Registration Dossier

Administrative data

Description of key information

An initial limit dose of 2,000 mg/kg of body weight was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, four additional females were sequentially dosed at the same dose level. Since all animals survived, no additional animals were tested.

Following administration, clinical signs noted for all animals included piloerection, facial staining, hypoactivity, andlor reduced fecal volume. However, all animals recovered by Day 2, and appeared active and healthy for the remainder of the 14-day observation period. No mortality was noted during the study period.

Under the conditions of this study, the acute oral LD50 of Trirmethyl Borate is greater than 2000 mg/kg of body weight in female rats and Trimethyl Borate will not be classified in respect of its acute oral toxicity.

Based on the supplied read-across justificatuion, this result is also relevant for Triethyl Borate.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Referencing ECHA's Read-Across Assessment Framework (RAAF) as basis, an analogue approach is used to assess the read-across potential for the target substance triethyl borate (CAS 150-46-9 , EC 205-760-9) from the source substance trimethyl borate (CAS 121-43-7, EC 204-468-9).
This read-across is based on the hypothesis that source and target substances are structurally similar substances, which have similar toxicological properties because they rapidly hydrolyse to a common product: Boric acid, and to non-common compounds which does not influence the prediction of the property under consideration (based on worst-case approach) worst-case approach).
Boric acid is very well absorbed following oral administration. In the body, boric acid diffuses into body fluids (highly soluble in water, with an extremely low log Kow). Boric acid is not metabolized and over 90% of the boric acid dose administered is excreted in the urine, irrespective of the administration rout.
Reason / purpose for cross-reference:
read-across source
Preliminary study:
not applicable
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was noted during the study period.
Clinical signs:
Following administration, clinical signs noted for all animals included piloerection, facial staining, hypoactivity, andlor reduced fecal volume. However, all animals recovered by Day 2, and appeared active and healthy for the remainder of the 14-day observation period.
Body weight:
All animals gained weight during the study period.
Gross pathology:

No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute oral LD50 of Trimethyl Borate is greater than 2000 mg/kg of body weight in female rats and as per Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, Trimethyl Borate will not be classified. Based on read-across result is also relevant for Triethyl borate
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2004-05-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD TG 425, OPPTS 870.1100 and in accordance with the Principles of Good Laboratory Practice (GLP)
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes
Specific details on test material used for the study:
Name of test material (as cited in study report): Trimethyl borate- Physical state: clear liquid with an alcohol odor- Composition of test material, percentage of components: > 99%- Lot/batch No.: Lot #42Y4A09T, TD#04-001 further identified with PSL Reference Number 040210-3R- Stability under test conditions: Test substance was expected to be stable for the duration of testing.- Storage condition of test material: stored in a tightly closed container, at room temperature
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS- Source: Received from Ace Animals, Inc., Boyertown, PA- Age at study initiation: 11-12 weeks- Weight at study initiation: 221-247 grams at experimental start- Fasting period before study: yes- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conformed to the size recommendations in the Guide for the Care and Use ofLaboratoiy Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.- Diet (e.g. ad libitum): Purina Rodent Chow #5012 was supplied ad-libitum (except during pre-dose fasting)- Water (e.g. ad libitum): Filtered tap water was supplied ad-libitum by an automatic water dispensing system.- Acclimation period: 20-28 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 18-22 °C- Humidity (%): 33-68%- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Individual doses were calculated based on the initial body weights, taking into account the specific gravity (determined by PSL) of the test substance - Specific Gravity - 0.930 g/ml
Doses:
2000 mg/kg
No. of animals per sex per dose:
An initial limit dose of 2,000 mg/kg of body weight was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, four additional females were sequentially dosed at the same dose level. Since all animals survived, no additional animals were tested.
Control animals:
no
Details on study design:
Duration of observation period following administration: 14 days - The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.- Frequency of observations and weighing: Individual body weights of the animals were recorded prior to test substance administration (initial) and again on Days 7 and 14 or (termination) after dosing- Necropsy of survivors performed: yes
Statistics:
not applicable
Preliminary study:
not applicable
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was noted during the study period.
Clinical signs:
Following administration, clinical signs noted for all animals included piloerection, facial staining, hypoactivity, andlor reduced fecal volume. However, all animals recovered by Day 2, and appeared active and healthy for the remainder of the 14-day observation period.
Body weight:

All animals gained weight during the study period.
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.
Other findings:
None
Interpretation of results:
other: not classified
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the acute oral LD50 of Trirnethyl Borate is greater than 2000 mg/kg of body weight in female rats and as per Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, Trimethyl Borate will not be classified
Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with rats to determine the potential for Trimethyl Borate (Lot# Lot #42Y4A09T, TD#04-001, >99% Trimethyl Borate) to produce toxicity from a single undiluted dose via the oral route. An initial limit dose of 2,000 mg/kg of body weight was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, four additional females were sequentially dosed at the same dose level. Since all animals survived, no additional animals were tested.

