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Toxicological information

Acute Toxicity: inhalation

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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: see 'Remark'
Remarks:
GLP guideline study. This study is conducted on an analogue substance. Read-across is justified on the following basis: In aqueous solutions at physiological and acidic pH, low concentrations of simple inorganic borates such as boric acid, disodium tetraborate decahydrate, disodium tetraborate pentahydrate, boric oxide and disodium octaborate tetrahydrate will predominantly exist as undissociated boric acid. At about pH 10 the metaborate anion (B(OH)4-) becomes the main species in solution (WHO, 1998). This leads to the conclusion that the main species in the plasma of mammals and in the environment is un-dissociated boric acid. Since other borates dissociate to form boric acid in aqueous solutions, they too can be considered to exist as un-dissociated boric acid under the same conditions. For comparative purposes, exposures to borates are often expressed in terms of boron (B) equivalents based on the fraction of boron in the source substance on a molecular weight basis. Some studies express dose in terms of B, whereas other studies express the dose in units of boric acid. Since the systemic effects and some of the local effects can be traced back to boric acid, results from one substance can be transferred to also evaluate the another substance on the basis of boron equivalents. Therefore data obtained from studies with these borates c Conversion factor for equivalent dose of B Boric acid H3BO3 0.175 Boric Oxide B2O3 0.311 Disodium tetraborate anhydrous Na2B4O7 0.215 Disodium tetraborate pentahydrate Na2B4O7•5H2O 0.148 Disodium tetraborate decahydrate Na2B4O7•10H2O 0.113 Disodium octaborate tetrahydrate Na2B8O13•4H2O 0.210 Sodium metaborate (anhydrous) NaBO2 0.1643 Sodium metaborate (dihydrate) NaBO2•2H2O 0.1062 Sodium metaborate (tetrahydrate) NaBO2•4H2O 0.0784 Sodium pentaborate (anhydrous) NaB5O8 0.2636 Sodium pentaborate (pentahydrate) NaB5O8∙5H2O 0.1832 References: WHO. Guidelines for drinking-water quality, Addendum to Volume 1, 1998.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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.
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

11

27

30

20.4

50.4

6.00

1.94

Yes

22

27

30

20.6

50.6

6.00

1.64

No

32

27

30

20.5

50.5

6.25

2.00

Yes

43

27

30

20.4

50.4

6.00

2.40

No

53

27

30

20.3

50.3

5.75

1.98

Yes

64

27

30

20.2

50.2

4.50

5

-

74

27

30

20.1

50.1

4.00

5

-

84

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

13

1.94

5.8

34

2.00

5.0

55

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

51

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

CR1

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

CR1-0 (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 red1

Females

5404 - 5408

Lungs

Moderately red1

1customarily seen with CO2 inhlation euthanasia procedure

Applicant's summary and conclusion

Interpretation of results:
other: No data
Remarks:
Criteria used for interpretation of results: EU
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.
Read-across is justified on the basis detailed in the rationale for reliability above. This study is therefore considered to be of sufficient adequacy and reliability to be used as a supporting study and no further testing is justified.