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Description of key information

Acute oral studies have been performed with potassium tetraborate, disodium tetraborate, sodium tetraborate penthydrate and sodium tetraborate decahydrate and the UVCB test item. Acute dermal and inhalation studies have been performed with disodium tetraborate pentahydrate and disodium tetraborate decahydrate. Experimental data showed low acute toxicity to dipotassium tetraborate.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

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: Guideline study with acceptable restrictions.
Qualifier:
according to guideline
Guideline:
other: Regulations for the Enforcement of the Federal Hazardous Substances Act (revised Federal Register) 1964.
Deviations:
not specified
GLP compliance:
no
Remarks:
Study pre-dates GLP
Test type:
standard acute method
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Industries
- Weight at study initiation: 208 to 262 g
- Fasting period before study: 18 h
- Housing: In groups in wire mesh cages suspended above the droppings.
- Diet: Ad libitum
- Water: Ad libitum
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 % w/v
Doses:
0.464, 1.00, 2.15, 4.64 and 10.0 g/kg bw.
No. of animals per sex per dose:
Five
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Frequently during the day of dosing; at least once daily thereafter.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs; body weight at the end of the study
Statistics:
Statistical analysis of the mortality data was by the moving average method.
Sex:
male
Dose descriptor:
LD50
Effect level:
3.69 other: g/kg
Based on:
test mat.
95% CL:
2.71 - 5.01
Mortality:
See table.
Clinical signs:
All of the rats at the 0.464 and 1.00 g/kg levels exhibited normal appearance and behaviour on the day of dosage and throughout the observation period.
Two rats at the 2.15 g/kg level exhibited mucoid diarrhoea on the day of dosage. On the first day post-dosage, three rats exhibited diarrhoea stains. On Day 2 and for the remainder of the study all rats appeared grossly normal.
At the 4.64 g/kg level on the day of dosage, all the rats exhibited depression and mucoid diarrhoea. On the first post-dosage day the surviving rats exhibited depression, depressed righting reflex , diarrhoea stains, hypothermia, laboured respiration and serosanguinous stains around the nose. On the second pos-dosage day the remaining rat exhibited emaciation and diarrhoea stains. The emaciation in this rat lasted through the 4th day post-dosage day, after which he exhibited normal appearance and behaviour.
Following sample administration, all rats at the 10.0 g/kg level exhibited depression and mucoid diarrhoea. Toxic signs increased in intensity and by the end of the working day the three surviving rats exhibited depression, depressed righting, placement and pain reflexes, ataxia, laboured respiration and mucoid diarrhoea. These rats were found dead in the morning of the first post-dosage day.
Body weight:
The weight gains for each group were within the normal limits for the rats of the age, sex and strain used.
Gross pathology:
Gross necropsies performed on all the rats that died revealed external evidence of diarrhoea in all of the rats and excessive salivation stains in three rats. Internally the majority of the rats showed congestion of the lungs, adrenals and kidneys; diffuse irritation of the entire gastrointestinal tract which contained a fluid resembling the sample,; irritation of the peritoneal walls; and evidence of autolytic alterations. The liver of one rat was pale.

Necropsies performed at termination revealed no significant gross pathological alterations.

Mortality during the 14 -day observation period; values are number of animals dead/number of animals tested:

Dose

g/kg

Time of death

Hours

Days

1

2

4

24

2

3

4

5

6

7-14

0.464

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

1.00

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

2.15

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

4.64

0/5

0/5

0/5

3/5

4/5

4/5

4/5

4/5

4/5

4/5

10.0

0/5

1/5

2/5

5/5

-

-

-

-

-

-

LD50, g/kg

3.69; 95 % confidence limits 2.71- 5.01 g/kg

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: other: Regulations for the Enforcememnt of the Federal Hazardous Substances Act, 1964.
Conclusions:
The acute oral toxicity of potassium tetraborate granular was evaluated in accordance with the techniques specified in the Regulations for the enforcement of the federal hazardous Substances Act (Revised Federal Register, 1964). The acute oral LD50 of the test substance in male albino rats was found to be 3.69 g/kg with 95 % confidence limits of 2.71 - 5.01 g/kg bw.
Based on these results, potassium tetraborate granular was classified as toxic by ingestion under the above cited regulations.
Endpoint:
acute toxicity: oral
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 401 (Acute Oral Toxicity)
Deviations:
not specified
Remarks:
This study was carried out to confirm a previous study, that indicated the LD50 was > 2000 mg/kg, where 40 % of the male rats died at 2000 mg/kg. Doses were selected on the basis of clinical observations and time of onset of signs or death previously.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD.BR
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River UK.
- Age at study initiation: 5-8 weeks old
- Weight at study initiation: 143-198 g
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle: Adjusted to weight of animal

