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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:
May-June, 1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, GLP-like quality assurance

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report date:
1985

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Remarks:
but conducted under GLP-like quality assurance with QAU statement included
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
1-(N,N-bis(2-ethylhexyl)aminomethyl)-1,2,4-triazole
EC Number:
401-280-0
EC Name:
1-(N,N-bis(2-ethylhexyl)aminomethyl)-1,2,4-triazole
Cas Number:
91273-04-0
Molecular formula:
C19 H38 N4
IUPAC Name:
1-(N,N-bis(2-ethylhexyl)aminomethyl)-1,2,4-triazole
Details on test material:
- Physical state: liquid
- Analytical purity: commercial grade
- Storage condition of test material: room temperature

Test animals

Species:
rat
Strain:
other: TIF:RAIf (SPF), F3-crosses of RII 1/Tif x RII 2/Tif
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY LTD. Tierfarm, 4334 Sisseln, Switzerland
- Age at study initiation: 7-8 weeks
- Weight at study initiation: 165 - 220 g
- Fasting period before study: overnight fasting
- Housing: caged in groups of 5 in Macrolon cages type 4 with standardized soft wood bedding
- Diet: Rat food, NAFAG No. 890, NAFAG AG, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3° C
- Humidity (%): 55+15%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80
Details on oral exposure:
DOSE VOLUME APPLIED
10 mL/kg bw
Doses:
1000, 2000, and 5000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations:
Mortality: daily; a.m. and p.m. on working days, a.m. on weekend days
Signs and symptoms: 1, 2, 3 and 5 hours post dose and then daily
Body weight: on days 1, 7, 14 and at death
- Necropsy of survivors performed: yes; spontaneously dying animals were submitted to a gross necropsy as soon as possible; survivors at the end of the observation period.
Statistics:
From the body weights, the group means and their standard deviations were calculated.
The LD50 values (including their 95% confidence limits) were computed by the logit model.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
2 505 mg/kg bw
Based on:
test mat.
95% CL:
1 616 - 5 058
Sex:
female
Dose descriptor:
LD50
Effect level:
2 238 mg/kg bw
Based on:
test mat.
95% CL:
1 375 - 4 014
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 356 mg/kg bw
Based on:
test mat.
95% CL:
1 810 - 3 307
Mortality:
No mortality occurred in the 1000 mg/kg bw group. 3 animals died in the 2000 mg/kg bw group (1 male and 2 females), and all (10) animal died in the 5000 mg/kg bw group.
Clinical signs:
Dyspnea, exophthalmos, ruffled fur, and abnormal body positions were seen, being common symptoms in acute tests.
Additionally, diarrhea was observed in the two lower dose groups on the administration day, in the highest dose group up to four days after the administration.
In the 2000 and 5000 mg/kg dose groups, sedation was detected up to day 4 after the administration and chromodacryorrhea between days 2 and 4 after the administration.
Tremor was seen in the 2000 mg/kg bw dose group on the administration day and on day 1.
The surviving animals recovered within 10 - 12 days.
Body weight:
Not impaired.
Gross pathology:
No deviations from normal morphology were found in the 1000 mg/kg bw dose group.
Gastrointestinal dilatations were observed in two females of the 2000 mg/kg bw dose group and in six animals of the 5000 mg/kg bw dose group. Hemorrhagic lungs were detected in one male each of the 2000 and 5000 mg/kg bw dose groups. In one female of the 5000 mg/kg bw dose group, fluid contents of the thoracic cavity was found.
In the 2000 mg/kg bw dose group, in one female hemorrhagic contents was found in the abdominal cavity.

Applicant's summary and conclusion

Conclusions:
Upon an acute oral administration and a 14 day post-treatment observation period, the LD50 (with 95% confidence limits calculated, where possible) was determined to be 2356 (1810-3307) mg/kg bw.
Executive summary:
In an acute oral toxicity test according to OECD guideline 401 and performed under GLP-like quality control, groups of 5 male and 5 female rats were treated with the test substance by oral gavage administration at dosage levels of 1000, 2000 and 5000 mg/kg body weight. The test item was diluted in distilled water containing 0.5% carboxymethylcellulose and 0.1% polysorbate 80. All animals were observed 1, 2, 3 and 5 hours postdose and then once daily for 14 days for signs and symptoms. The animals were observed twice daily for mortality and body weights were recorded on days 1, 7, 14 and at death. All animals were necropsied and examined macroscopically. No mortality occurred in the 1000 mg/kg body weight group. In the 2000 mg/kg bw group, 1 male and 2 females died and all animal died in the 5000 mg/kg bw group. Dyspnea, exophthalmos, ruffled fur, and abnormal body positions were seen, being common symptoms in acute tests. Additionally, diarrhea was observed in the two lower dose groups on the administration day and in the highest dose group up to four days after the administration. Tremor was seen in the 2000 mg/kg bw dose group on the administration day and on day 1. In the 2000 and 5000 mg/kg dose groups, sedation was detected up to day 4 after the administration and chromodacryorrhea between days 2 and 4 after the administration. The surviving animals recovered within 10 - 12 days. During necropsy, no deviations from normal morphology were found in the 1000 mg/kg bw dose group. Gastrointestinal dilatations were observed in two females of the 2000 mg/kg bw dose group and in six animals of the 5000 mg/kg bw dose group. In addition, hemorrhagic content was found in the abdominal cavity in one female of the 2000 mg/kg bw dose group. Hemorrhagic lungs were detected in one male each of the 2000 and 5000 mg/kg bw dose groups. In one female of the 5000 mg/kg bw dose group, fluid contents of the thoracic cavity was found. The resulting LD50 values with 95% confidence limits were calculated to be 2505 (1616-5058) mg/kg bw in males, 2238 (1375-4014) mg/kg bw.in females and 2356 (1810-3307) mg/kg bw.in both sexes.