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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: comparable to guideline study with acceptable restriction

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Four groups each of 10 male rats and one group of 20 male rats were treated with the undiluted substance. The application volume was 17.8 mL/kg, 23.7 mL/kg, 27.4 mL/kg and 31.6 mL/kg, respectively. One control group with 10 male rats was treated with demineralized water at 31.6 mL/kg.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Alkyl (C12-C14) glycidyl ether
Label: Epoxide 8
51% C12 Glycidyl ether
21% C14 Glycidyl ether
5% C16 Glycidyl ether
13% N +1's
4% alpha addition Products
94% total active (label claim)
- Physical state: Clear colorless liquid
- Storage condition of test material: ambient

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Willi Gassner (WIGA) SPF breeding CH-8741 Sulzfeld Switzerland
- Weight at study initiation: between 110 g and 178 g (mean 133 g)
- Fasting period before study: overnight
- Housing: in groups of 10 or 20 animals in Makrolon (55x33x20) cages during acclimatization and in groups of 5 animals in Makrolon cages (38x22x15) after treatment and during observation.
- Diet: ad libitum except overnight before treatment
- Water: ad libitum
- Acclimation period: 3 to 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): approx. 22°C
- Humidity (%): approx. 57%



Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 31.6 mL /kg
Doses:
control group: 31.6 mL/ kg demineralized water
Test group 1: 17.8 mL/kg
Test group 2: 23.7 mL/kg
Test group 3: 27.4 mL/kg
Test group 4: 31.6 mL/kg
No. of animals per sex per dose:
Control group: 10 males
Test group 1: 10 males
Test group 2: 10 males
Test group 3: 10 males
Test group 4: 20 males
Control animals:
yes
Details on study design:
Four groups each of 10 male rats and one group of 20 male rats were treated with the undiluted substance. The single-application volume was 17.8 mL/kg, 23.7 mL/kg, 27.4 mL/kg and 31.6 mL/kg, respectively. One control group with 10 male rats was treated with demineralized water at 31.6 mL/kg.
All animals were examined for mortality and clinical signs at 10, 18 and 33 minutes, 1, 1.8, 3.3, 6 and 24 hours after treatment and at least once daily up to day 14, the end of the observation period. Body weights were recorded on the day of treatment prior to application and on days 7 and 14. All animals that died spontaneously during the course of the study were necropsied and examined as soon as they were found dead.

Results and discussion

Preliminary study:
none
Effect levels
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 30.1 mL/kg bw
Mortality:
No deaths occurred in the control group and test group treated with 17.8 mL/kg, 23.7 mL/kg and 27.4 mL/kg.
16 out of 20 rats died in the highest treated group (31.6 mL/kg) during the course of the study. All animals died between day 3 and 8.
Clinical signs:
Systemic toxicity was observed in all test item treated groups. All clinical signs disapeared in the lowest treated group (17.8 mL/kg) after day 4 where where as the animals treated with 23.7 mL/kg, 27.4 mL/kg and the surviving animals treated with 31.6 mL/kg still showed clinical signs at the end of the observation period.
Decrease spontaneous activity and reactivity to stimuli, hunched posture with ruffled fur and atxia as well as half-closed eyes was noted within 24 hours after treatment in all 17.8 mL/kg treated animals. Hypothermia was also noted in the same group at the 24-hour observation. Hunched posture with ruffled fur and high-legged walk persisted up to day 4.
Decrease spontaneous activity and reactivity to stimuli as well as ruffled fur appeared in some animals treated at 23.7 mL/kg within 6 hours after treatment. Hunched posture with high-legged walk, half-closed to closed eyes, ruffled fur, tachypnea, alopecia as well as ataxia were noted at the 24-hour reading, persisting until day 2 for ataxia or day 9 for hunched posture with high-legged walk, half-closed to closed eyes and tachypnea. Alopecia, increaed reactivity to stimuli, ruffled fur were still ovserved at the end of the observation period in all animals.
Reduced spontaneous activity, hunched posture with high-legged walk, ruffled fur, tachypnea as well as soft feces were observed within 24 hours after treatement and persisted except for soft feces until the end of the observation period, additionally alopecia, ataxia, increased reactivity to stimuli appeared after the 24-hour reading and persisted up to day 14.
In the high dose level group (31.6 mL/kg), reduced spontaneous activity, hunched posture with high-legged walk, ruffled fur, tachypnea or bradypnea, increased reactivity to stimuli followed by a decrease, ataxia, half-closed eyes and soft feces were noted. High-legged walk, ruffled fur, alopecia persisted in the surviving animals.
Body weight:
Loss of body weight was noted in the 31.6 mL/kg treated group during the first week of observation but the surviving animals did not recover completly at the end of the observation period compared with the control animals. Body weight increased in the other treated groups was comparable to the control group.
Gross pathology:
For the 31.6 mL/kg treated animals, red discoloration of the stomach with hemmorhage was noted at the unscheduled necropsy in 12 out of 16 animals. Blood in the stomach was observed in 5 animals. Red discoloration of the small intestine with hemmorhage was observed in 10 animals and blood in the small intestine was seen in 12 animals.

Applicant's summary and conclusion

Interpretation of results:
relatively harmless
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Oral LD50 male rats > 27.4 and < 31.6 ml/kg
Oral LD50 male rats = 30.1 ml/kg (26.8 g/kg)
density = 0.89g/cm3
Executive summary:

Four groups each of 10 male rats and one group of 20 male rats were treated with the undiluted substance. The single-application volume was 17.8 mL/kg, 23.7 mL/kg, 27.4 mL/kg and 31.6 mL/kg, respectively. One control group with 10 male rats was treated with demineralized water at 31.6 mL/kg.

Mortality and clinical signs were observed during 14 days after treatment.

No deaths occurred in the control group and test groups treated with 17.8 mL/kg, 23.7 mL/kg and 27.4 mL/kg.

16 out of 20 rats died in the highest treated group (31.6 mL/kg) during the course of the study.

Systemic toxicity was observed in all test item treated groups. All clinical signs disapeared in the lowest treated group (17.8 mL/kg) after day 4 where where as the animals treated with 23.7 mL/kg, 27.4 mL/kg and the surviving animals treated with 31.6 mL/kg still showed clinical signs at the end of the observation period.

Loss of body weight was noted in the 31.6 mL/kg treated group during the first week of observation but the surviving animals did not recover completly at the end of the observation period compared with the control animals. Body weight increased in the other treated groups was comparable to the control group.

For the 31.6 mL/kg treated animals, red discoloration of the stomach with hemmorhage was noted at the unscheduled necropsy in 12 out of 16 animals. Blood in the stomach was observed in 5 animals. Red discoloration of the small intestine with hemmorhage was observed in 10 animals and blood in the small intestine was seen in 12 animals.