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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: Crj:CD(SD)IGS
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6 weeks
- Weight at study initiation: males average: 219 g (range: 208 - 238 g), females average: 154 g (range: 138 - 173 g)
- Fasting period before study: 16 hours before administration
- Housing: in the metal bracket type cage
- Diet (e.g. ad libitum): CRF-1 (Oriental Yeast Co., Ltd., Itabashi-ku, Japan) ad libitum
- Water (e.g. ad libitum): tap-water, ad libitum
- Acclimation period: 10 days

ENVIRONMENTAL CONDITIONS
-according to guideline

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:
250, 500, 1000 and 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: day 0, 1, 2, 3, 7, 10 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology and histopathology
Statistics:
VanWaerden test for LD50;
Bartlett and Dunett test for analysis of body weight

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
707 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
812 mg/kg bw
Based on:
test mat.
95% CL:
619 - 1 066
Mortality:
250 mg/kg bw and 500 mg/kg bw: No mortality was observed.
1000 mg/kg bw (males): 5/5 males died; one death occured at day 3, three deaths at day 4 and one death at day 5 after administration.
1000 mg/kg bw (females): 4/5 females died; two deaths occured at day 3, one death at day 4 and one death at day 5 after administration.
2000 mg/kg bw (males): 5/5 males died; four deaths occured at day 3 and one death at day 5 after administration.
2000 mg/kg bw (females): 5/5 females died; one death occured at day 1, two deaths at day 2 and two deaths at day 3 after administration.
Clinical signs:
250 mg/kg bw and 500 mg/kg bw: No abnormalities were observed in both sexes.
1000 mg/kg bw: In the animals that died, reduced locomotor activity, staggering gait, tremors, clonic convulsions, mydriasis, smudging in the peri-genitourinary area or hypothermia were observed in males from the day following administration and in females from day 2 after administration.
2000 mg/kg bw: In the animals that died, reduced locomotor activity, staggering gait, mydriasis or tremors were observed in both sexes from the day following administration.
Body weight:
250 and 500 mg/kg bw: Suppression of weight gain was observed in males until day 2 after administration and in females on the day following administration. However, greater weight gain was observed at the end of the study compared to control animals.
1000 mg/kg bw (males): The body weight decreased until death; significant differences (p<0.01) from control group were found during day 1 - 3 after administration.
1000 mg/kg bw (females): A decrease in body weight was observed until day 3; significant differences (p<0.05) from control animals was indicated at day 2 and day 3 after administration. However, greater weight gain was observed thereafter.
2000 mg/kg bw: In both sexes decrease in body weight was observed until death.
Gross pathology:
1000 mg/kg bw and 2000 mg/kg bw: Necropsy of animals that died revealed malnutrition, a smaller thymus and spleen, smaller mesenteric lymph nodes, dark red foci in the glandular stomach and white foci in the forestomach. In the surviving female of the 1000 mg/kg bw dose group white foci in the forestomach
were seen.
500 mg/kg bw: Necropsy revealed white foci in the forestomach in one female rat.
Other findings:
Histopathology:
Mild to moderate erosion/ulceration and thickening of mucosal epithelium in the forestomach was observed in one male and one female administered 1000 mg/kg bw and in two males administered 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
A single dose oral toxicity test of triallyl isocyanurate in rats revealed LD50 values of 707 mg/kg bw for males and 812 mg/kg bw for females.