98; 5.01 and 6.31 g/kg bw.

No. of animals per sex per dose:

Five animals/group; no further data

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs

Statistics:

Litchfield and Wilcoxon

Sex:

male

Dose descriptor:

LD50

Effect level:

3 450 mg/kg bw

Based on:

test mat.

95% CL:

2 950 - 4 040

Remarks on result:

other: mg boric acid/kg

Sex:

female

Dose descriptor:

LD50

Effect level:

4 080 mg/kg bw

Based on:

test mat.

95% CL:

3 640 - 4 560

Remarks on result:

other: mg boric acid/kg bw

Mortality:

No data

Clinical signs:

other: Symptoms include sings of CNS depression, ataxia, convulsions, laboured breathing or rapid respiration; blood crust around nose, marked diarrhoea and ptosis.

Gross pathology:

Autopsies indicated congestion of lungs, kidneys and adrenals; inflammation of the pyloric portion of stomach and small intestine.

Other findings:

No data

Interpretation of results:

not classified

Remarks:

Migrated information no data Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 of boric acid for male albino rats was 3450 (2950 - 4040) mg boric acid/kg, equivalent to 604 mg B/kg bw. In female albino rats the acute oral LD50 of boric acid was 4080 (3640 - 4560) mg boric acid/kg, equivalent to 714 mg B/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 765 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

No data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study. Study conducted on the hydrolysis product of reference substance, boric acid.

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: USEPA FIFRA 40 CFR Part 160

Deviations:

not specified

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animlas Inc, Boyertown, PA
- Age at study initiation: Young adult
- Weight at study initiation: Males 205 - 255 g, females 179 - 208 g

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD 3.5 μm ± GSD 1.81 μm


CLASS METHOD
- Rationale for the selection of the starting concentration: ~ 2mg/L was the highest that was obtainable under the conditions of the test.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Concentrations:

Nominal concentration: 2000 mg/m3
Analytical concentration: 2120 ± 140 mg/m3

No. of animals per sex per dose:

5/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs

Statistics:

Not applicable - limit test

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.12 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: This study was carried out to confirm that the highest dose obtainable was 2 mg/L.

Mortality:

No deaths occurred

Clinical signs:

other: Animal observations were limited to the accumulation of test material on the walls of the exposure chamber. During the first 1.5 h of exposure, ocular and nasal discharge, hypoactivity and hunched posture were noted. Ocular discharge and/or nasal discha

Body weight:

No data

Gross pathology:

No specific findings observed, except red lung discolouration consistent with carbon dioxide inhalation caused by the euthanisation technique. All tissues and organs were normal.

Other findings:

No data

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test was performed according to OECD Guideline 403. No deaths occurred. Animal observations were limited due to the accumulation of test material on the walls of the exposure chamber. During the first 1.5 h of exposure, ocular and nasal discharge, hypoactivity and hunched posture were noted. Ocular discharge and/or nasal discharge persisted in most animals after removal from the chamber. All animals recovered by day two after removal from the chamber.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

2 000 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

No data

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study. Study conducted on the hydrolysis product of reference substance, boric acid.

Qualifier:

according to guideline

Guideline:

other: FIFRA (40 CFR 163)

Deviations:

no

GLP compliance:

no

Remarks:

Study pre-dates GLP

Test type:

fixed dose procedure

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan F. Plummer
- Weight at study initiation: 1623 - 2922 g

Type of coverage:

semiocclusive

Vehicle:

physiological saline

Details on dermal exposure:

TEST SITE
- Area of exposure: The skin of all animals was abraded longitudinally every 2 - 3 cm, deep enough to penetrate the stratum corneum, but not cause bleeding.
- % coverage: > 10 % of body surface implied
- Type of wrap if used: Semi occlusive


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Moist towel
- Time after start of exposure: 24 h


TEST MATERIAL
- For solids, paste formed: Yes


VEHICLE
- Amount applied: Substance moistened with 1.5 mL saline

Duration of exposure:

24 h

Doses:

Dosage to 2 g/kg

No. of animals per sex per dose:

5/sex/group

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, histopathology

Statistics:

Not applicable - limit test.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred

Clinical signs:

other: Clinical changes were limited to transient diarrhoea in 2 rabbits and some incidences of erythema (9), and oedema (30), atonia (2), desquamation (4), necrosis, and other evidence of irritation at 23 and ~70.5 h after treatment.

Gross pathology:

No gross necrospy findings were observed. Observations included one animal with gas filled intestine, one animal with pale yellow-coloured kidneys and 5 animals with enlarged or swollen fallopian tubes.

