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Administrative data

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:
26/01/1996 to 14/03/1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP guideline study. Read-across is justified on the following basis: The family of zinc borates that include Zinc Borate 500, Zinc Borate 2335 and Zinc Borate 415 (also known as Zinc Borate 411). Zinc borate 500 is anhydrous Zinc Borate 2335 and Zinc Borate 415 has different zinc to boron ratio. Zinc borate 2335 (in common with other zinc borates such as Zinc borate 415 and 500) breaks down to Zinc Hydroxide (via Zinc oxide) and Boric Acid, therefore the family of zinc borates shares the same toxicological properties. Zinc borates are sparingly soluble salts. Hydrolysis under high dilution conditions leads to zinc hydroxide via zinc oxide and boric acid formation. Zinc hydroxide and zinc oxide solubility is low under neutral and basic conditions. This leads to a situation where zinc borate hydrolyses to zinc hydroxide, zinc oxide and boric acid at neutral pH quicker than it solubilises. Therefore, it can be assumed that at physiological conditions and neutral and lower pH zinc borate will be hydrolysed to boric acid, zinc oxide and zinc hydroxide. Hydrolysis and the rate of hydrolysis depend on the initial loading and time. At a loading of 5% (5g/100ml) zinc borate hydrolysis equilibrium may take 1-2 months, while at 1 g/l hydrolysis is complete after 5 days. At 50 mg/l hydrolysis and solubility is complete (Schubert et al., 2003). At pH 4 hydrolysis is complete. Zinc Borate 2335 breaks down as follows: 2ZnO • 3B2O3 •3.5H2O + 3.5H2O + 4H+ ↔ 6H3BO3 + 2Zn2+ 2Zn2+ + 4OH- ↔ 2Zn(OH)2 ____________________________________________________________ Overall equation 2ZnO • 3B2O3 •3.5H2O + 7.5H2O ↔ 2Zn(OH)2 + 6H3BO3 The relative zinc oxide and boric oxide % are as follows: Zinc borate 2335:zinc oxide = 37.45% (30.09% Zn) B2O3 = 48.05% (14.94% B) Water 14.5% Zinc borate 415: zinc oxide = 78.79%; (63.31% Zn) B2O3 = 16.85% (5.23% B) Water 4.36% Zinc borate, anhydrous: Zinc oxide = 45 % B2O3= 55% (17.1 % B)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996
Report date:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
not specified
GLP compliance:
yes
Test type:
fixed concentration procedure

Test material

Constituent 1
Reference substance name:
149749-62-2
Cas Number:
149749-62-2
IUPAC Name:
149749-62-2
Details on test material:
- Name of test material: Firebrake 415 (Diboron tetrazinc heptaoxide monohydrate).
- Lot/batch No.: B3H23 Batch 20B
- Analytical purity: 100 %
- Physical state: White powder
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent.
- Age at study initiation: 8 to 10 weeks old.
- Weight at study initiation: Males 2534 - 283 g; females 206 to 245 g
- Fasting period before study:
- Housing: Groups of five by sex in solid floor polypropylene cages with stainless steel lids.
- Diet: Ad libitum with the exception of the exposure period.
- Water: Ad libitum with the exception of the exposure period.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C):21 ± 2 °
- Humidity (%): 55 ± 15 %
- Air changes (per hr): 15/h
- Photoperiod (hrs dark / hrs light): 12 h dark/light cycle

