4,4'-Isopropylidenediphenol, ethoxylated

Endpoint summary

Description of key information

In both the acute toxicity: oral and the acute toxicity: dermal studies the LD50 was >2000 mg/kg bw. The inhalation toxicity study demonstrated that, under the test conditions and at the maximum achievable test concentrations, the substance vapours were not toxic.

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

Study period:

From 30 NOV 2011 to 31 MAY 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

December 17, 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December, 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Test species/strain/quality: Rat/Wistar/Crl:WI (Han)
Reason for selection of the test species: Rats were selected since this rodent species is recommended in the respective test guidelines. Wistar rats were selected since there is extensive experience available in the laboratory with this strain of rats.
Age on day 0: Young adult animals (female animals approx. 10 weeks)
Sex: As suggested by the OECD guideline nulliparous and non-pregnant female animals were used for the test, because there is no indication that male animals are likely to be more sensitive to the acute effects of the test item.
Supplier: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfed, Germany.
Arrival in the testing facility: Acclimatization period of at least 5 days before the beginning of the experimental phase: during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.
Identification: Individual identification by cage cards and tail marking.
Body weight on day 0: Animals of comparable weight (+/- 20% of the mean weight)
Room temperature/relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 22°C ± 3°C for temperature and of 30-70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Route of administration: Single oral administration by gavage
Fasting period: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
Time of day of administration: In the morning
Observation period: 14 days

Doses:

2000 mg/kg/bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

By request of the sponsor a starting dose of 2000 mg/kg/bw was chosen in the first step with 3 female animals. Because no mortality occurred in the first step, 2000 mg/kg/bw were administered to another group of 3 females animals in the second step.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were observed during clinical examination.

Gross pathology:

There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral median lethal dose (LD50) of the test material was found to be > 2000 mg/kg bodyweight. The classification of test substance for acute oral toxicity is not warranted in accordance with CLP Regulation 1272/2008.

Executive summary:

In an acute oral toxicity study (acute toxic class method, according to OECD Test Guideline 423), groups of approx. 10 weeks old female rats (n= 3 rats/step) were given a single oral dose of the undiluted test material (purity: 99.2%). In the first step, three females received 2000 mg/kg bw, and all animals treated with this dose survived until the end of the study without showing any test item-related signs of toxicity. Based on these results and according to the acute toxic class method regime, a second step was performed at a dose of 2000 mg/kg bw. All animals survived; throughout the 14-day observation period, they did not show any test item related signs of toxicity. Necropsy of the surviving rats did not reveal any findings. Based on the results from this study, the oral LD50 is considered to be > 2000 mg/kg bw. Therefore, the classification of test substance for acute oral toxicity is not warranted in accordance with CLP Regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Four studies were conducted to assess the acute oral toxicity of the substance. All studies were considered reliable as they were conducted on the registered substance, as defined in section 1.1.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(Inhalation hazard test described in the Annex V; adopted 1981)

Deviations:

yes

Remarks:

observation period of 7 days

Principles of method if other than guideline:

Standardized test method (BASF-Test): The test was performed in principle as described in OECD test guideline 403. It demonstrates the toxicity of an atmosphere saturated with vapours of the volatile components of a test substance at 20°C. Young adult laboratory rats, 3 per sex, were exposed sequentially to the vapours generated by bubbling 200 L/h air through a substance column of about 5 cm above a fritted glass disc in a glass cylinder for 8 h. The exposure was subsequently repeated in the same manner. No analytical determination of the atmosphere concentrations was performed. The nominal concentration was calculated as quotient of the amount of test substance weight loss during exposure, and the amount of air used during exposure. Group-wise documentation of clinical signs was performed over a 7 day study period. Body weight of groups was determined before the start of the study and at the end of the observation period.

GLP compliance:

no

Test type:

other: inhalation risk test

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION

Rats were exposed for 8 h to a vapour saturated atmosphere. Vapour was generated by bubbling 200 l/h air through the liquid substance column (volume ca. 50 mL) of about 5 cm above a fritted glass disc in a glass cylinder. The air pressure was 754 mm Hg. Temperature in the exposure chamber was 20°C. Concentration was stated in the raw data to be 0.021 mg/L in the case of the 8 h exposure.

TEST ATMOSPHERE

Brief description of analytical method used: no analytics performed
Samples taken from breathing zone: no

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

8 h

Concentrations:

No verification of the concentration was performed. Nominal concentration: 0.021 mg/L

No. of animals per sex per dose:

2

Control animals:

no

Details on study design:

Duration of observation period following administration: 7 days
Frequency of observations and weighing: group wise documentation on working days
Necropsy of survivors performed: yes
Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

other: IHT

Effect level:

0.021 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

8 h

Remarks on result:

other: No mortality.

