Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Conducted in compliance with FDA and EPA good laboratory practices

Data source

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

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 10 male and 10 female Fischer 344 rats were exposed by inhalation to 0 or 170 mg/cubic meter Bisphenol A for 6 hours. The mass median aerodynamic diameter (MMAD) for the Bisphenol A aerosol was 3.9 µm (geometric standard deviation = 3.5). Body weights were obtained on the first day after exposure and approximately twice per week during a 14-day post-exposure period. Necropsies of 5 males and 5 females from each group were performed the day after exposure. All other rats were submitted for a gross necropsy examination at the end of the 14-day post-exposure period.
GLP compliance:
yes
Test type:
standard acute method

Test material

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

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7-9 weeks
- Housing: Animals were housed in groups in stainless steel cages during the acclimation period and were housed singly during exposure and the 14-day post-exposure period.
- Diet: Ad libitum (except during exposure). Certified Rodent Chow (Ralston Purina Co., St. Louis, Missouri, United States).
- Water: Ad libitum (except during exposure). Municipal tap water analysed by the City of Midland, Michigan, United States.
- Acclimation period: At least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature: 72 degrees F
- Humidity: 50%
- Photoperiod: 12 hours light/12 hours dark

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Polycarbonate grade BPA was aerosolised using a modified Marple dust generator. Approximately 90 liters/min of dry, compressed air was used to aerosolise the particles in the dust generator. The remaining air supplied to the chamber was controlled to maintain a temperature of 70 degrees F and relative humidity of 50%. The control chamber also had approximately 90 liters/min of dry, compressed air added to the chamber airstream. Whole-body exposures were conducted using stainless steel and glass 1000 liter Rochester-type chambers. The airflow was maintained at approximately 200 liters/min. Groups of animals were exposed to room air or 170 mg/cubic meter BPA for 6 hours.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
The mass concentration of aerosol present in the chamber was determined gravimetrically at least 3 times on pre-weighed Teflon (TE36) filters during the 6-hour exposure period. Particle size of BPA was determined aerodynamically twice during the exposure.
Duration of exposure:
6 h
Concentrations:
170 mg/cubic meter
No. of animals per sex per dose:
10 males and 10 females
Control animals:
yes
Details on study design:
Groups of 10 male and 10 female Fischer 344 rats were exposed by inhalation to 0 or 170 mg/cubic meter BPA (the highest attainable concentration)for 6 hours. The mass median aerodynamic diameter (MMAD) for the BPA aerosol was 3.9 µm (geometric standard deviation = 3.5). Body weights were obtained on the first day after exposure and approximately twice per week during a 14-day post-exposure period. Necropsies of 5 males and 5 females from each group were performed the day after exposure. All other rats were submitted for a gross necropsy examination at the end of the 14-day post-exposure period.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
other: reversible nasal inflammation; reversible ulceration of incisive ducts
Effect level:
170 mg/m³ air
Exp. duration:
6 h
Mortality:
There were no deaths during the exposure period or 14-day recovery period.
Body weight:
Body weight gains of males exposed to BPA were slightly decreased from control values on the day after exposure, but were comparable to control values within 3 days following exposure. Body weights of females were comparable to control values.
Gross pathology:
Soiling of the face and forelimb in males and females and soiling of the perineal region in females was observed one day after exposure.
Other findings:
Histopathological changes were observed in the anterior portion of the nasal tissue. Acute inflammation of the external nares and ulceration of the incisive ducts were observed one day after exposure, but these changes were reversible within the 14-day recovery period. No evidence for systemic toxicity was observed throughout the study.

Applicant's summary and conclusion

Conclusions:
Exposure of rats to 170 mg/cubic meter BPA resulted in inflammation in the anterior portion of the nose and ulceration in the incisive ducts. These changes were reversible within the 14-day recovery period. No evidence for systemic toxicity was observed throughout the study.
Executive summary:

Groups of 10 male and 10 female Fischer 344 rats were exposed by inhalation to 0 or 170 mg/cubic meter Bisphenol A (the highest attainable concentration) for 6 hours. The mass median aerodynamic diameter (MMAD) for the Bisphenol A aerosol was 3.9 µm (geometric standard deviation = 3.5). Body weights were obtained on the first day after exposure and approximately twice per week during a 14-day post-exposure period. Necropsies of 5 males and 5 females from each group were performed the day after exposure. All other rats were submitted for a gross necropsy examination at the end of the 14-day post-exposure period. There were no deaths during the exposure period or 14-day recovery period. Body weight gains of males exposed to Bisphenol A were slightly decreased from control values on the day after exposure, but were comparable to control values within 3 days following exposure. Body weights of females were comparable to control values. Soiling of the face and forelimb in males and females and soiling of the perineal region in females was observed one day after exposure. Acute inflammation of the external nares and ulceration of the incisive ducts were observed one day after exposure, but these changes were reversible within the 14-day recovery period. No evidence for systemic toxicity was observed throughout the study.