Registration Dossier

Administrative data

Description of key information

The acute oral toxicity of the test substance, 4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with fatty acids, C18-unsatd., dimers, was accessed in two independent rat studies.  The test substance was evaluated in an O.E.C.D. test guideline no. 420 rat Acute oral study.   Acute dermal toxicity was evaluated in an independent rat 24 hr exposure study.    

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: The study was conducted according to the O.E.C.D. test guideline 420 with GLP compliance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All animals were dosed once only by gavage using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the time of dosing.
Doses:
Limit dose, 2000 mg/kg of body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
All animals were dosed once only by gavage at 2000 mg/kg of body weight. Deaths and overt signs of toxicity were recorded , 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded on the day of treatment (day 0) and on days 7 and 14, or at death. At the end of the study the animals were sacrificed and subjected to macroscopic examination. This consisted of opening the abdominal and examining all major organs. The macroscopic apperance of abnormal organs if present was recorded.
Statistics:
Not required.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
Hunched posture was noted during the day of dosing in the initial treated animal. There were no signs of systemic toxicity noted in the remaining animals.
Body weight:
Surviving animals showed expected gain in bodyweight during the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The acute oral median lethal dose (LD50) of the test material, 4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with fatty acids, C18-unsatd., dimers in the female Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

An O.E.C.D. test guideline no. 420 Fixed dose Acute Oral Toxicity Study in the rat was conducted at the Limit Dose of 2000 mg/kg of body weight of the test substance, 4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with fatty acids, C18-unsatd., dimers. The acute oral median lethal dose (LD50) of the test substance in the female Wistar strain rat is greater than 2000mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the O.E.C.D. test guideline 402 with GLP compliance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
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:
Five male and five female Wistar (RccHan™:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals weighed at least 200 g, and were eight to twelve weeks of age. The weight variation did not exceed ±20% of the mean weight for eachsex.
The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-Hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness. The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
On the day before treatment the back and flanks of each animal were clipped free of hair.
Using available information on the toxicity of the test item, a group of five male and five female rats was treated with the test item at a dose level of 2000 mg/kg.
The calculated volume of test item, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.
After the 24-Hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with DMSO followed by distilled water to remove any residual test item. The animals were returned to group housing for the remainder of the study period.
Duration of exposure:
24 hours
Doses:
2000 mg/Kg of body weight.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The calculated volume of test item, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage. The animals were caged individually for the 24-Hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

The animals were observed for deaths or overt signs of toxicity %, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31:
Statistics:
No data
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
None
Body weight:
Normal body weight gain.
Gross pathology:
No findings.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
No adverse findings were made in the study. The rat acute dermal LD50 for the test substance is > 2000 mg/Kg of body weight. The test substance is non-toxic by the dermal route of exposure in the rat.
Executive summary:

The test substance, 4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with fatty acids, C18-unsatd., dimers was evaluated for acute dermal toxicity in the rat by an O.E.C.D. test guideline no. 402 study.No adverse findings were made in the study. The rat acute dermal LD50 for the test substance is > 2000 mg/Kg of body weight. The test substance is non-toxic by the dermal route of exposure in the rat.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
mg/kg bw

Additional information

Based on a the rat acute oral toxicity of the test substance, 4,4'-Isopropylidenediphenol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with fatty acids, C18-unsatd., dimers is > 2000 mg/kg of body weight. The rat acute dermal LD50 was > 2000 mg/kg of body weight in a 24 hr exposure study. The rabbit acute dermal toxicity study also had a LD50 of > 2000 mg/Kg of body weight.

Justification for classification or non-classification

Based on the available study data, Classification for acute toxicity is not required.