Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Ethyl butyl propanediol
- Physical state: colourless crystalline powder
- Analytical purity: 98.2%

Test animals

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.

Administration / exposure

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).

Results and discussion

Preliminary study:
Dose levels were based on the results of a range finding study performed at 1.0 and 4.0 g/kg bw.
Effect levelsopen allclose all
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

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.