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Administrative data

Description of key information

Studies of acute oral and acute dermal toxicity are available for BEPD.

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:
17 December 1987 to 6 January 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline and GLP-compliant proprietary study
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Rats [Crl: CD (SD) BR] were supplied by Charles River UK Limited, Margate, Kent, England. All rats were four to six weeks old with a body weight range of 103 to 150 g prior to dosing.
Route of administration:
oral: gavage
Vehicle:
other: Aqueous methylcellulose 1% w/v
Details on oral exposure:
Animals were dosed at constant volume 20 ml/kg bw (concentrations of 10, 16 or 25% w/v to achieve dose levels of 2.0, 3.2 and 5.0 g/kg)
Doses:
2.0, 3.2 and 5.0 g/kg bw.
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
Mortality and clinical signs were checked frequently on the day of dosing and daily thereafter. Bodyweights were recorded weekly and at death. The animals were subjected to gross necropsy at the end of the observation period.
Statistics:
The LD50 was calculated using the method of Finney, Probit analysis (1971).
Preliminary study:
Dose levels were based on the results of a range finding study performed at 1.0 and 4.0 g/kg bw.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 900 mg/kg bw
95% CL:
2 200 - 3 600
Sex:
male
Dose descriptor:
LD50
Effect level:
3 000 mg/kg bw
95% CL:
2 100 - 4 200
Sex:
female
Dose descriptor:
LD50
Effect level:
2 800 mg/kg bw
95% CL:
1 900 - 3 800
Mortality:
Death occurred by Day 2 at 2.0 g/kg bw (1 male), 3.2 g/kg bw (2 males and 5 females) and 5.0 g/kg bw (5 males and 4 females). The majority of deaths occurred within 2 hours of dosing.
Clinical signs:
Clinical signs observed included piloerection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate, ptosis, pallor of extremities and prostrate. These were observed in rats at all dose levels, predominantly within the first six hours following administration. Abnormal body carriage persisted to Day 2 in the high dose group but all signs had resolved within 48 hours of dose administration.
Body weight:
One female dosed at 2.0 g/kg bw and one survivng female dosed at 5.0 g/kg bw made a low gain in bodyweight during the first week of the study. All other surviving rats achieved anticipated bodyweight gains throughout the study.
Gross pathology:
Gross necropsy of all animals (decedents or survivors) revealed no macroscopic abnormalities on any of the rats.
Other findings:
None

Study summary: Acute toxicity in the rat

Group

Dose level (g/kg bw)

Mean bodyweight (g)

% mortality

Day 1

Day 8

Day 15

Male

2.0

122

196

255

20

Female

115

161

188

0

Male

3.2

147

242

302

40

Female

127

n/a

n/a

100

Male

5.0

143

n/a

n/a

100

Female

128

n/a

n/a

80

LD50value

2.9 g/kg bw

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of BEPD in the rat was found to be 2.9 (2.2 - 3.6) g/kg bw for males and females combined. The median lethal dose exceeds the limit dose level of 2000 mg/kg bw and so no classification is necessary for BEPD according to EU criteria.
Executive summary:

BEPD was administered by gavage to groups of Sprague-Dawley rats (5/sex) at dose levels of 2.0, 3.2 and 5.0 g/kg bw. Animals were observed for 15 days. Death occurred at 2.0 g/kg bw (1 male), 3.2 g/kg bw (2 males and 5 females) and 5.0 g/kg bw (5 males and 4 females) within 1 -24 hours of dosing. Signs of toxicity (including piloerection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate, ptosis, pallor of extremities and prostrate) were observed at all dose levels. One female dosed at 2.0 g/kg bw and one surviving female dosed at 5.0 g/kg bw had low bodyweight gain during the first week of the study. All other surviving rats gained bodyweight over the study period. Gross necropsy decedent and surviving rats revealed no macroscopic abnormalities. The acute oral LD50 of BEPD in the rat was found to be 2.9 (2.2 - 3.6) g/kg bw for males and females combined, under the conditions of this study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 900 mg/kg bw
Quality of whole database:
Only study available for this endpoint

