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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Test material form:
liquid: viscous

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Animals were received from Charles River (Raleigh, NC, and Stone Ridge, NY) on 23 Mar 2017 and
13 Apr 2017. Following an acclimation period of at least five days, three male and six healthy,
non-pregnant and nulliparous female Sprague Dawley rats were assigned to treatment groups without
conscious bias.
The animals were born on 25 Jan 2017, 01 Feb 2017, and 15 Feb 2017. The pretest body weight range
was 394 - 427 grams for males and 198 - 219 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.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test article was used as received and the dose was based on the sample weight as calculated from the specific gravity. A single dose was administered orally by syringe and dosing needle.
Doses:
300 - 2000 mg/kg b.w.
No. of animals per sex per dose:
Dose level of 2000 mg/kg was administered to three female rats. A dose level of 300 mg/kg was administered to two female and three male rats. One female rat received a dose level of 305 mg/kg.
Control animals:
no
Details on study design:
Type and Frequency of Observations
In Vivo - Animals 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. One female rat in the 300 mg/kg
dose group was also weighed on Day 5.
Post Mortem – All animals were humanely sacrificed using CO2 and were examined for gross pathology
following study termination.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Two females were found dead and one female rat was euthanized due to moribund condition by Day 1 following the single 2000 mg/kg oral dose.
Two female and three male rats survived following a single 300 mg/kg oral dose. One female rat survived following a single 305 mg/kg oral dose.
Clinical signs:
2000 mg/kg - Abnormal physical signs including wetness and red staining of the nose/mouth area, diarrhea, soiling and wetness of the anogenital area, piloerection, negative righting reflex, sagging eyelids, and tremors were observed.
300 mg/kg - Abnormal physical signs including wetness and brown staining of the nose/mouth area, piloerection, dyspnea, hunched posture, wetness and yellow staining of the anogenital area, chromorhinorrhea, ataxia, emaciation, unkempt appearance and localized hair loss were observed.
Body weight:
2000 mg/kg - Terminal body weight loss was observed among all three animals.
300 mg/kg - All six animals gained body weight by study termination; one animal lost weight from pre-test to Day 5.
Gross pathology:
2000 mg/kg - The gross necropsy revealed red staining on the nose/mouth area, yellow staining and soiling on the anogenital area, pale areas and darker than normal liver, darker than normal spleen, lighter than normal kidneys, and abnormalities of the gastrointestinal tract.
300 mg/kg - The gross necropsy revealed no observable abnormalities.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 of Isophoronediamine-cresyl glycidyl ether adduct is greater than 300 mg/kg but less than 2000 mg/kg of body weight in rats and is considered to be in GHS Category 4.
Executive summary:

The oral LD50 of Isophoronediamine-cresyl glycidyl ether adduct is greater than 300 mg/kg but less than 2000 mg/kg of body weight in rats and is considered to be in GHS Category 4.