Registration Dossier

Administrative data

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.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
As per IUCLID Sections 1.1. 1.2. and 4.1.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals 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.

Administration / exposure

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.

Results and discussion

Effect levels
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.

Applicant's summary and conclusion

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.