4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with biphenyl-4-ol

Endpoint summary

Description of key information

LD50(oral, rat): >2000 mg/kg body weight;
LD50(dermal, rat): >2000 mg/kg body weight

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:

February 7 to February 21, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline test with GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMAL MANAGEMENT
Equal numbers of healthy male and female CD rats of Sprague-Dawley origin (Hsd:Sprague- Dawley(CD)) were obtained from Harlan U.K. Ltd., Bicester, Oxon，England.
They were in the weight range of 96 to 116 g and approximately four to seven weeks of age prior to dosing (Day 1). All the rats were acclimatised to the experimental environment for a period of six days prior to the start of the study.
The rats were allocated without conscious bias to cages within the treatment groups. They were housed in groups of up to five rats of the same sex in metal cages with wire mesh floors in Building R14 Room 6.
A standard laboratory rodent diet (SDS LAD 1) and drinking water were provided ad libitum. Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
Each batch of diet used for the study was analysed for certain nutrients，possible contaminants and micro-organisms.
Results of routine physical and chemical examination of drinking water at source, as conducted, usually weekly by the supplier, are made available to Huntingdon Life Sciences Ltd. as quarterly summaries.
Animal room temperature was set to achieve a temperature of 22 土 3°C. Relative humidity was not controlled but was anticipated to be in the range 30 - 70% RH. Permanent daily recordings of these parameters were made and these are archived with other Department raw data. Any slight deviation in temperature and humidity that may have occurred was not considered to have affected the integrity or validity of the study. Air exchange was maintained at 10 to 15 air changes per hour and lighting controlled by means of a time switch to provide 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period.
Each animal was identified by cage number and ear punching. Each cage was identified by a coloured label displaying the dose level, study schedule number, animal mark and the initials of the Study Director and Home Office licensee.

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

A group of ten fasted rats (five males and five females) was given a single dose by oral gavage of the test substance, formulated in 1 % w/v aqueous methylcellulose and administered at a dose level of 2.0 g/kg bodyweight.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

All animals were killed and examined macroscopically on Day 15, the end of the observation period.
Mortality
Cages of rats were checked at least twice daily for any mortalities.
Clinical signs
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of four hours). On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). This latter observation was at approximately 16.30 hours on week days or 11.30 hours on Saturdays and Sundays. The nature and severity of the clinical signs and time were recorded at each observation.
All animals were observed for 14 days after dosing.
Bodyweight
The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
TERMINAL STUDIES Termination
All animals were killed on Day 15 by cervical dislocation.
Macroscopic jpathology
All animals were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscolpic appearance of all tissues was recorded.

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No treatment related effects were observed during the test.

Mortality:

There were no deaths.

Clinical signs:

other: Clinical signs of reaction to treatment were confined to piloerection，seen in all rats. Recovery was complete in all instances by Day 5.

Gross pathology:

No abnormalities were recorded at the macroscopic examination on Day 15.

Other findings:

No data

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of acute oral toxicity of test article to rats was found to be greater than 2000 mg/kg body weight under the conditions of this study.

Executive summary:

This study was performed to assess the acute oral toxicity of test article to the rat. The method followed was that described in OECD Guideline for Testing of Chemicals No. 401.

A group of ten fasted rats (five males and five females) was given a single dose by oral gavage of the test substance, formulated in 1%w/v aqueous methylcellulose and administered at a dose level of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day15，the end of the observation period.There were no deaths. Clinical signs of reaction to treatment were confined to piloerection，seen in all rats. Recovery was complete in all instances by Day 5.A slightly low bodyweight gain was recorded for one male on Day 15. All other rats achieved satisfactory bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15.

The acute lethal oral dose to rats of test article was found to be greater than 2.0 g/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

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

Study period:

February 12 to February 26, 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline test with GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMAL MANAGEMENT
Equal numbers of healthy male and female CD rats of Sprague-Dawley origin (Hsd:Sprague- Dawley(CD)) were obtained from Harlan U.K. Ltd., Bicester, Oxon, England.
They were in the weight range of 228 to 300 g and approximately seven to ten weeks of age prior to dosing (Day 1). Rats were acclimatised to the experimental environment for a minimum period of 25 days prior to the Start of the study.
The rats were allocated without conscious bias to cages within the treatment group. They were housed individually in meta1 cages with wire mesh floors in Building R14 Room 6.
A standard laboratory rodent diet (SDS LAD 1) and drinking water were provided ad libitum. Each batch of diet used for the study was analysed for certain nutrients, possible contaminants and micro-organisms.
Results of routine physical and chemical examination of drinking water at source as conducted, usually weekly by the supplier are made available to Huntingdon Life Sciences Ltd. as quarterly summaries.
Animal room temperature was Set to achieve a temperature of 22 ± 3°C. Relative humidity was not controlled but was anticipated to be in the range 30 - 70% RH. Permanent daily recordings of these Parameters were made and these are archived with other Department raw data. Any slight deviatiori
in temperature and humidity that may have occurred was not considered to have affected the integrity or validity of the study. Air exchange was maintained at 10 to 15 air changes per hour and lighting controlled by means of a time switch to provide 12 hours of artificial light (0700 - 1900 hours) in each 24-hour period.
Each animal was identified by cage number and ear punching. Each cage was identified by a coloured labe1 displaying the dose level, study schedule number, animal mark and the initials of the Study Director and Home Office licensee.

