Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1994
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
no
GLP compliance:
no
Remarks:
The study was conducted prior to the creation of the REACH regulation. The study was well documented and is sufficient for classification.
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: The test material was stored frozen.

FORM AS APPLIED IN THE TEST (if different from that of starting material): The test material was thawed and administered undiluted

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc. Portage, MI
- Weight at study initiation: approximately 264 g (males) and 243 g (females)
- Fasting period before study: Fasted overnight prior to test material administration
- Housing: Housed in group cages (by sex) in temperature and humidity controlled quarters
- Diet (e.g. ad libitum): ad libitum; Laboratory Rodent Diet #5001, Purina Mills, Inc
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 7 days

IN-LIFE DATES: From: 25 February 1994 To: 22 April 1994

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The undiluted test material was brought to room temperature and administered by gavage using a bulk density determination of 1.11 g/mL to determine the dose volume for each dose level. An individual dose was calculated for each animal based on its fasted body weight.
Doses:
500 and 5000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical obervations and mortality checks at 1, 2.5, and 4 hours after test material administration. Additional clinical observations and twice daily mortality checks (morning and afternoon) were conducted daily thereafter for 14 days. Body weights were determined before test material administration (Day 0), at Day 7, and at termination of the experimental phase (Day 14).
- Necropsy of survivors performed: yes
Statistics:
No statistical analyses were required by the protocol.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 500 - < 5 000 mg/kg bw
Based on:
test mat.
Mortality:
All mortality occurred within 5 days of administration of the test material; 2 of 5 female (day 1 and 5) and none of 5 males died at the 500 mg dose while 5 of 5 females and 5 of 5 males died at the 5 g dose between 2.5 hours and 1 day after administration of the test material.
Clinical signs:
Clinical signs of toxicity included excessive salivation, red-stained face, miosis, thin appearance, hypoactivity, lacrimation, soft stool, yellow-stained urogenital area, staggered gait, squinting eyes, dyspnea, absence of rightly/grasping reflex, gasping and death. All surviving animals returned to a normal appearance by day 6 after treatment.
Body weight:
There was no meaningful effect on body weight gain in surviving animals.
Gross pathology:
There were no visible lesions in any of the animals.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results of the study, the test article has a rat oral LD50 between 500 and 5000 mg/kg body weight.
Executive summary:

Two groups of ten albino rats (Sprague-Dawley strain, five males, five females) weighing between 228 and 273 grams received an oral dose of the test article equivalent to either 500 mg (0.45 mL) or to 5000 mg (4.50 mL) per kilogram of body weight. This study was conducted according to OECD 401 (1981). Clinical signs of toxicity included excessive salivation, red-stained face, miosis, thin appearance, hypoactivity, lacrimation, soft stool, yellow-stained urogenital area, staggered gait, squinting eyes, dyspnea, absence of rightly/grasping reflex, gasping and death. All mortality occurred within 5 days of administration of the test material; 2 of 5 female and none of 5 males died at the 500 mg dose while 5 of 5 females and 5 of 5 males died at the 5 g dose between 2.5 hours and 1 day after administration of the test material. All surviving animals returned to a normal appearance by day 6 after treatment. There was no meaningful effect on body weight gain in surviving animals. The gross necropsy at termination revealed no visible lesions in any test animals.  Based on the results of the study, the test article has a rat oral LD50 between 500 and 5000 mg/kg body weight.