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
1600; 2500 mg/kg bw
No. of animals per sex per dose:
Five males per dose.
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:
No data
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Mortality:
None
Clinical signs:
No deaths occurred. No effects at 1600 mg/kg. At 2500 mg/kg, piloerection observed in one animal that recovered by day 2. No other adverse effects were observed.
Body weight:
No data
Gross pathology:
No data
Other findings:
No data
Interpretation of results:
other: No data
Remarks:
Criteria used for interpretation of results: other: No data
Conclusions:
The LD50 for male rats administered the test substance by oral gavage was > 2500 mg/kg bw.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982-11-15 to 1982-12-08
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study with acceptable restrictions Deviations from the guideline OECD 401(1981) - the purity and stability of the test item were missing in the study report -the time interval of clinical observation was not stated - information on the individual body weight of the animals at weekly intervals and at death/sacrifice was missing in the report. Also, information on body weight changes were missing. - necropsy findings of deceased animals were described. It was not clear if sacrificed animals were also macroscopically examined. - number of animals showing clinical signs were not given in the report.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted 1981-05-12
Deviations:
yes
Remarks:
please refer to "Rationale for reliability incl. deficiencies" above
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Zentralinstitut für Versuchstierzucht, Hannover
- Age at study initiation: males: 54-64 days ; females: 53-63 days
- Weight at study initiation: males: 0.127-0.169 kg ; females: 140-0.187 kg
- Fasting period before study: diet withdrawal 16 hours before start of the study
- Housing: caging: Macrolon cages type II; number of animals per cage: 1; bedding: Softwood granulate type 9 ALTROMIN®
- Diet: Standard test animal diet ALTROMIN®
- Water (ad libitum): water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21°C±2°C
- Relative humidity: 50-60%
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
DOSE INTERVAL: in decimal geometric progression
FACTOR: 1.47; 2.15
DOSE VOLUME APPLIED: 2.15

Doses:
males: 464, 681, 1000 and 1470 mg/kg
females: 464, 681, 1000 and 2150 mg/kg
No. of animals per sex per dose:
464 mg/kg: 5 males / 5 females
681 mg/kg: 5 males / 10 females
1000 mg/kg: 10 males / 10 females
1470 mg/kg: 5 males
2150 mg/kg: 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days after administration
- Examinations performed: clinical signs, mortality and gross pathology
Statistics:
Calculation of the LD 50 (probit analysis)*
*References:
- BLISS, C J., The Statistics of Bloassay, Academic Press, New York, 1962
- FINNEY, D.J., Probit Analysis, 2nd Ed., Cambridge Univ. Press, Cambridge 1952
- WEBER, E., Grundriß d. bid. Statistik, G. Fischer-Verlag, Stuttgart, 7. Auflage, 1972
Sex:
female
Dose descriptor:
LD50
Effect level:
608 mg/kg bw
Based on:
test mat.
95% CL:
456 - 813
Sex:
male
Dose descriptor:
LD50
Effect level:
875 mg/kg bw
Based on:
test mat.
95% CL:
685 - 1 116
Mortality:
464 mg/kg: 0/5 males; 0/5 females
681 mg/kg: 1/5 males; 7/10 females
1000 mg/kg: 6/10 males; 8/10 females
1470 mg/kg: 5/5 males
2150 mg/kg: 5/5 females
First deaths occurred already 1 hour after administration of the test product. The time of survival of the deceased animals ranged between this time point and a maximum of 6 days after administration. In the majority deaths occurred between 1 and 24 hours after administration.
Clinical signs:
As signs of toxicity firstly slight to moderate clonic convulsions occurred. In parallel strenuous respiration, mydriasis, and piloerectlon were observed. Following the convulsions, moderate to severe tremor and subsequently decrease of muscle tone as well as loss of righting, pinna, pain, and corneal reflexes were recorded. Ante mortem the respiration was accelerated. The peripheral parts of the body nose tip, paws, and tail were cyanoticly discoloured. Death occurred due to apnoea.
The progress of intoxication was partly acute, partly protracted. The first symptoms of toxicity were seen between 5 and 30 minutes after administration and lasted up to a maximum of 390 minutes or until death. In the lethal dose range the progress of Intoxication was obviously protracted.
Body weight:
no data
Gross pathology:
At necropsy of the deceased animals macroscopically mainly findings at the viscera were found. Stomach and small intestine were particularly affected. They showed redness of the mucosae, accumulation of liquid and gas. Partly the stomach adhered to parts of the small intestine and the adjacent viscera.
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 (male rats): 875 mg/kg (685 - 1116)
LD50 (female rats): 608 mg/kg (456 - 813)
According to the EC-Commission directive 67/548/EEC and its subsequent amendments, the test substance is classified as harmful if swallowed.
According to the EC-Regulation 1272/2008 and subsequent regulations, the test item is classified as Category 4.
Endpoint conclusion
Dose descriptor:
LD50
Value:
608 mg/kg bw

