1-(N,N-bis(2-ethylhexyl)aminomethyl)-1,2,4-triazole

Acute Toxicity: oral

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:

guideline study

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:

yes

Remarks:

Conducted under GLP-like quality assurance with QAU statement included

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

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:

bis(2-ethylhexyl)[(1H-1,2,4-triazol-1-yl)methyl]amine

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 levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

2 356 mg/kg bw

Based on:

test mat.

95% CL:

1 810 - 3 307

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

2 505 mg/kg bw

Based on:

test mat.

95% CL:

1 616 - 5 058

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

2 238 mg/kg bw

Based on:

test mat.

95% CL:

1 375 - 4 014

Mortality:

0/10 mortality occurred in the 1000 mg/kg bw group. 3/10 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:

other: 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 t

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 haemorrhagic contents were found in the abdominal cavity.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

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.