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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:
6 March to 31 May 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Proprietary non-GLP study conducted according to internal SOP, comparable to current guidelines.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Principles of method if other than guideline:
The study was comparable to the OECD guideline. The authors report that there were no deviations from the SOP.
GLP compliance:
no
Remarks:
The study was not GLP, however it was subject to a quality assurance inspection
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CD(SD)BR VAF/Plus
Sex:
male/female
Details on test animals and environmental conditions:
The animals were male and female CD(SD)BR VAF/Plus rats, with an initial body weight range of 153-163 g in males, and 158-171 g in females. Individuals were identified by metal ear tages and cage number.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The test substance was moistened with distilled water prior to application. The hair was removed from the skin of the rats with electric clippers. A single dose was applied and an occlusive wrap was sued to hold the test substance against the skin for 24 hours. At the end of the exposure period the application site was washed with running water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
10 rats (5 males and 5 females)
Control animals:
no
Details on study design:
Following the exposure period, the rats were observed for clinical signs and mortality for 2 weeks. Body weight gain was measured weekly. Surviving rats were sacrificed at the end of the 14 day observation period and subjected to gross necropsy.
Statistics:
Statistics were not necessary (limit test; only 1 dose used).
Preliminary study:
Not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
There were no mortalities during the exposure period or the 14 day observation period.
Clinical signs:
No abnormal clinical signs were observed.
Body weight:
All rats gained weight during the 14 day observation period.
Gross pathology:
No treatment-related changes were observed at necropsy. All other lesions observed at necropsy were not considered treatment-related and no tissue was collected for microscopic examination.
Other findings:
No other findings were reported.

The authors concluded that based on weight gain, survival and the absence of clinical signs, no signs of percutaneous absorption (leading to systemic toxicity) were evident.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 of BEPD to rats is >2000 mg/kg bw.
Executive summary:

The acute dermal toxicity of 2 -Butyl-2 -ethyl-1,3 -propanediol (BEPD) was determined in a limit test with 5 male and 5 female CD(SD)BR VAF/Plus rats. The test substance was applied (after moistening with distilled water) to the shaved skin of the rats, in a single dose of 2000 mg/kg bw. The test substance was held in place for 24 hours under an occlusive dressing, the skin was washed following dressing removal. There were no mortalities, and no abnormal clinical signs were noted during 14 day observation period, and all rats gained weight. There were no treatment-related findings at gross necropsy. The authors concluded that based on weight gain, survival and the absence of clinical signs, no signs of percutaneous absorption (leading to systemic toxicity) were evident. Based on the results obtained in this study, the acute dermal LD50of BEPD to rats is >2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Only study available for this endpoint

Additional information

Acute oral toxicity

2-butyl-2-ethylpropanediol (BEPD) was administered by gavage to groups of Sprague-Dawley rats (5/sex) at dose levels of 2.0, 3.2 and 5.0 g/kg bw. Animals were observed for 15 days. Death occurred at 2.0 g/kg bw (1 male), 3.2 g/kg bw (2 males and 5 females) and 5.0 g/kg bw (5 males and 4 females) within 1 -24 hours of dosing. Signs of toxicity (including piloerection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy, decreased respiratory rate, ptosis, pallor of extremities and prostration) were observed at all dose levels. One female dosed at 2.0 g/kg bw and one surviving female dosed at 5.0 g/kg bw had low bodyweight gain during the first week of the study. All other surviving rats gained bodyweight over the study period. Gross necropsy decedent and surviving rats revealed no macroscopic abnormalities. The acute oral LD50 of BEPD in the rat was found to be 2.9 (2.2 - 3.6) g/kg bw for males and females combined, under the conditions of this study.

Acute inhalation toxicity

Due to the physicochemical properties of the substance (it is not a volatile liquid or a fine powder), inhalation exposure is unlikely and no study is required.

Acute dermal toxicity

The acute dermal toxicity of BEPD was determined in a limit test with 5 male and 5 female CD(SD)BR VAF/Plus rats. The test substance was applied (after moistening with distilled water) to the shaved skin of the rats, in a single dose of 2000 mg/kg bw. The test substance was held in place for 24 hours under an occlusive dressing, the skin was washed following dressing removal. There were no mortalities, and no abnormal clinical signs were noted during 14 day observation period, and all rats gained weight. There were no treatment-related findings at gross necropsy. The authors concluded that based on weight gain, survival and the absence of clinical signs, no signs of percutaneous absorption (leading to systemic toxicity) were evident. Based on the results obtained in this study, the acute dermal LD50 of BEPD in rats is > 2000 mg/kg bw.

Justification for classification or non-classification

The data do not trigger classification of 2 -butyl-2 -ethylpropanediol for acute toxicity according to the CLP Regulation