Registration Dossier

Diss Factsheets

Administrative data

Description of key information

LD50 oral rat below 2000 mg/kg bw

LD50 dermal rat below 2000 mg/kg

Acute inhalation toxicity via read-across Bisphenol A: 170 mg/m3 (highest attainable concentration, 6 h exposure) did not show systemic effects but local effects of irritation appeared

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: GLP compliant study comparable to guideline study
Principles of method if other than guideline:
according to Richtlinie 84/449/EWG (Amtsblatt der Europäischen Gemeinschaften Nr. L 251 vom 19.09.1984, S. 96); original language: German
GLP compliance:
yes
Test type:
other: similar to acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann, Borchen, Germany
- Age at study initiation: 7-9 weeks
- Weight at study initiation: mean males 172g, mean females 161g
- Fasting period before study: approximately 16 hours
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
- test substance was formulated at room temperature under stirring on a magnetic stirrer
- application volume was 10 ml/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: at least once daily for clinical signs and mortality
- Frequency of weighing: before adminstration, after one week and et the end of the 14-day observation period
- Necropsy of survivors performed: yes
Statistics:
not adequate for limit test
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: clinical signs: slight piloerection confined to the first 4 hours after application
Mortality:
none
Clinical signs:
other: slight piloerection confined to the first 4 hours after treatment; no further observations
Gross pathology:
no effects
Conclusions:
LD50 was estimated to be greater than 2000 mg/kg bw
Executive summary:

The acute oral toxicity of the test item was evaluated in a GLP-compliant study on male and female Wistar rats. The oral dose of 2000 mg/kg bw was tolerated without mortalities, effects on weight gain or gross pathological findings. Clinical signs were confined to slight piloerection within the first 4 hours after treatment. The LD50 of the test item can therefore be determined with > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
The registered UVCB substance 2-acetone, condensation product with phenol mainly, in the following referred to as UVCB substance, consists of 4,4’-isopropylidenediphenol (Bisphenol A, CAS-No. 80-05-7, typical concentration about 40%). Consequently, 4,4’isopropylidenediphenol has major influence on the potential of 2-acetone, condensation product with phenol with regard to human health effects. .

For the assessment of human health toxicity of the UVCB substance two approaches were followed:
1) Data generation for the UVCB substance itself and toxicological assessment on the basis of the gained results, supplemented with
2) Read-across based on toxicological data for the main component of the UVCB substance, i.e. 4,4’-isopropylidenediphenol (Bisphenol A, CAS-No. 80-05-7).

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Source: 4,4’-isopropylidenediphenol (EC No. 201-254-8)
Target: 2-acetone, condensation product with phenol (EC No. 931-252-8), consisting of about 40% 4,4’-isopropylidenediphenol

A separate document is attached for the description of the approach, called Information on Read-Across and DNEL Derivation for REACH Registration of 2-acetone, condensation product with phenol (EC Inventory No. 931-252-8)
Reason / purpose for cross-reference:
reference to other study
Sex:
male/female
Dose descriptor:
other: reversible nasal inflammation; reversible ulceration of incisive ducts
Effect level:
170 mg/m³ air
Based on:
test mat.
Exp. duration:
6 h
Conclusions:
Exposure of 10 male and 10 female Fischer 344 rats to 170 mg/m³ 4,4’isopropylidenediphenol (Bisphenol A) resulted in inflammation in the anterior portion of the nose and ulceration in the incisive ducts one day after exposure. These changes were reversible within the 14-day recovery period. No evidence for systemic toxicity was observed throughout the study. Since Bisphenol A is the main constituent (typical concentration about 40%) of the registered substance this result is considered as relevant for the registered substance.
Executive summary:

Exposure of 10 male and 10 female Fischer 344 rats to 170 mg/m³ 4,4’isopropylidenediphenol (Bisphenol A) resulted in inflammation in the anterior portion of the nose and ulceration in the incisive ducts one day after exposure. These changes were reversible within the 14-day recovery period. No evidence for systemic toxicity was observed throughout the study. Since Bisphenol A is the main constituent (typical concentration about 40%) of the registered substance this result is considered as relevant for the registered substance.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
170 mg/m³ air