Type of coverage:

occlusive

Vehicle:

CMC (carboxymethyl cellulose)

Details on dermal exposure:

A group of ten rats (five males and five females) was treated at 2.0 g/kg bodyweight.
One day prior to treatment hair was removed from the dorso-lumbar region of each rat with electric clippers exposing an area equivalent to approximately 10% of the total body surface. The test substance was applied by spreading it evenly over the prepared skin. The treated area (approximately 50 mm X 50 mm) was then promptly covered with gauze which was held in place with a non- irritative dressing encircled firmly around the trunk.
At the end of the 24 hours exposure period, the dressings were carefully removed and the treated area of skin was washed with warm (30 to 40°C) water and blotted dry with absorbent Paper.
The day of dosing was designated Day 1 .

Duration of exposure:

24 hours

Doses:

2.0 g/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

TEST SUBSTANCE PREPARATION
BM1-Resin was formulated at a maximum practical concentration of 70% w/v in 1 % w/v aqueous methylcellulose and administered at a volume of 2.9 ml/kg bodyweight.
The test substance was prepared on the day of dosing. The absorption of the test substance was not determined. The homogeneity, stability and purity of the test substance were the responsibility of the Sponsor.
Mortality
Cages of rats were checked at least twice daily for any mortalities.
Clinicai signs
Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of four hours). On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). This latter observation was at approximately 16.30 hours on week days or 11.30 hours on Saturdays and Sundays. The nature and severity of the clinical signs and time were recorded at each observation. All animals were observed for 14 days after dosing.
Dermal responses
Local dermal irritation at the treatment site was assessed daily using the following numerical System:
Erythema and eschar formation:
No erythema 0
SI ight erythema 1
Well-defined erythema 2
Moderate erythema 3
Severe erythema @eet redness) to slight
eschar formation (injuries in depth) 4
Oedema formation:
No oedema 0
Slight oedema 1
Well-defined oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre
and extending beyond the area of exposure) 4
Bodyweight
Individual bodyweights were recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
Macroscopic examination
All animals were killed on Day 15 by cervical dislocation and were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all examined tissues was recorded.

Statistics:

no data

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No treat-related effects were observed during the test.

Mortality:

No death

Clinical signs:

other: There were no signs of systemic reaction to treatment. DERMAL RESPONSES Sites of application of BM1-Resin showed no irritation or other dermal changes (scores of zero for erythema and oedema were recorded for all animals).

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Other findings:

no data

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of acute dermal toxicity to rats was found to be greater than 2000 mg/kg body weight based on this results given in this report.

Executive summary:

This study was performed to assess the acute dermal toxicity of test article to the rat. The method followed was that described in OECD Guideline for Testing of Chemicals No. 402.

A group of ten rats (five males and five females) was given a single dermal application of the test substance, formulated at a maximum practical concentration of 70% w/v in 1 % w/v aqueous methylcellulose and administered at a dosage of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no deaths and no signs of systemic reaction to treatment. Sites of application of test article showed no irritation or other dermal changes. In comparison with historical data from the Department of Industrial Toxicology, a slightly low bodyweight gain was recorded for two males and two females on Day 8, with a similar trend noted for one male and two females on Day 15. All other rats achieved satisfactory bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15.

Therefore, the acute lethal dermal dose to rats of test substance was found to be greater than 2.0 g/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Due to low vapor pressure (<1.33E-8 Pa at 20 °C) and high boiling point (> 375 °C), the inhalation route is not considered to be a relevant exposure route to human. In addition, the data of acute toxicity by oral and dermal route is available and sufficient for assessment of acute toxicity of test article.Thus, the acute inhalation toxicity study can be waived.

oral:

One study(report no.OND 66/960426/AC) was performed to assess the acute oral toxicity of test article to the rat. The method followed was that described in OECD Guideline for Testing of Chemicals No. 401.

A group of ten fasted rats (five males and five females) was given a single dose by oral gavage of the test substance, formulated in 1%w/v aqueous methylcellulose and administered at a dose level of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day15，the end of the observation period.There were no deaths. Clinical signs of reaction to treatment were confined to piloerection，seen in all rats. Recovery was complete in all instances by Day 5.A slightly low bodyweight gain was recorded for one male on Day 15. All other rats achieved satisfactory bodyweight gains throughout the study.No abnormalities were recorded at the macroscopic examination on Day 15.

The acute lethal oral dose to rats of test article was found to be greater than 2.0 g/kg bodyweight.

dermal:

Another study(report no.OND 67/960549/AC ) was performed to assess the acute dermal toxicity of test article to the rat. The method followed was that described in OECD Guideline for Testing of Chemicals No. 402.

A group of ten rats (five males and five females) was given a single dermal application of the test substance, formulated at a maximum practical concentration of 70% w/v in 1 % w/v aqueous methylcellulose and administered at a dosage of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no deaths and no signs of systemic reaction to treatment. Sites of application of test article showed no irritation or other dermal changes. In comparison with historical data from the Department of Industrial Toxicology, a slightly low bodyweight gain was recorded for two males and two females on Day 8, with a similar trend noted for one male and two females on Day 15. All other rats achieved satisfactory bodyweight gains throughout the study. No abnormalities were recorded at the macroscopic examination on Day 15. The acute lethal dermal dose to rats of test substance was found to be greater than 2.0 g/kg bodyweight.

Therefore, test substance cannot cause acute toxicity based on the available data.

Justification for selection of acute toxicity – inhalation endpoint
Due to low vapor pressure (<1.33E-8 Pa at 20 °C) and high boiling point (> 375 °C), the inhalation route is not considered to be a relevant exposure route to human. In addition, the data of acute toxicity by oral and dermal route is available and sufficient for assessment of acute toxicity of test article.Thus, the acute inhalation toxicity study can be waived.

Justification for classification or non-classification

Based on the available data, test substance can not be classified for acute toxicity in accordance with CLP (Regulation EC No.1272/2008).