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: Guideline study with acceptable restrictions.
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
The report lacks detail. Since the data is in line with other data on sodium borates, further testing is not warranted in the interests of animal welfare.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hilltop Lab Animals, Scottdale, PS.
- Age at study initiation: Young adults
- Weight at study initiation: Males 253- 278 g; females 218-245 g
Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
MMAD: 3.1 µm + GSD .971 µm.
Top dose: ~ 2 mg/L was the highest that was obtainable under the conditions of the test.
Analytical concentration: 2040 + 160 mg/m³.
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
2040 + 160 mg/m³
No. of animals per sex per dose:
Five/sex/dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Other examinations performed: Clinical signs, pathology.
Statistics:
No data - Limit test
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.04 mg/L air (nominal)
Exp. duration:
4 h
Remarks on result:
other: No lethal effect at limit dose.
Mortality:
None
Clinical signs:
other: Animal observations were limited due to the accumulation of test material on the walls of the exposure chamber. During the first hour of exposure, ocular discharge, hypoactivity and haunched posture were noted. Ocular discharge and a few animals exhibited
Body weight:
No data
Gross pathology:
No specific findings.
Other findings:
No data
Interpretation of results:
other: Not specified
Remarks:
Criteria used for interpretation of results: not specified
Conclusions:
Acute inhalation toxicity limit on disodium tetraborate pentahydrate gave a LC50 > 2.04 mg/L (2g/m3).
Endpoint conclusion
Dose descriptor:
discriminating conc.
Value:
2 030 mg/m³

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards with acceptable restrictions.
Qualifier:
according to guideline
Guideline:
other: This study was carried out to comply with US EPA-FIFRA guidelines at the time and carried out by the US Food and Drug Laboratories to GLP.
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
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: LaCrosse Industries Inc., Schenectady , New York.
- Weight at study initiation: Males: 2.19 +/- 0.27kg; females: 2.29 +/- 0.28kg
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
TEST SITE
- Area of exposure: Area not specified. The back of each rabbit was clipped free of fur prior to treatment.
- Type of wrap if used: Not specified


REMOVAL OF TEST SUBSTANCE
- Washing: Moist towel
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount applied: Dosage to 2 g/kg bw
Duration of exposure:
24 h
Doses:
Dosage to 2 g/kg bw
No. of animals per sex per dose:
Five/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: Clinical signs, pathlogy
Statistics:
Not relevant – Limit test.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
Clinical changes included anorexia and decreased activity in four rabbits, diarrhoea and soft stools in 3 rabbits and nasal discharge in three rabbits.
Body weight:
No data
Gross pathology:
The only finding in one rabbit was abdominal cavity filled with fluid.
Other findings:
No data
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: not specified
Conclusions:
Acute dermal limit study carried out to comply with US EPA-FIFRA guidelines at the time and carried out by the US Food and Drug Laboratories to GLP. The LD50 was > 2000 mg/kg bw indicating no acute dermal toxicity.
Endpoint conclusion
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

LD50 values of >2000 mg/kg and 608 mg/kg were recorded for the oral route for potassium tetraborate and the UVCB test item respectively; >2000 mg/kg for the dermal route for sodium tetraborate pentahydrate and disodium tetraborate decahydrate. An LC50 value > 2 mg/L was recorded for the acute inhalation studies with disodium tetraborate decahydrate and disodium tetraborate pentahydrate. The inhalation figure represents the highest attainable concentration.

