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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Conducted under OECD Guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6-10 weeks.
- Housing: Animals were housed in groups of 5 by sex in grid floor stainless steel cages.
- Diet: Ad libitum, with the exception of an overnight fast prior to dosing. Food was re-introduced 3-4 hours after treatment. SQC Rat and Mouse Maintenance Diet No. 1, Expanded (Special Diets Services, Ltd., Stepfield, Witham, Essex, England). Food was considered to not contain any contaminant at a level that might have affected the objectives or integrity of the study.
- Water: Water was provided at all times and dispensed from glass water bottles. Water was considered to not contain any contaminant at a level that might have affected the objectives or integrity of the study.
- Acclimation period: At least 3 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 19-25 degrees C
- Humidity: 40-70%
- Photoperiod: 12 hours light/12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 1% methylcellulose
Details on oral exposure:
Suspensions of BPA in 1% methylcellulose vehicle were administered once to each animal by oral gavage using a metal stomach tube attached to a disposable plastic syringe.
Doses:
5000 mg/kg and 2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
no
Details on study design:
A single oral dose of 5000 mg/kg BPA was administered by gavage to 5 male and 5 female Sprague Dawley rats after an overnight fast. At the request of the study sponsor, a second group of 10 animals (5 males, 5 females) was treated with a single oral dose of 2000 mg/kg. Animals were observed for overt signs of toxicity or behavioural changes at 1 and 4 hours after treatment and subsequently once daily for 14 days. Body weights were recorded on the day before treatment (day -1), the day of treatment (day 0), days 7 and 14, and at death. All animals were subjected to gross necropsy examination.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 2 000 - <= 5 000 mg/kg bw
Mortality:
At 2000 mg/kg BPA, no animals died.
At 5000 mg/kg BPA, 1 male and 5 females died within 1-2 days after treatment.
Clinical signs:
At 5000 mg/kg BPA, major signs of toxicity noted on the day of dosing were lethargy, prostration, hunched posture, and piloerection. Three surviving animals were prostrate on the morning of day 1 and were found dead at afternoon death check approximately 30 hours after dosing.
At 2000 mg/kg BPA, all animals were lethargic or prostrate on the day of dosing. Occasional signs of chromodacryorrhoea and salivation were noted on the day of dosing and on day 1.
Body weight:
All surviving animals showed gains in body weight at study termination.
Gross pathology:
Common findings at necropsy of animals that died during the study were associated with the liver and gastrointestinal tract. All animals necropsied at study termination were unremarkable.

Applicant's summary and conclusion

Conclusions:
The acute oral median lethal dose of BPA in the rat was confirmed to be in excess of 2000 mg/kg and was approximately 5000 mg/kg.
Executive summary:

A single oral dose of 5000 mg/kg BPA was administered by gavage to 5 male and 5 female Sprague Dawley rats after an overnight fast. At the request of the study sponsor, a second group of 10 animals (5 males, 5 females) was treated with a single oral dose of 2000 mg/kg. Animals were observed for overt signs of toxicity or behavioural changes at 1 and 4 hours after treatment and subsequently once daily for 14 days. Body weights were recorded on the day before treatment (day -1), the day of treatment, days 7 and 14, and at death. All animals were subjected to gross necropsy examination. At 5000 mg/kg BPA, 1 male and 5 females died within 1-2 days after treatment. Major signs of toxicity noted on the day of dosing were lethargy, prostration, hunched posture, and piloerection. Three surviving animals were prostrate on the morning of day 1 and were found dead at afternoon death check approximately 30 hours after dosing. At 2000 mg/kg BPA, no animals died, but all animals were lethargic or prostrate on the day of dosing. Occasional signs of chromodacryorrhoea and salivation were noted on the day of dosing and on day 1. All surviving animals from both dose groups showed gains in body weight at study termination. Common findings at necropsy of animals that died during the study were associated with the liver and gastrointestinal tract. All animals necropsied at study termination were unremarkable. The authors concluded that the acute oral median lethal dose of BPA in the rat was in excess of 2000 mg/kg and was approximately 5000 mg/kg.