All animals survived exposure to the test substance and gained body weight. Following administration, clinical signs noted for all animals included piloerection, facial staining, hypoactivity, and/or reduced fecal volume. However, all animals recovered by Day 2, and appeared active and healthy for the remainder of the 14-day observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Under the conditions of this study, the acute oral LD50 of Trirnethyl Borate is greater than 2000 mg/kg of body weight in female rats and as per Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, Trimethyl Borate will not be classified.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1972
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: no data
Deviations:
not specified
Principles of method if other than guideline:
Boric acid was administered orally by gavage to six groups of five male and five female albino Sprague-Dawley rats. The test material was administered as a 50 % w/v suspension in 0.5 % aqueous methyl cellulose at dosage levels of 2.0; 2.5; 3.16; 3.98; 5.01 and 6.31 g/kg bw. Rats were fasted for a period of 3 to 4 h prior to dosage. Animals were observed for mortality and toxic effects at 1, 2, 4, and 24 h and once daily after for a total of 14 days. At teh end of the observation period the surviving animals were weighed sacrificed and autopsies were performed.
GLP compliance:
no
Remarks:
Study pre-dates GLP
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
- Name of test material: Boric acid
- Substance type: Solid
- Physical state: Fine soft white powder
- Analytical purity: > 99 %
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: Males: 267 - 302 g; Females: 214 - 248 g
Route of administration:
oral: gavage
Vehicle:
other: 0.5 % aqueous methyl cellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 % w/v

MAXIMUM DOSE VOLUME APPLIED: 3450 - 4080 mg/kg bw
Doses:
2.0; 2.5; 3.16; 3.98; 5.01 and 6.31 g/kg bw.
No. of animals per sex per dose:

Five animals/group; no further data
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:

Litchfield and Wilcoxon
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
3 450 mg/kg bw
Based on:
test mat.
95% CL:
2 950 - 4 040
Remarks on result:
other: mg boric acid/kg
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
4 080 mg/kg bw
Based on:
test mat.
95% CL:
3 640 - 4 560
Remarks on result:
other: mg boric acid/kg bw
Mortality:
No data
Clinical signs:
Symptoms include sings of CNS depression, ataxia, convulsions, laboured breathing or rapid respiration; blood crust around nose, marked diarrhoea and ptosis.
Body weight:
No data
Gross pathology:

Autopsies indicated congestion of lungs, kidneys and adrenals; inflammation of the pyloric portion of stomach and small intestine.
Other findings:
No data
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 of boric acid for male albino rats was 3450 (2950 - 4040) mg boric acid/kg, equivalent to 604 mg B/kg bw. In female albino rats the acute oral LD50 of boric acid was 4080 (3640 - 4560) mg boric acid/kg, equivalent to 714 mg B/kg bw.
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Acceptable, study with sufficient basic documentation to demonstrate that study meets basic scientific principles and contains enough detail to be able to judge the results reliable as a contribution to the understanding of the acute toxicity of this substance.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
observations for only 24 hours, no necropsy and histopathology reported as carried out.
Principles of method if other than guideline:
The study used both old and young test animals to assess for any differences in sensitivity due to age.
GLP compliance:
not specified
Test type:
standard acute method
Specific details on test material used for the study:
No data
Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Woodlyn Farms, Guelph, Ontario.
- Age at study initiation: young animal cohort: 100 days old. Old animal cohort: 10 - 12 months.
- Fasting period before study: overnight
- Housing: individually in stock cages.
- Diet: ad libitum, standard lab chow (ex Master Fox Cubes, Toronto Elevators Ltd)
- Water: ad libitum, tap
Route of administration:
oral: unspecified
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: Ethanol was given as a 40% w/v solution in water.
Doses:
6 to 8 dose levels with a dose interval of 1.1 used.
- One dose per time period.
- Exposure duration: Not applicable.
No. of animals per sex per dose:
10
Details on study design:
- Duration of observation period following administration: 24 hours
- Necropsy findings: not conducted
Statistics:
LD50 estimated by the moving average method of Weil (Biometrics, 8, 249, 1952) or by the graphical technique of Litchfield and Wilcoxon (J Pharmacol Exp Ther, 96, 99, 1949)
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
10 600 mg/kg bw
95% CL:
> 10 000 - < 11 200
Remarks on result:
other: result for young animals
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
7 060 mg/kg bw
95% CL:
> 6 670 - < 7 460
Remarks on result:
other: result for old animals
Mortality:
All deaths occurred within 24 hours. Individual times not given.
Clinical signs:
Description, severity, time of onset and duration of clinical signs at each dose level were not described.
Other findings:
- Potential target organs: cause of death was respiratory failure.
- Sex comparison: not applicable.
Interpretation of results:
GHS criteria not met
Conclusions:
Old rats were considerably more sensitive than young rats.
Executive summary:

An acute toxicity study examined the effect of age of male rats on the oral LD50. Using a relatively large number of animals and 6 -8 doses, an LD50 value of 10600mg/kg was obtained for young animals (~100 days old) whereas a significantly lower figure of 7060mg/kg was obtained for older rats (~11 -12 months old). Animals were only observed for a period of 24 hours, although it is unlikely that significant deaths would have occurred after this point due to the known toxicokinetics of metabolism. For those animals that died death wa due to respiratory failure.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Read-Across and assessment entities Boric Acid and Ethanol

Additional information

Justification for classification or non-classification

Referencing ECHA's Read-Across Assessment Framework(RAAF) as basis,

the source substance Trimethyl borate (CAS121 -43 -7, EC204 -468 -9)and the target substance Triethyl borate(CAS150 -46 -9, EC205 -760 -9) are structurally similar substances, which rapidly hydrolize to a common product (Boric acid), and to non-common compounds which does not influence the prediction of the properties under consideration (based on worst-case approach), and therefore they will exhibit similar toxicokinetic behaviour.

Under the conditions of this study, the acute oral LD50 of Trirmethyl Borate is greater than 2000 mg/kg of body weight in female rats and as per Guidance to Regulation (EC) No. 1272/2008 on Classification, Labelling and Packaging of substances and mixtures, Trimethyl Borate will not be classified in respect of its acute oral toxicity, and this is also relevant for Triethyl Borate.