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
- Exposure chamber volume: Approximately 30 L.
- Method of holding animals in test chamber: Easch rat was held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber "o" ring.
- Source and rate of air: A metered compressed air supply was connected to the dust generator.
- Method of conditioning air: Supplied by means of an oil-free compressor and was passed through a water trap and respiratory quality filters before being introduced to the dust feed.
- System of generating particulates/aerosols: A dust atmosphere was generated using a rotating brush dust generator located at the top of the exposure chamber.
- Method of particle size determination: The particle size of the generated atmosphere of the test material inside the exposure chamber was determined three times during the exposure using a Cascade impactor consisting on six impactor stages with stainless steel collection substrates (10, 6, 3.5, 1.6, 0.9 and 0.5 μm cutoff) and a backup glass fibre filter housed in an aluminium sampler. The sampler was temporarily sealed in a sampling port in the animals' breathing zone. Exposure chamber air was drawn through the Cascade Impactor using a vacuum pump for a suitable time period.
- Treatment of exhaust air: The extract from the exposure chamber passed through a "scrubber" trap and was connected with a high efficiency filter to a metered exhaust system.
- Temperature, humidity, pressure in air chamber: The chamber was maintained under negative pressure. The temperature and relative humidity inside the chamber were measured by an electronic thermometer/humidity meter located in a vacant port in the animas' breathing zone of the chamber and recorded every 30 min throughout the test.

TEST ATMOSPHERE
- Brief description of analytical method used: Homogeneity of test atmosphere as not specifically determined during this study, but chambers of the same design have been fully validated and shown to produce evenly distributed atmosphere in the animals' breathing zone with a wide variety of test materials. Prior to the start of the study, test material atmospheres were generated within the exposure chamber. During these periods air flow settings and test material input were varied to achieve the required atmospheric concentrations. The chamber concentration was estimated at regular intervals during the exposure period. The gravimetric method used employed glass fibre filters placed in a filter holder temporarily sealed in a vacant port in the exposure chamber in the animals' breathing zone. Exposure chamber air was drawn through the filter at a measured rate using a vacuum pump. Each filter was weighed before and after sampling in order to calculate the weight of collected test material.
- Samples taken from breathing zone: Yes

TEST ATMOSPHERE
- Particle size distribution: The particle size of the generated atmosphere of the test material inside the exposure chamber was determined three times during the exposure using a Cascade impactor consisting on six impactor stages with stainless steel collection substrates (10, 6, 3.5, 1.6, 0.9 and 0.5 μm cutoff) and a backup glass fibre filter housed in an aluminium sampler. The sampler was temporarily sealed in a sampling port in the animals' breathing zone. Exposure chamber air was drawn through the Cascade Impactor using a vacuum pump for a suitable time period.
The collection substrates were weighed before and after sampling and the weight of test material, collected at each stage, calculated by the difference. From the results obtained the weight distribution of particles in the size range > 10 μm, 10 to 6 μm, 6 to 3.5 μm, 1.6 to 0.9 μm and 0.9 to < 0.5 μm.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD = 2.5 μm; GSD = 0.49 μm; mean achieved atmosphere concentration 4.95 mg/L), inhalable fraction (% < 4 μm) 74.0.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Remarks on duration:
Following an appropriate equilibration period.
Concentrations:
5.0 mg/L.
No. of animals per sex per dose:
Five/sex/group (single group)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes full external and internal examination.
- Other examinations performed: Clinical signs were observed at hourly intervals during the exposure, immediately on removal from the restraining tubes at the end of the exposure, one h after termination of the exposure and once daily for 14 days; body weight prior to treatment on the day of exposure and on Days 7 and 14.
Statistics:
Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, necropsy findings, body weight changes, morality and other toxicological effects. Using the mortality data obtained, an estimate of the acute inhalation median lethal concentration of the test material was made.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
4.95 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: The LC50 exceeded the limit dose. There was no mortality at the concentration tested.
Mortality:
There was no mortality at the concentration tested.
Clinical signs:
other: During exposure wet fur was commonly noted. On removal from the chamber hunched posture and piloerection were additionally common and there were signs of ptosis, laboured respiration and an isolated incident of red/brown staining around the snout. One ho
Body weight:
Normal body weight gain was noted during the study.
Gross pathology:
With the exception of one female which showed dark patches and dark foci on the lungs, no abnormalities were detected at necropsy.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
No deaths occurred in a group of ten rats exposed to a mean achieved concentration of 4.95 mg/L. It was therefore considered that the LC50 of the test material Firebrake 415 in the Sprague-Dawley strain rat was greater than 4.95 mg/L.
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 key study.

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