pymetrozine (ISO); (E)-4,5-dihydro-6-methyl-4-(3-pyridylmethyleneamino)-1,2,4-triazin-3(2H)-one

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 Jul 1991 to 4 Sep 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 OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

1985

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

6-methyl-4-[(E)-[(pyridin-3-yl)methylidene]amino]-2,3,4,5-tetrahydro-1,2,4-triazin-3-one

EC Number:

602-927-1

Cas Number:

123312-89-0

Molecular formula:

C10H11N5O

IUPAC Name:

6-methyl-4-[(E)-[(pyridin-3-yl)methylidene]amino]-2,3,4,5-tetrahydro-1,2,4-triazin-3-one

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Hsd:Sprague Dawley SD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 216 to 294 g (for males), 204 to 268 g (for females)
- Fasting period before study: Yes, approximately 17 to 20 hours before test material administration when food, but not water, was withheld.
- Housing: individually housed in screen-bottom, stainless steel cages (heavy gauge).
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
Animal husbandry and housing comply with standards outlined in the "Guide for the Care and Use of Laboratory Animals" (NIH publication number No. 86-23, revised 1985). Variations from the prescribed environmental conditions existed and were considered to have had no effect on the study outcome. No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study.

IN-LIFE DATES:
July 18 to September 4, 1991

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Destilled

Details on oral exposure:

VEHICLE
- Amount of vehicle: 20.00 mL/kg body weight

Doses:

4000, 5000, 6000, 6500, or 7000 mg/kg of body weight based on range-finding study using the following doses: 1000, 2000, 4000 and 5000 mg/kg of body weight performed with one animal/sex/dose.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were determined before test material administration (Day 0). Additional body weights were determined at Day 7 and at termination of the experimental phase (Day 14) or at death when survival exceeded 1 day.
- Necropsy of survivors performed: yes, All study animals, whether dying during the study or euthanatized, were subjected to a gross necropsy examination and all abnormalities were recorded. After necropsy, the animals were discarded and all tissues with lesions were collected for possible future histological evaluation.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Clinical signs and mortality checks were conducted at approximately 1, 2.5, and 4 hours after test material administration. Additional clinical signs and twice a day mortality checks (morning and afternoon) were conducted daily thereafter for 14 days.

Statistics:

The LD50 value for males, females, and the sexes combined was determined by a computer program utilizing probit analysis. No other statistical analyses were required by the protocol.

Results and discussion

Preliminary study:

No mortality was observed at levels of 1000, 2000, 4000, or 5000 mg/kg. All animals exhibited weight gain with the exception of one male rat which exhibited a weight loss of 8 g during the first week of the study.

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

5 693 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

5 955 mg/kg bw

Based on:

test mat.

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

5 820 mg/kg bw

Based on:

test mat.

Mortality:

At 4000 mg/kg bw there was no mortality. Most deaths at the higher dose levels occurred from day 7 to 13. A data overview can be found in 'Any other information on results incl. tables'.

Clinical signs:

other: The observed signs included hypoactivity, staggered gait, prostration, red-stained face, lacrimation, dyspnea, soft stool, stained urogenital area, redstained urine, tremors, and hypothermia.

Gross pathology:

At necropsy, the most prominent findings were in the DOTs and pertained to the contents and coloration changes in the gastrointestinal tract. The stomach and small intestines contain material of varied consistency and colour that probably represent test material mixed with ingestions. Some of the observations were also attributed to post-mortem change and autolysis or were considered common incidental findings. There were no visible lesions in the animals surviving to the end of the test periods.

Any other information on results incl. tables

 Table 1. Mortality incidence

Dose (mg/kg bw)	Mortality	Onset of death
Males
4000	0/5
5000	1/5	Day 4
6000	3/5	Days 11, 11, 13
6500	4/5	Days 7, 8, 8, 9
7000	5/5	Days 2, 4, 9, 11
Females
4000	0/5
5000	1/5	Day 8
6000	2/5	Days 1, 10
6500	3/5	Days 7, 9, 10
7000	5/5	Days 2, 5, 8, 9, 10

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In this study according to EPA 81-1 guideline the following LD50 values were found: 5693 mg/kg for males and 5955 mg/kg for females.

Executive summary:

In this GLP compliant acute oral toxicity study performed according to EPA guideline 81-1, the test material was evaluated for its acute oral toxicity potential in male and female albino rats (Hsd:Sprague Dawley SD) when administered as a single gavage dose at levels of 4000, 5000, 6000, 6500, and 7000 mg/kg of body weight (5 animals/sex/dose). The test material was dissolved in water. After single exposure, rats were observed for 14 days. Mortality increased with increasing dosis: 0/10, 2/10, 5/10, 7/10 and 10/10 animals receiving 4000, 5000, 6000, 6500 and 7000 respectively. Clinical signs of toxicity included hypoactivity, staggered gait, prostration, red-stained face, lacrimation, dyspnea, soft stool, yellow/red/ or darkstained urogenital area, red-stained urine, tremors, hypothermic to touch, and death. There was no meaningful effect on body weight gain in those animals surviving to termination with the exception of two males which exhibited weight losses of 30 g each during the first week of the study. The most prominent findings observed at necropsy were in the animals dying during the study and pertained to the contents and coloration changes in the gastrointestinal tract. The calculated (probit analysis) oral LD50 was determined to be 5693, 5955, and 5820 mg/kg for males, females, and the sexes combined, respectively.