Registration Dossier

Administrative data

Description of key information

Acute oral LD50 in rats: 56.57 mg/kg
Acute dermal LD50 in rabbits: >4000 LD50 <8000 mg/kg
Acute inhalation LC0 (no lethality) in rats: >5.18 mg/L at 1 hour; converted to >1.30 mg/L, 4 hour

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Inc, Boyertown, Pennsylvania, USA
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 196-229 g
- Fasting period before study: overnight
- Housing: one/cage in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina rodent chow #5012
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 13-20 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24 deg C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light


IN-LIFE DATES: From: July 11, 2005 To: July 25, 2005
Route of administration:
oral: gavage
Vehicle:
other: mineral oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25% w/w suspension




Doses:
32 and 100 mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 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 or until death occurred.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: 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.
Statistics:
Not reported
Sex:
female
Dose descriptor:
LD50
Effect level:
56.57 mg/kg bw
95% CL:
ca. 32 - ca. 100
Mortality:
All animals survived at 32 mg/kg.
All animals at 100 mg/kg died within three hours of administration.
Clinical signs:
No effects at 32 mg/kg.
Incidence of hypoactivity, hunched posture, piloerection were observed prior to death at 100 mg/kg.
Body weight:
No effects
Gross pathology:
No gross abnormalities were observed at 32 mg/kg.
At 100 mg/kg, intestines were extremely red.
Other findings:
none
Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 was determined to be 56.57 mg/kg.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
56.57 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given
Qualifier:
no guideline available
Guideline:
other: Continuous dynamic exposure method
Principles of method if other than guideline:
A semi-portable chamber was used for exposure. An exhaust fan was utilized to provide an adjustable air flow. Test material was administered into the incoming airstream just before it entered the circular hood of the chamber.
GLP compliance:
no
Test type:
other: Continuous dynamic exposure method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200 g
- Housing: animals were confined individually in cages constructed entirely of 3/8 inch screen to be placed into the chamber; Following exposure, five of the exposed animals and five of the control animals were placed in screen bottom cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of four weeks


Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: a semi-portable exposure chamber similar to those developed by the Public Health Service in the Taft Laboratories at Cincinnati.
- Exposure chamber volume: not reported
- Method of holding animals in test chamber: confined individually in cages constructed entirely of 3/8 inch screen and placed in a central location in the chamber
- Source and rate of air: an exhaust fan was utilized to provide an adjustable air flow through the chamber. Test material was administered into the incoming airstream just before it entered the circular hood of the chamber. Air flow was maintained at 586 liters/air.
- Method of conditioning air: not reported
- System of generating particulates/aerosols: The material was sprayed into the air stream using a Wright Dust Feeder.
- Method of particle size determination: not reported
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: not reported


TEST ATMOSPHERE
Air flow was calculated from the pressure drop across a measured inlet orifice in a steel plate. Because of the quantity of material administered, a certain amount came directly in contact with the inlet pipe and circular hood of the chamber. This material was collected, measued and the amount subtracted from the total material administered when calculating the actual exposure level. The final exposure was calculated in mg per liter by subtracting the amount recovered from upper chamber from the total amount sprayed into the chamber and dividing this difference by the total cubic feet of air circulated through the chamber.


VEHICLE
Not applicable



Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
1 h
Concentrations:
5.18 mg/L air
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days; 5 exposed and 5 control animals were sacrificed 30 minutes after completion of the exposure period. The remaining 5 exposed and 5 control animals were observed for 14 days.
- Frequency of observations and weighing: gross observation at necropsy; weighing not reported.
- Necropsy of survivors performed: yes
- Other examinations performed: histopathological: lungs and trachea removed and preserved in fixative. The lungs were inflated with fixative before removal by clamping off the trachea with a hemostat and injecting the fixative into the trachea between the hemostat and the lungs.
Statistics:
Not reported
Sex:
male
Dose descriptor:
LC50
Effect level:
> 5.18 mg/L air
Exp. duration:
1 h
Mortality:
No deaths
Clinical signs:
other: Not reported
Body weight:
Not reported
Gross pathology:
No effects
Other findings:
- Histopathology: sections of lung and trachea show no tissue pathology. Alterations seen occur in both control and test animals and not considered to be treatment related.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute inhalation LC50 is greater than 5.18 mg/L at 1 hour (converted to > 1.3 mg/l at 4 hours).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
1.3 mg/m³
Quality of whole database:
One non-guideline study did not identify an LC50, but only an LC0 at the highest technically achieved concentration (5.18 mg/l for one hour, extrapolated to 1.3mg/l for 4 hours).

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given
Qualifier:
no guideline available
Principles of method if other than guideline:
Administered by administration under a sleeve of rubber snugly fastened about the clipped trunk of the test animal. Animals were immobilized for 24 hours immediately following treatment. At the end of the exposure period the sleeves were removed and the animals returned to cages for a 2 week observation period.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Housing: individual screen bottom cages
- Weight at study initiation: 2951 - 3980 g
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped trunk
- % coverage: not reported
- Type of wrap if used: rubber sleeve


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no washing
- Time after start of exposure: 24 hours


TEST MATERIAL- no data



VEHICLE no vehicle
Duration of exposure:
24 hours
Doses:
1, 2, 4 and 8 g/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weight initially and once a week for two weeks
- Necropsy of survivors performed: no
Statistics:
not reported
Sex:
male
Dose descriptor:
LD50
Effect level:
>= 4 000 - <= 8 000 mg/kg bw
Mortality:
One animal died at 2000 mg/kg but this was not treatment related. All animals at 8000 mg/kg died on Day 1.
Clinical signs:
Skin at all application sites was completely scabbed at 24 hours with this condition still present at 14 days.
Body weight:
no effects
Gross pathology:
not applicable
Other findings:
not applicable
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 is between 4000 and 8000 mg/kg
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 000 mg/kg bw

Additional information

An acute oral toxicity study, OECD test guideline 425, in rats indicates that sodium borohydride should be regarded as toxic. Symptoms observed at the lethal dose include those considered to be agonal, observed just prior to death. At the lethal dose, it severe irritation of the gastrointestinal tract was reported, signified by reddened intestines. This is indicative of the anticipated reactivity of SBH with gastric acid to release hydrogen and generate heat. Skin at all application sites was completely scabbed at 24 hours in an acute dermal toxicity study. This condition was still present at 14 days. There was no mortality in an acute inhalation study in rats at the highest technically achievable concentration of the study.


Justification for selection of acute toxicity – inhalation endpoint
Only study

Justification for selection of acute toxicity – dermal endpoint
Only study

Justification for classification or non-classification

The test substance is classified as Category 3 based on an acute oral LD50 of 56.57 mg/kg in rats.

The test substance does not meet the CLP classification criteria for dermal or inhalation acute toxicity.