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: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Strain: HsdCpb: Wu
- Source: Harlan GmbH, 5960 AD Horst, Netherlands
- Age at study initiation: approximately 9-13 weeks
- Diet and water: ad libitum
- Acclimation period: at least 5 days
Type of coverage:
other: semiocclusive, but predominantly covered with air-tight plaster
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TREATMENT
Test substance was applied ground by mortar on a wet gauze layer.
Treatment area: 30 cm²
TEST SITE
One day before the start of the treatment the back and flanks of the rats were shorn (approximately 10% of the body surface area). For each dose and animal the required amount of the pure liquid test substance was calculated on the base of the body weight at time of dosing. This amount was weighed and applied as uniformly and thinly as possible to the test area, covered with a gauze-layer (6.0 cm x 5.0 cm = 30.0 cm²) of a "Cutiplast steril" coated with air-tight "Leukoflex". The gauze strip was placed on the rat's back and secured with a "Lomir biomedical Inc rat jacket", which was connected with a safety pin to the stretch tape to ensure that the animals could not ingest the test substance.

REMOVAL OF TEST SUBSTANCE
After approximately 24 hours the dressings were removed and the area was rinsed with tepid water using soap and gently patting the area dry.
Duration of exposure:
24 hours
Doses:
limit dose of 2000 mg/kg bw ; according to 19.3 to 19.7 mg/cm² for male rats and 15.6 to 16.8 mg/cm² for female rats.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: at least 14 days
- Frequency of observations and weighing: once daily
- Necropsy of survivors performed: yes
Statistics:
none; limit dose test
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: signs of local irritation. partial reddening, indurations, encrustation and formation of scale at the treatment area
Mortality:
No mortalities occured.
Clinical signs:
other: Partial reddening of the skin, indurations, encrustation and formation of scale at the treatment area in all animals.
Gross pathology:
The necropsies performed at the end of the study revealed no particular findings.
Interpretation of results:
other: low toxicity
Executive summary:

An acute dermal toxicity study was performed on rats according to OECD TG 402. For the purpose of a limit test 2000 mg/kg bw of the test item were applied to the skin of 5 male and 5 female rats for 24 hours. Clinical signs were confined to signs of local irritation, as partial reddening of the skin, indurations, encrustation and formation of scale at the treatment area of all animals. The resulting LD50 was determined with > 2000 mg/kg bw for both sexes.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

The acute oral toxicity of the test substance was evaluated in a GLP-compliant study on male and female Wistar rats (Bomhard, 1990). The oral dose of 2000 mg/kg bw was tolerated without mortalities, effects on weight gain or gross pathological findings. Clinical signs were confined to slight piloerection within the first 4 hours after treatment. The LD50 of the test substance can therefore be determined with > 2000 mg/kg bw. This result was confirmed by a non-GLP compliant study, performed according to OECD TG 423 (Stropp, 1999).

There is no acute inhalation toxicity study available for the substance. However, based on read-across with acute toxicity data for 4,4’isopropylidenediphenol (Bisphenol A), the main constituent of the registered substance, the substance can be considered as not toxic after inhalative exposure but as irritating to the respiratory tract. Exposure of 10 male and 10 female Fischer 344 rats to 170 mg/m³ Bisphenol A (highest attainable concentration) resulted in inflammation in the anterior portion of the nose and ulceration in the incisive ducts one day after exposure. These changes were reversible within the 14-day recovery period. No evidence for systemic toxicity was observed throughout the study. Since Bisphenol A is the main constituent (typical concentration about 40%) of the registered substance this result is considered as relevant for the registered substance.

An acute dermal toxicity study was performed on rats according to OECD TG 402 (Gillissen, 2010). For the purpose of a limit test 2000 mg/kg bw of the test substance were applied to the skin of 5 male and 5 female rats for 24 hours. Clinical signs were confined to signs of local irritation, as partial reddening of the skin, indurations, encrustation and formation of scale at the treatment area of all animals. The resulting LD50 was determined with > 2000 mg/kg bw for both sexes.

Justification for classification or non-classification

No classification is required for acute oral and dermal toxicity based on the study results with the substance.

No data are available for acute inhalation toxicity of the substance. Based on read-across with 4,4’isopropylidenediphenol (Bisphenol A), the main constituent of the registered substance, the substance can be considered as not toxic after inhalative exposure but as irritating to the respiratory tract (STOT SE 3).