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Description of key information

Acute oral and dermal studies have been performed with zinc borate anhydrous and the heptahydrate.  In addition, acute oral, dermal and inhalation studies on an analogue substance have been performed.  Experimental data showed low acute toxicity to zinc borate. The mean of the male and female values were obtained from the key study (oral route; Kreuzmann, 1990).

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:
07/09/1990 to 21/09/1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
other: FIFRA (40 CFR)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: TSCA (40 CFR)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: OECD - Not specified
Deviations:
not specified
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc.
- Age at study initiation: Young adult
- Weight at study initiation: 228 - 301 g
- Fasting period before study: Overnight
- Housing: In groups of five in wire mesh suspension cages.
- Diet: Ad libitum, except for fasting period.
- Water: Ad libitum
- Acclimation period: At least 4 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 h dark/light cycle.

IN-LIFE DATES: From: 07/09/1990 To: 21/09/1990
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 % w/v
Doses:
5 g/kg
No. of animals per sex per dose:
Five/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 gross signs of systemic toxicity and mortality several times during the day of dosing and at least twice daily thereafter for a total of 14 days. Body weights were measured for each animal on the day of dosing, on Day 7 and at the time of necropsy.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs and body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 other: g/kg
Based on:
test mat.
Remarks on result:
other: The LD50 was greater than the limit dose. No clinically relevant mortality was observed.
Mortality:
One death was observed on Day 3 of the observation period but was not deemed clinically relevant.
Clinical signs:
Clinical signs included faecal stains, depression and unkempt fur.
Body weight:
See table.
Gross pathology:
No relevant gross pathology was observed. The gross necropsy findings in the animals that died during the observation period were those generally seen in agonal animals.

Body weight data in male and female rats treated orally with a 50 % w/v formulation of XPI-187 zinc borate in corn oil at a dose level of 5.0 g/kg:

Animal

No.

Sex

Body weight (g)

Body weight change

Day 0 – 14 (g)

Day 0

Day 7

Day 14

1-1761

M

279

229a

ND

N/A

2-*

M

263

323

349

86

3-1763

M

264

309

343

79

4-1764

M

301

339

372

71

5-1765

M

285

238

400

115

Mean (SD)

278 (16)

302 (45)

366 (26)

88 (19)

6-1766

F

238

273

278

40

7-1767

F

249

302

321

72

8-1768

F

252

305

298

46

9-1769

F

228

266

271

43

10-1770

F

241

278

285

44

Mean (SD)

242 (10)

285 (18)

291 (20)

49 (13)

a body weight taken at death and was not used in the calculation of the mean or standard deviation.

* lost ear tag prior to dosing

ND - No data

N/A - Not applicable

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: other: 40 CFR 156
Conclusions:
The acute oral toxicity of XPI-187 zinc borate was evaluated in compliance with the conditions specified in the regulation for the enforcement of the Federal Insecticide, Fungicide and Rodenticide Act (40 CFR), the Toxic Substances Control Act and OECD Guidelines. The acute oral LD50 value was found to be greater than 5.0 g/kg in male and female Sprague-Dawley rats and was greater than the limit dose. The test material was classified in Toxicity Category IV (40 CFR 156) by oral administration.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The study is a GLP compliant and has Klimish score 1.

Acute toxicity: via inhalation route

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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:
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)
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
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
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.
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.
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
4.95 mg/m³
Quality of whole database:
The study is a GLP compliant and has Klimish score 2 (due to read-across).

Acute toxicity: via dermal route

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Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28/08/1990 - 19/10/1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
other: federal Insecticide, Fungicide and Rodenticide Act (40 CFR)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
other: Toxic Substances Control Act (40 CFR)
Deviations:
not specified
GLP compliance:
yes
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:King's Wheel Rabbitry
- Age at study initiation: Young adult
- Weight at study initiation: 2256 - 2438 g
- Housing: Singly in wire mesh suspension cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least 4 days.

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 h dark/ 12 h light cycle

IN-LIFE DATES: From: To:
Type of coverage:
occlusive
Vehicle:
physiological saline
Details on dermal exposure:
TEST SITE
- Area of exposure:
- % coverage:
- Type of wrap if used: The test material was applied to sleeves of rubber dental dam. each sleeve was wrapped around the trunk of the respective animal and secured with staples. An outer layer of gauze was wrapped around the trunk of each animal and secured with tape.

REMOVAL OF TEST SUBSTANCE
- Washing: Any unabsorbed test material remaining on the skin was removed by gentle sponging using a towel moistened with water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 5.0 g/kg
- Concentration: The test material was used as received and moistened with an appropriate volume of physiological saline prior to administration.
- Constant volume or concentration used: No data
- For solids, paste formed: Yes
Duration of exposure:
24 h
Doses:
5 g/kg
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for signs of toxicity and behavioural change once a day with an additional check for viability during the day.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs were noted once daily; body weight was measured on the day of dosing, on Day 7 and at the time of necropsy at the end of the 14-day observaiton period; skin reactions and other evidene of irritaiton or injury were noted once daily.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No deaths were noted during the observation period.
Mortality:
No deaths were noted during the observation period.

The acute dermal toxicity of XPI-187 Zinc Borate was evaluated in compliance with the conditions specified in the regulation for the enforcement of the Federal Insecticide, Fungicide and Rodenticide Act, the Toxic Substances Control Act and the OECD Guidelines

No deaths were noted during the observation period

The acute dermal LD50 value was found to be >5.0 g/kg in male and female New Zealand White rabbits

Body weight data

Animal number

Sex

Body weight (g)

Body weight change (g)

Day 0

Day 7

Day 14

Day 0 – 14

1-939

M

2770

2945

3037

267

2-940

M

3133

3289

3549

416

3-943

M

2919

2868

3119

200

4-943

M

3068

3112

3329

261

5-950

M

2256

2436

2395

139

Mean

 

2839

2930

3086

257

 

 

 

 

 

 

6-959

F

2943

3208

3417

474

7-960

F

3257

3208

3474

217

8-961

F

3438

3249

3727

289

9-962

F

2508

3601

2802

294

10-963

F

3319

3519

3645

326

Mean

 

3093

3231

3413

320

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The acute dermal toxicity of the test substance was evaluated in compliance with the conditions specified in the regulation for the enforcement of the Federal Insecticide, Fungicide and Rodenticide Act 940 CFR) the TSCA (40 CFR) and the OECD guidelines. No deaths were noted during the observation period. The acute dermal LD50 was found to be greater than 5.0 g/kg in male and female New Zealand White rabbits. The test material was classified as Toxicity Category IV (40 CFR 156) by dermal administration.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The study is a GLP compliant and has Klimish score 1.

Additional information

LD50 values of > 5000 mg/kg were recorded for both oral and dermal routes and > 4 mg/L for the acute inhalation study with zinc borate. In each case there were no clinically relevant mortalities and the LD50 exceeded the limit dose. Zinc borate is of low acute toxicity (see toxicokinetic section for read-across justification).


Justification for selection of acute toxicity – oral endpoint
Key study conducted with zinc borate anhydrous.

Justification for selection of acute toxicity – inhalation endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Key study conducted with zinc borate anhydrous.

Justification for classification or non-classification

Zinc borate is not classified for the oral, dermal or inhalation route, as the LD50 values exceed the limit for classification.