Registration Dossier

Administrative data

Description of key information

ORAL
An acute oral gavage study in male and female rats performed according to US EPA Toxic Substance Control Act (TSCA) Health Effects Test Guidelines indicated an LD50 of >5000 mg/kg-bw.
DERMAL
An acute dermal toxicity study in male and female rabbits performed according to US EPA TSCA Health Effects Test Guidelines indicated an LD50 of >2000 mg/kg-bw.

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: US EPA Toxic Substance Control Act (TSCA) Health Effects Test Guidelines (1982 and 1984)
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: US EPA Toxic Substance Control Act (TSCA) Health Effects Test Guidelines (1982 and 1984)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Doses:
5000 mg/kg
No. of animals per sex per dose:
5/sex
Details on study design:
An appropriate amount of the test substance was mixed with distilled water to give a 50% concentration. The resulting suspension was administered to five male and five female rats at a dose volume of 10 mL/kg which provided a dose of 5000 mg/kg of bisphenol dianhydride. The dose was administered by gavage through a commercial 16 gauge (3 inch) ball-end stainless steel needle attached to a disposable syringe. The rats were fasted from food overnight (approximately 18 hours) before dosing. The rats weighed between 200 and 250 g and were approximately 5 to 8 weeks of age at the time of dosing. Animals were observed for signs of toxic effects frequently on the day of dosing and twice daily thereafter for 14 days. Body weights were recorded on the day of dosing and at 7 and 14 days after dosing. A gross necropsy was performed on all animals 14 days after dosing.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
All animals survided to scheudled termination.
Clinical signs:
There were no signs of toxicity during the 14-day post-dosing observation period.
Body weight:
All rats gained weight during the 14-day post-dosing period.
Gross pathology:
There were no remarkable gross pathologic lesions found at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the oral rat LD50 of Bisphenol Dianhydride was determined to be >5000 mg/kg.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw
Quality of whole database:
The two studies provided are adequate to address this endpoint; therefore the quality of the database is considered to be good.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: US EPA Toxic Substance Control Act (TSCA) Health Effects Test Guidelines (1982 and 1984)
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: US EPA Toxic Substance Control Act (TSCA) Health Effects Test Guidelines (1982 and 1984)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
Ten rabbits (5/sex), weighing 2.0 to 3.0 kg and approximately 12 to 18 weeks of age were used on study.
Type of coverage:
occlusive
Details on dermal exposure:
The test substance was moistened with distilled water and applied to the dorsal surface of the clipped trunk of each rabbit. The coverage was approximately 43 mg of sample per cm2 of rabbit skin surface. A double layer of gauze sheeting was wrapped around the trunk and secured with adhesive tape. Polyethylene sheeting and bandaging tape were then wrapped around the trunk. Animals were returned to their cages. After 24 hours, all covering was removed and as much excess test material as possible was carefully removed.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5/sex
Control animals:
no
Details on study design:
Treated rabbits were observed frequently for signs of toxic effects on the first day of the test and twice daily thereafter for 14 days.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
All rabbits survived.
Clinical signs:
There were no signs of toxicity during the test.
Body weight:
All rabbits gained weight during the 14-day post-application period.
Gross pathology:
Gross pathologic evaluation revealed only a pitted surface of the kidneys of one male.
Other findings:
No local skin reactions were apparent.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 in rabbits is greater than 2000 mg/kg under the conditions of this study.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The two studies provided are adequate to address this endpoint; therefore the quality of the database is considered to be good.

Additional information

Oral Toxicity

In the key study, the acute oral toxicity potential of BPA-DA was determined in accordance with the US EPA Toxic Substance Control Act (TSCA) Health Effects Test Guidelines (Bushy Run Research Center, 1988).The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Male and female Sprague-Dawley rats (5/sex) were dosed with the test material in water via gavage at a limit dose of 5000 mg/kg.

Under the conditions of this study, the oral rat LD50 was determined to be >5000 mg/kg.

 

In the supporting study, the acute oral toxicity potential of BPA-DA was determined in a study conducted using methodology similar to that outlined in OECD 401 (International Research and Development Corporation, 1974).The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

Male Spartan (albino) rats (2/dose) were exposed to the test material at 500 and 5000 mg/kg in corn oil via gavage.

Under the conditions of this study, the male rat oral LD50 for Bisphenol Dianhydride was determined to be >5000 mg/kg.

Inhalation Toxicity

In accordance with section 8.5.2 of Column 2 of REACH Annex VIII, testing via the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

For BPA-DA, exposure via the inhalation route is unlikely due to the low vapour pressure (calculated to be 5E-18 Pa at 25 °C). Furthermore, as the substance is not marketed as such on the EU market, but as a monomer in a polymer only and the residual levels are below 0.1 %, the exposure and emissions to the environment are considered to be negligible. It is therefore considered justified to omit this study.

 

Dermal Toxicity

In the key study, the acute dermal toxicity potential of BPA-DA was determined in accordance with the US EPA Toxic Substance Control Act (TSCA) Health Effects Test Guidelines (Bushy Run Research Center, 1988).The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Male and female New Zealand White rabbits (5/sex) were dosed with the test material at a limit dose of 2000 mg/kg in an occlusive fashion for 24 hours.

Under the conditions of this study, the acute dermal LD50 in rabbits is greater than 2000 mg/kg.

 

In the supporting study, the acute dermal toxicity potential of BPA-DA was determined in a study conducted using methodology similar to that outlined in OECD 402 (International Research and Development Corporation, 1974).The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

Male and female New Zealand White rabbits (1/sex/dose) were exposed to the test material at 200 and 2000 mg/kg in an occlusive fashion for 24 hours.

Under the conditions of this study, the acute dermal LD50 in rabbits is greater than 2000 mg/kg.


Justification for selection of acute toxicity – oral endpoint
Two studies in the rat are available to address this endpoint. The key study was selected on the basis that it was conducted in accordance with the US EPA standardised guidelines and was considered to be more reliable; the supporting study was conducted using methodology similar to that outlined in the standardised guideline OECD 401 but only examined 2 animals per dose group.

Justification for selection of acute toxicity – dermal endpoint
Two studies in the rabbit are available to address this endpoint. The key study was selected on the basis that it was conducted in accordance with the US EPA standardised guidelines and was considered to be more reliable; the supporting study was conducted using methodology similar to that outlined in the standardised guideline OECD 402 but only examined 2 animals per dose group.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute toxicity via the oral and dermal routes.