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 425 with GLP compliance.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no

Test material

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

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Female animals were acquired from Texas Animal Specialties; Humble, Texas and weighed 159-184 grams on study day 0 (fasted). The animals were maintained in suspended stainless steel with wire bottom cages, 1 per cage. The set temperature range was 22° ± 3°C and relative humidity was set at 3 0-70%. A 12-hour light/dark cycle and 10-12 air changes/hour was maintained. The animals were allowed PMI Feeds lnc.TM Formulab #5008; ad libitum except for approximately 16 hours before dosing. Water was Sugar Land, Texas municipal water supply analyzed by TCEQ Water Utilities Division; available ad lib itum from automatic water system.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was administered as received and was not diluted. An individual dose was calculated for each animal based on its fasted body weight and administered by gavage at a volume ranging from 0.163 mL/kg at the 175 mg/kg level to 1.86 mL/kg at the 2000 mg/kg level. Each dose was administered using an appropriately sized syringe and stainless steel ball-tipped intubation needle. The animals were returned to their cages inimediately after dosing.
Doses:
175, 550 and 2000 mg/kg of body weight.
No. of animals per sex per dose:
175 mg/kg - one animal, 550 mg/kg - one animal, 2000 mg/kg - three animals
Control animals:
no
Details on study design:
Observations for mortality and clinical/behavioral signs of toxicity were made at least three times on the day of dosing (Day 0) and at least once daily thereafter for 14 days. Individual body weights were recorded just prior to dosing and on Days 7 and 14, or at the time of discovery after death. On Day 14 after dosing, each surviving animal was euthanized by an overdose of CO2. All study animals, whether dying during the study or euthanized, were subjected to gross necropsy and all abnormalities were recorded.
Statistics:
The LD50 value with 95% confidence interval was calculated using the A0T425 Stat Program supplied by the EPA.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal at 2000 mg/kg of body weight.
Clinical signs:
All surviving animals appeared normal for the duration of the study. Clinical signs in the animal that died on test included activity decrease, diarrhea, no defecation, piloerection and staggered gait.
Body weight:
Animals surviving to study termination exhibited normal weekly weight gain during the study.
Gross pathology:
The gross necropsy on the animal that died on test revealed crust around tail; discolored liver and contents in small intestine; and empty stomach/large intestine. The gross necropsy on animals surviving to termination of the study revealed no observable abnormalities.

Applicant's summary and conclusion

Interpretation of results:
relatively harmless
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The estimated LD50 for the test substance to female rats was 2000 mg/kg of body weight, and is therefore relatively nontoxic.
Executive summary:

The acute oral toxicity of the test substance, 4,4'-Isopropylidenedicyclohexanol, oligomeric reaction products with 1-chloro-2,3-epoxypropane, was estimated by an O.E.C.D. 425 test guideline GLP study conducted in female rats. The estimated LD50 for the test substance to female rats was 2000 mg/kg of body weight, and is therefore relatively nontoxic.