Other findings:

No data

Gross necropsy findings in male and female rabbits at the end of the observation period:

Gross Necropsy Findings	Dosage at 2 g/kg
Number of animals necropsied	10
No gross necropsy findings	5
Intestine
Gas-filled	1
Kidneys
Pale yellow coloured	1
Fallopian tubes
Enlarged or swollen	4
Pale	1
External
Diarrhoea stains	1

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The study was performed according to FIFRA (40 CFR 163). The LD50 > 2000 mg/kg bw indicating no acute dermal toxicity. No deaths occurred. Clinical changes were limited to erythema, oedema, atonia, desquamation, necrosis and some incidences of skin irritation at more than 24 h of treatment.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

The reference substance (BAGE) hydrolyses within less than an hour to its hydrolysis products: Boric acid and glycerol. Therefore, conducting an acute toxicity studies on the reference substance will give a result representative of the hydrolysis products mentioned above.

Boric acid is considered to be the hydrolysis product of main concern, due to its known reproductive/developmental effects. An assessment of the acute toxicity of boric acid has therefore been made based on available study data on boric acid.

Acute Oral Toxicity of Boric acid:

Keller JG (1962) - Rat:

Boric acid was administered orally by gavage to six groups of five male and five female albino Sprague-Dawley rats. The test material was administered as a 50 % w/v suspension in 0.5 % aqueous methyl cellulose at dosage levels of 2.0; 2.5; 3.16; 3.98; 5.01 and 6.31 g/kg bw. Rats were fasted for a period of 3 to 4 h prior to dosage. Animals were observed for mortality and toxic effects at 1, 2, 4, and 24 h and once daily after for a total of 14 days. At the end of the observation period the surviving animals were weighed sacrificed and autopsies were performed.

Symptoms include sings of CNS depression, ataxia, convulsions, laboured breathing or rapid respiration; blood crust around nose, marked diarrhoea and ptosis.

The acute oral LD50 of boric acid for male albino rats was 3450 (2950 - 4040) mg boric acid/kg, equivalent to 604 mg B/kg bw. In female albino rats the acute oral LD50 of boric acid was 4080 (3640 - 4560) mg boric acid/kg, equivalent to 714 mg B/kg bw.

The acute oral LD50 for boric acid for male and female rats was taken as 3765 mg/kg.

Meyding GD (1962):

The LD50 for boric acid was 3160 mg/kg bw.

Long Evans rats showed symptoms of depression, shollow rapid respiration, diarrhoea and piloerection.

Acute Inhalation Toxicity of Boric acid:

Wnorowski G (1997):

The test was performed according to OECD Guideline 403. The top dose used in the study (nominal 2 mg/l, measured 2.12 mg/l) was the highest that was obtainable under the conditions of the test.

The results of the study showed the LC50 to be >2.12 mg/l. There was no lethal effect at the limit dose.

No deaths occurred. Animal observations were limited due to the accumulation of test material on the walls of the exposure chamber. During the first 1.5 h of exposure, ocular and nasal discharge, hypoactivity and hunched posture were noted. Ocular discharge and/or nasal discharge persisted in most animals after removal from the chamber. All animals recovered by day two after removal from the chamber.

This was a repeat study carried out to confirm that the highest dose obtainable was 2 mg/l.

Wnorowski G (1994):

The test was performed according to OECD Guideline 403. The top dose used in the study was 2 mg/L.

The results of the study showed the LC50 to be > 2.03 mg/L

No deaths occurred. Animal observations were limited due to the accumulation of test material on the walls of the exposure chamber. During the first 30 minutes of exposure, ocular discharge, hypoactivity and haunched posture were noted. Ocular discharge and or nasal discharge persisted in most animals after removal from the chamber. All animals recovered by day seven.

Acute Dermal Toxicity of Boric Acid:

Weiner AS et al (1982):

The study was performed according to FIFRA (40 CFR 163). The LD50 was > 2000 mg/kg bw indicating no acute dermal toxicity. No deaths occurred. Clinical changes were limited to erythema, oedema, atonia, desquamation, necrosis and some incidences of skin irritation at more than 24 h of treatment.

Glycerol

Glycerol is the other hydrolysis product of BAGE. It is not classified for human health according to CLP or DSD and is essentially non-toxic. Further evaluation of the acute oral, inhalation and dermal toxicity of glycerol has not been assessed.

Supporting data

Refer to section 13, Toxicological expert report, for further details of the evalaution of the hydrolysis of BAGE and its consequences for toxicity testing.

Justification for selection of acute toxicity – oral endpoint
Study conducted on boric acid, the hydrolysis product of the reference substance, which is of most concern to human health and is most applicable to evaluate.

Justification for selection of acute toxicity – inhalation endpoint
Study conducted on boric acid, the hydrolysis product of the reference substance, which is of most concern to human health and is most applicable to evaluate.

Justification for selection of acute toxicity – dermal endpoint
Study conducted on boric acid, the hydrolysis product of the reference substance, which is of most concern to human health and is most applicable to evaluate.

Justification for classification or non-classification

Boric acid is not classified for acute toxicity for the oral, dermal or inhalation routes, as the LD50 values from the acute oral and dermal toxicity studies exceed the limit for classification (LD50 >2000 mg/kg). In the acute inhalation study no lethal effect was observed at the highest dose obtainable (2 mg/l).