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Description of key information

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:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
01 Aug 2017, 17 Aug 2017, 22 Aug 2017. Following an acclimation period of at least five days, three
male and nine healthy, non-pregnant and nulliparous female Sprague Dawley rats were assigned to
treatment groups without conscious bias.
The male animals were born on 04 Jul 2017 and the female animals were born on 15 May 2017,
05 Jun 2017 and/or 21 Jun 2017. The pretest body weight range was 307 - 312 grams for males and
178 - 212 grams for females. The weight variation of the animals used did not exceed ±20% of the mean
body weight of the previously dosed animals within a sex.
The animals were identified by cage notation and indelible body marks, and housed in suspended wire
cages; five per sex per cage prior to dosing and three per sex per cage following dosing. Absorbent
paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rat
Chow (Diet No. 5012) was freely available except for 16-20 hours prior to dosing. Water was available ad
libitum. The animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a
12-hour light/dark cycle, and was kept clean and vermin free.
Route of administration:
oral: gavage
Vehicle:
ethanol
Details on oral exposure:
The test article was heated to a liquid state and formulated with a a vehicle to make administration via oral gavage feasible. A single dose was administered orally by syringe and dosing needle
Doses:
300-1000-2000 mg/kg
No. of animals per sex per dose:
2000 mg/kg - 3 female
1000 mg/kg - 3 female
300 mg/kg - 3 female + 3 male
Control animals:
no
Details on study design:
Initially, three healthy female Sprague Dawley rats were dosed orally with
DEAPA/AEP Epoxy Resin Adduct Lot# 735382-176-1 at 2000 mg/kg. Since all three animals died at this
level, additional animals were dosed as per the chart below. The rats were observed at 15 minutes,
1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects, and twice
daily for mortality. Body weights were recorded immediately pretest, weekly, at death and at termination
in the survivors. All animals were examined for gross pathology. The test article was assigned to a toxic
category based on the mortality response noted.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 300 - < 1 000 mg/kg bw
Based on:
test mat.
Mortality:
2000 mg/kg
Three females rat died within two hours following a single 2000 mg/kg oral dose.
1000 mg/kg
Three female rats died by Day 1 following a single 1000 mg/kg oral dose.
300 mg/kg
Three female and three male rats survived following a single 300 mg/kg oral dose.
Clinical signs:
2000 mg/kg
Prior to death, abnormal physical signs including diarrhea, ataxia, wetness of the nose/mouth area,
prostration, negative righting reflex, and tremors were observed.
1000 mg/kg
Prior to death, abnormal physical signs including wetness and brown staining of the nose/mouth area,
piloerection, dyspnea, lethargy, sagging eye lids, comatose, diarrhea, tremors, soiling of the
anogenital area, and chromodacryorrhea were observed.
300 mg/kg
Abnormal physical signs including wetness and brown staining of the nose/mouth area and
chromorhinorrhea were observed.
Body weight:
2000 mg/kg
One animal lost weight, one animal gained weight and one animal’s weight remained the same.
1000 mg/kg
Terminal body weight loss was observed among all three animals.
300 mg/kg
All six animals gained body weight by study termination.
Gross pathology:
2000 mg/kg
The gross necropsy revealed wetness of the nose/mouth area and abnormalities of the
gastrointestinal tract.
1000 mg/kg
The gross necropsy revealed red staining of the nose/mouth area and front legs, wetness and soiling
of the anogenital area, dark areas on the liver, and abnormalities of the gastrointestinal tract.
300 mg/kg
The gross necropsy revealed no observable abnormalities.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 of 4,4’-Isopropylidenediphenyl, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with cyclohex-1,2-ylenediamine is greater than 300 mg/kg but less than 1000 mg/kg of body weight in rats and considered to be in GHS Category 4.
Executive summary:

The oral LD50 of 4,4’-Isopropylidenediphenyl, oligomeric reaction products with 1-chloro-2,3-epoxypropane, reaction products with cyclohex-1,2-ylenediamine is greater than 300 mg/kg but less than 1000 mg/kg of body weight in rats and considered to be in GHS Category 4.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw

Additional information

Justification for classification or non-classification