Boric acid

Endpoint summary

Description of key information

Acute oral, dermal and inhalation studies have been performed with boric acid.  Experimental data showed low acute toxicity to boric acid. The mean of the male and female values were obtained from the key study (oral route; Keller 1962). The LD50 is equivalent to 658.9 mg B/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

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.

Qualifier:

no guideline followed

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:

GHS criteria not met

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

Quality of whole database:

High quality (there are a lot of reliable studies for different species available).

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

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:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hilltop Lab Animals, Scottdale, PA
- Age at study initiation: Young adult
- Weight at study initiation: Males 245 - 296 g; females 232 - 251 g
- Housing: singly in suspended stainless steel cages with mesh floors which conform to the size recommendations in the Guide for the Care and use of Laboratory Animals DHEW (NIH) No. 86.23. Litter paper was placed beneath the cage and was changed at least 3 times per week.
- Water: Ad libitum by rack-top carboy except during exposure.
- Acclimation period: 22 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 69 - 71 ºF
- Photoperiod (hrs dark / hrs light): 12 h light/dark

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: no data

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Rectangular whole body perspex chamber operated under slight negative pressure
- Exposure chamber volume: 100 L

TEST ATMOSPHERE
- Particle size distribution: An eight-stage Andersen cascade impactor was used to assess the particle size distribution of the test atmosphere. Samples were withdrawn from the breathing zone of the animals on 2 occassions. The filter paper collection stages were weighed before and after sampling to determine the mass collected at each stage. The aerodynamic mass median diamaeter and geometric standard deviation were determined graphically using two-cycle logarithmic probit axes.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

4 h

Remarks on duration:

The exposure period was extended to 4 h and 9 min to provide for the chamber to reach equilibrium (T99). The times for 90 and 99 % equilibrium of the chamber atmosphere were 4.6 and 9.1 min respectively.

Concentrations:

Top dose ~ 2 mg/L, to prevent undue discomfort to the animals.

No. of animals per sex per dose:

5/sex/dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for signs of gross toxicity, behavioural changes and mortality to exposure and every 15 min during the first 30 min of exposure. Additional in chamber animal observations were limited due to the accumulation of the test substance on the walls of the exposure chamber. Upon chamber removal, the animals were examined at least once daily for 14 days. Observations included gross evaluation of of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behaviour pattern. Particular attention was directed to observations of tremors, convulsions, salivation, diarrhoea, sleep and coma.
- Necropsy of survivors performed: yes on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.
- Other examinations performed: Clinical signs, body weight, organ weights and histopathology.

Statistics:

No data

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.03 mg/L air

Based on:

test mat.

Exp. duration:

5 h

Mortality:

No deaths occured.

Clinical signs:

other: 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 discharg

Other findings:

The gravimetric and nominal chamber concentrations were 2.03 and 110.40 mg/L respectively. The mass median aerodynamic diameter was estimated to be 3.7 microns based on graphic analysis of the particle size distribution as measured with an Andersen Cascade Impactor.

Pre-test trial

Trial No.	Compressed Air Pressure (psi)	Compressed Air Volume (Lpm)	Room Air Volume (Lpm)	Total Air Volume (Lpm)	Motor Setting	Chamber Conc. (mg/L)	Particle Size Sampled
1^1	27	30	20.4	50.4	6.00	1.94	Yes
2^2	27	30	20.6	50.6	6.00	1.64	No
3^2	27	30	20.5	50.5	6.25	2.00	Yes
4^3	27	30	20.4	50.4	6.00	2.40	No
5^3	27	30	20.3	50.3	5.75	1.98	Yes
6^4	27	30	20.2	50.2	4.50	^5	-
7^4	27	30	20.1	50.1	4.00	^5	-
8^4	27	30	20.2	50.2	4.00	^5	-

¹Test substance used as received, unground

²Test substance used after grinding for 1 h in a ball mill

³Test substance used after grinding for 3 h in a ball mill

⁴Test substance used after grinding for 24 h in a ball mill

⁵Trial terminated due to the malfunction of the dust generator caused by the test substance

Summary of pre-test exposure trials¹

Trial No.	Chamber Concentration (mg/L)	Mass Median Aerodynamic Diameter (microns)^2
1^3	1.94	5.8
3^4	2.00	5.0
5^5	1.98	3.7

¹ See table above for details of generation sysem

² Figure is an estimation based on graphic analysis of the particle size distribution as measured with an Andersen Cascade Impactor

³ Test substance used as received, unground

⁴ Test substance used after grinding for 1 h in a ball mill

⁵ test substance used after grinding for 3 h in a ball mill

Gravimetric chamber concentrations

Sample No.	Mass Collected (mg)	Airflow Sampled (Lpm)	Collection Time (min)	Chamber concentration (mg/L)
1	11.9	4	2	1.49
2	12.1	4	2	1.52
3	11.8	4	2	1.48
4	8.6	4	2	10.8
5^1	24.8	4	2	3.10
6	17.7	4	2	2.21
7	12.8	4	2	1.60
8	17.5	4	2	2.19
9	19.4	4	2	2.40
10	20.4	4	2	2.55
11	20.3	4	2	2.54
12	16.5	4	2	2.06
13	16.1	4	2	2.01
14	17.2	4	2	2.15
Average ± Standard Deviation				2.03 ± 0.54

¹ due to the extremely low chamber concentrations recorded during samples 1 - 4, diluent air being supplied to the chamber was reduced from 30 to 15 Lpm prior ot sample #5.

