1,3,5-Triazine-2,4-diamine, N2,N2,N4,N4-tetrabutyl-6-chloro-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jun 1990 - Feb 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Version / remarks:

1985

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

1982

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Terbuthylazine

EC Number:

227-637-9

EC Name:

Terbuthylazine

Cas Number:

5915-41-3

Molecular formula:

C9H16ClN5

IUPAC Name:

N-tert-butyl-6-chloro-N'-ethyl-1,3,5-triazine-2,4-diamine

Test material form:

solid: particulate/powder

Details on test material:

- Appearance: white powder
- Storage condition of test material: room temperature in the dark

Test animals

Species:

rat

Strain:

other: OFA.SD. (IOPS Caw.)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa-Crédo, France
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 121-161 g
- Housing: group (5)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25
- Humidity (%): 34-90
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10%, 15.9%, 25.1% (w/v)

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

DOSAGE PREPARATION: prepared about 2.5 h before administration

Doses:

1000, 1590, 2510 mg/kg

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: yes
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Bliss' method, Litchfield and Wilcoxon's method to calculate LD50

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

< 1 590 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

1 503 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 030 - <= 2 194

Mortality:

1000 mg/kg: Mortality observed from Day 3 onwards both in males and females
1590 mg/kg: mortality observed from Day 2 (males only) onwards. From Day 3 both sexes affected
2510 mg/kg: mortality observed from Day 2 (males only) onwards. From Day 3 both sexes affected

Clinical signs:

other: 1000 mg/kg: subdued behavior in all animals 4 h after administration, piloerection in half on Day 2, diarrhoea on Day 3 (one animal). All surviving rats recovered on Day 4. 1590 mg/kg: subdued behavior in all animals 4 h after administration, prostration

Gross pathology:

Abnormalities which were observed in animals dead during the study were mainly characterised by a marked congestion of the lungs. One male of group 3 presented with abdominal dropsy (cloudy liquid). No abnormality was noted in animals killed at the end of the study.

Any other information on results incl. tables

Table 1: Mortality observed in the study

Dose level (mg/kg)	Mortality (%) after 15 days
	Males	Females	Males + Females
0	0	0	0
1000	40	20	30
1590	60	60	60
2510	40	80	60

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions chosen, mortality was observed from 1000 mg/kg onwards. The LD50 for females (most sensitve) was calculated to be 1503 mg/kg.

Executive summary:

The test article was administered once only, in suspension in purified water and at the dose levels of 1000, 1590 and 2510 mg/kg, by the oral route (gastric gavage), in the Sprague-Dawley rat (5 males + 5 females per group). This study was performed in comparison with a control group of 10 rats (5 males + 5 females) treated with the vehicle under the same conditions. Mortality and abnormal clinical signs were noted 15 minutes after intubation, then at 1, 2 and 4 hours, and then daily for the l4 day study period. All the animals were weighed the day before treatment (Day-l), immediately before administration of the test article (Day 1), on Days 8 and 15, as well as at time of death from Day 2 onwards. A necropsy was performed for all the animals dead during the study and for all surviving rats after the l4 day study period and the final observation (Day 15). Mortality was observed from the lowest concentration onwards. The LD50 for males, females and males and females combined was calculated with the Bliss' method to be < 1590 mg/kg, 1503 mg/kg, and 1590 mg/kg, respectively.