One acute oral toxicity study was conducted on potassium tetraborate in rats. The acute oral LD50 of the test substance in male albino rats was found to be 3.69 g/kg with 95 % confidence limits of 2.71 - 5.01 g/kg bw. (Shipp & Young 1975).

Potassium tetraborate 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.

The following acute oral data were obtained:

Potassium tetraborate: 3690 mg/kg

brazing flux: 608 mg/kg

The following acute inhalation data were obtained:

No acute inhalation studies on brazing flux have been conducted. Studies are however available for analogous substances:

Disodium Tetraborate Pentahydrate: >2040 mg (302 mg B) /m3

Disodium Tetraborate Decahydrate: >2030 mg (300 mg B) /m3

The following acute dermal data were obtained:

No acute dermal studies of dipotassium tetraborates have been conducted. Studies were conducted on an analogue substance

Sodium Tetraborate Pentahydrate: >2000 mg/kg bw (296 mg B/kg)

Assessment entity approach

"Brazing fluxes" are mixtures of boron-containing constituents (potassium(fluoro)borates), which undergo chemical exchanges (anion exchange) and condensation reactions (e.g. formation of oligoborates, polyborates) upon mixing and further manufacturing. This results in a complex mixture of potassium borates, which cannot be fully chemically characterised for substance identity. Thus, according to the definition under REACH, such brazing fluxes must be described as a UVCB substance.

 

An assessment entity approach is followed based on the transformation products of this UVCB uppon dissolution in aqueous media. The substance is highly soluble and forms complex boron, potassium and fluoride constituents. The quantitatively predominant transformation productof this UVCB is represented by boric acid, which is assumed to be the determinant of human health effects because of its classification and its toxicity. For this reason, the assessment is based on information for “borates” (including potassium borate, boric acid and other borate substances).

 

Based on the information provided below, it may safely be assumed that under physiological conditions the chemical speciation of most of the unknown potassium boron compounds corresponds to boric acid. Thus, from a chemical point of view, there is no reason to assume that brazing fluxes would behave differently than boric acid and/or borates under physiological conditions.

 

The basis of this assessment entity approach is further justified by the following reasoning:

In aqueous solutions at physiological and acidic pH, low concentrations of simple inorganic borates such as boric acid B(OH)3, potassium pentaborate (K2B10O16*8H2O), potassium tetraborate (K2B4O7*4H2O), disodium tetraborate decahydrate (Na2B4O7.10H2O; borax), disodium tetraborate pentahydrate (Na2B4O7*5H2O; borax pentahydrate), boric oxide (B2O3) and disodium octaborate tetrahydrate (Na2B8O13*4H2O) will predominantly exist as undissociated boric acid. Above pH 9 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 undissociated boric acid. Since other borates dissociate to form boric acid in aqueous solutions, they too can be considered to exist as undissociated 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 can read across in the human health assessment for each individual substance. Conversion factors are given in the table under CSR section 5.1.3, which corresponds to IUCLID section 7.1 (toxicokinetics, metabolism and distribution endpoint summary). Reference:

WHO. Guidelines for drinking-water quality, Addendum to Volume 1, 1998

Justification for classification or non-classification

Acute oral toxicity

Reference Zechel (1983) will be used as key study for acute oral toxicity, and also for classification. The LD50 for brazing flux was determined to be 608 mg/kg bw.

According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the brazing flux test item shall be classified as acute toxic via the oral route (harmful if swallowed, Xn, R22). According to the EC Regulation No. 1272/2008 and subsequent regulations, the test item shall be classified as acute toxic via the oral route (acute tox. 4, H302).

Acute inhalation or dermal toxicity studies with brazing flux are not available, which is why data for the substance dipotassium tetraborate are used in an assessment entity approach. This substance is not classified either for the dermal or the inhalation route, as the LD50/LC50 values exceed the limit for classification.Therefore, according to Directive 67/548/EEC and subsequent regulations as well as EC Regulation No. 1272/2008 and subsequent regulations, classification of the test item for acute dermal or inhalation toxicity is not required.