[No public or meaningful name is available]

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Boric acid

EC Number:

233-139-2

EC Name:

Boric acid

Cas Number:

10043-35-3

Molecular formula:

H3BO3

IUPAC Name:

Boric acid

Details on test material:

- Name of test material: Boric acid
- Molecular formula: H3BO3
- Molecular weight: 61.8
- Smiles notation: B(OH)3
- Substance type: Inorganic
- Physical state: Solid
- Analytical purity: > 99.9 % w/w
- Lot/batch No.: 4H25-3611
- Stability under test conditions: Stable
- Storage condition of test material: At room temperature
- Other: White and odourless; further identified with PSL Code No. E40921-3
- pH 5.1 (1.0 % solution) at 20 ºC
- Solubility: Soluble in water
- Expiration date: None

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.