Mortality:

No mortality observed.

Clinical signs:

other:

Gross pathology:

No abnormality detected.

Interpretation of results:

study cannot be used for classification

Conclusions:

The IHT was given as 0.021 mg/L (air). No deaths or abnormalities were recorded. The substance vapours were not toxic at the maximum achievable test concentrations.

Executive summary:

The acute inhalation toxicity of the test substance to rats (strain not specified) was determined in an assay equivalent to the OECD Guideline for Testing of Chemicals 403. The rat was exposed to a whole body dose, nominally stated as 0.021 mg/L. The IHT was given as 0.021 mg/L (air). The animals were observed for 7 days. No deaths or abnormalities were recorded. The substance vapours were not toxic at the maximum achievable test concentrations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

Study period:

FROM 31 OCT 2011 to 31 MAY 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

February 24, 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

August, 1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nosan No. 8147

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test species/strain/quality: Rat/Wistar/Crl:WI (Han) SPF
Reasons for selection: Rats were selected since this rodent species is recommended in the respective test guidelines. Wistar rats were selected since there is extensive experience available in the laboratory with this strain of rats.
Age on day 0: Young adult animals. (Male animals approx. 8 weeks, females approx. 12 weeks)
Sex: Males and females
Supplier: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
Arrival in the testing facility: Acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet.
Identification: Individual identification by cage cards and tail marking.
Body weight on day 0: Animals of comparable weight.

Room temperature / relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 22°C ± 3°C for temperature and of 30 – 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.
Day/night rhythm: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of cage: Makrolon cage, type III
Number of animals per cage: Single housing
Feeding: VFR1(P); SDS Special Diets Services, 67122 Altrip, Germany
Drinking water: Tap water ad libitum

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

The undiluted test item was applied to clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by a semi-occlusive dressing.

TEST SITE
- Area of exposure: About 40 cm2
- % coverage: at least 10% of the body surface

REMOVAL OF TEST SUBSTANCE
Route of application: Single application to the clipped epidermis (dorsal and dorsolateral parts of the trunk); covering of the application site with a semi- occlusive dressing* for 24 hours. Afterwards removal of the semi- occlusive dressing, rinsing of the application site with warm water

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.73 mL/kg bw (for more details see 'Any other information on materials and methods incl. tables' section below)

Duration of exposure:

24 hours.

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
- Examinations and frequency:
Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
Clinical observations: Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.
Mortality: A check for any dead or moribund animals was made at least once each workday, these records are archived by Bioassay.
Pathology: Necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured.

Clinical signs:

other: No systemic clinical signs or local effects were observed during clinical examination.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Other findings:

No local effects observed

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw. According to EU CLP Regulation 1272/2008 criteria, the test substance is not classified for acute dermal toxicity.

Executive summary:

In the acute dermal toxicity study (according to OECD TG 402, Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item (purity: 99.2%) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred during the study and no signs of systemic toxicity or skin effects were observed in the animal. The mean body weight of the male animals increased throughout the study period within the normal range, the mean body weights of the female animals stagnated during the first post-exposure observation week probably due to the bandage procedure but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. The acute dermal median lethal dose (LD₅₀) was determined to be > 2000 mg/kg bw. Therefore, according to EU CLP Regulation 1272/2008 criteria, the test substance is not considered to be classified for acute dermal toxicity.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

Guideline study

Additional information

Two studies were conducted to assess the acute oral toxicity of the test material. These studies were considered reliable as they were conducted on the registered substance according to OECD Testing Guideline 401 and 423. Both studies gave an LD₅₀ > 2000 mg/kg bw on, the key study was on BPA 1 -4.5EO and the supporting study was on BPA 2EO. The registered substance is not classified as an acute oral toxin based on the EU Classification, Labelling and Packaging (CLP) criteria.

 

The acute toxicity: inhalation was assessed on the registered substance according to OECD Testing Guideline 403. The IHT was given as 0.021 mg/L (air). The substance vapours were not considered toxic at the maximum achievable test concentrations.

 

The acute toxicity: dermal of the registered substance was assessed according to OECD Testing Guideline 402. The LD₅₀ was > 2000 mg/kg bw on BPA 1 -4.5EO.

 

Based on the LD₅₀ values obtained from these studies, the registered substance is not classified as acutely toxic via the oral, inhalation or dermal route based on the EU Classification, Labelling and Packaging (CLP) criteria.

Justification for classification or non-classification

Based on the available data, BPA EO does not warrant classification for acute toxicity according to the CLP Regulation (EC) No 1272/2008.