Particle size distribution

Stage	Effective cutoff diameter (microns)	% of total particles captured (by weight)	Cumulative (%)^1
Sample 1
0	9.0	5.3	94.7
1	5.8	12.9	81.8
2	4.7	10.1	71.7
3	3.3	31.1	40.7
4	2.1	22.7	17.9
5	1.1	13.6	4.3
6	0.7	3.3	1.0
7	0.4	0.8	0.3
F	0.0	0.3	0.0
Sample 2
0	9.0	9.3	90.7
1	5.8	15.9	74.8
2	4.7	11.0	63.8
3	3.3	24.4	39.4
4	2.1	22.2	17.2
5	1.1	13.8	3.4
6	0.7	2.2	1.1
7	0.4	0.7	0.4
F	0.0	0.4	0.0

¹ percent of particles smaller than corresponding effective cutoff

Summary of particle size distribution

Sample No	Sampling time (min)	MMAD (microns)^1	Geometric Standard Deviation
1	4	3.6	1.82
2	4	6.7	1.87

¹This figure is an estimation based on graphic analysis of the particle size distribution as measured with an Andersen Cascade Impactor

Individual bodyweights

Animal No.	Sex	Bodyweight (g)
		Initial	Day7	Day 14
5399	M	296	361	398
5400	M	257	310	343
5401	M	245	307	349
5402	M	260	316	340
5403	M	262	298	322
5404	F	232	250	261
5405	F	237	258	273
5406	F	236	263	289
5407	F	251	275	260
5408	F	234	267	275

Individual cage-side observations

Animal no.	Finding	Day of occurrence
Males
5399	Ocular discharge	CR^1
	Test substance on fur	CR-0 (20.5 h)
	Nasal discharge	CR-6
	Active and healthy	7-14
5400	Nasal discharge, test substance on fur	CR-0 (20.5 h)
	Active and healthy	2 – 14
5401	Test substance on fur	CR
	Nasal discharge	CR-0 (20.5 h)
	Active and healthy	2-14
5402	Ocular discharge, test substance on fur	CR
	Nasal discharge	CR-0 (20.5 h), 4 - 6
	Piloerection	2 – 3
	Active and healthy	7 - 14
5403	Ocular discharge, test substance on fur	CR
	Nasal discharge	CR-0 (20.5 h)
	Active and healthy	2 – 3, 6 – 14
	Ano-genital staining	4 - 5
Females
5404	Nasal discharge, test substance on fur	CR^1-0 (20.5 h)
	Active and healthy	2 - 14
5405	Test substance on fur	CR-0 (20.5 h)
	Nasal discharge	CR-5
	Active and healthy	6 - 14
5406	Ocular discharge, nasal discharge,  test substance on fur	CR
	Active and healthy	0 (20.5 h)-14
5407	Ocular discharge, test substance on fur	CR
	Nasal discharge	CR-0 (20.5)
	Active and healthy	2 – 14
5408	Test substance on fur	CR
	Active and healthy	0 (20.5 h)-14

Individual necropsy observations

Animal No.	Tissue	Findings
Males
53999 - 5403	Lungs	Moderately red^1
Females
5404 - 5408	Lungs	Moderately red^1

¹customarily seen with CO₂ inhlation euthanasia procedure

Interpretation of results:

GHS criteria not met

Conclusions:

LC50 > 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

2 mg/m³ air

Quality of whole database:

High quality (3 reliable studies available).

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

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: Guideline study.

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:

GHS criteria not met

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

Quality of whole database:

Guideline study.

Additional information

LD50 values of >2000 mg/kg were recorded for both oral and dermal routes and > 2 mg/L for the acute inhalation study. The highest attainable inhalation concentration was 2.12 mg/L.

Boric acid is of low acute toxicity. Although some of the acute oral studies were not of modern standards and were performed prior to the introduction of GLP, they are reproducible across a number of studies and species and of acceptable quality. For acute dermal and acute inhalation some studies do meet the modern GLP standard.

Justification for selection of acute toxicity – oral endpoint
The study meets generally accepted scientific standards with acceptable restrictions.

Justification for selection of acute toxicity – inhalation endpoint
The study is GLP compliant and has Klimisch score of 1.

Justification for selection of acute toxicity – dermal endpoint
Best study available.

Justification for classification or non-classification

Boric acid is not classified for the oral, dermal or inhalation routes, as the LD50 values exceed the limit for classification according to EU CLP Regulation (EC) No 1272/2008.