N-cyclopropyl-1,3,5-triazine-2,4,6-triamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004/08/23 to 2004/11/29

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

December 2001

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

N-cyclopropyl-1,3,5-triazine-2,4,6-triamine

EC Number:

266-257-8

EC Name:

N-cyclopropyl-1,3,5-triazine-2,4,6-triamine

Cas Number:

66215-27-8

Molecular formula:

C6H10N6

IUPAC Name:

N2-cyclopropyl-1,3,5-triazine-2,4,6-triamine

Test material form:

solid: particulate/powder

Remarks:

white to light beige crystalline

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

albino

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult (9-11 weeks)
- Weight at study initiation: 176-212 grams
- Fasting period before study: Overnight
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Water: Filtered tap water was supplied ad-libitum by an automatic water dispensing system.
- Acclimation period: 9-20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25ºC
- Photoperiod: 12-hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

Distilled water

Details on oral exposure:

The test substance was administered as a 40% w/w suspension in a 1% w/w solution of CMC in distilled water using a stainless steel ball-tipped gavage needle attached to an appropriate syringe. Following administration, each animal was returned to its designated cage. Feed was replaced approximately 3-4 hours after test substance administration.

Doses:

Single dose, 2,000 mg/kg bw

No. of animals per sex per dose:

5 females/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights of the animals were recorded prior to test substance administration (initial-Day 0) and again on Days 7 and 14 (termination) following dosing or after death.
- Necropsy of survivors performed: yes. Surviving rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on the decedent and all euthanized animals.
- Examinations performed: mortality, signs of gross toxicity, behavioral changes, clinical signs, body weight, tissues and organs observation

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal died within 24 hours following test substance administration.

Clinical signs:

other: Apart from hypoactivity and ano-genital staining noted for one surviving animal on Day 1, all survivors appeared active and healthy during the study.

Gross pathology:

Gross necropsy of the decedent revealed discoloration of the intestines. No gross abnormalities were noted for the euthanized animals necropsied at the conclusion of the 14-day observation period.

Any other information on results incl. tables

Results are provided in the overall remarks section below.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study, the acute oral LD50 of cyromazine was greater than 2,000 milligrams per kilogram of body weight in female rats.

Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with rats to determine the potential for Cyromazine to produce toxicity from a single dose via the oral route. Under the conditions of this study, the acute oral LD50 of the test substance was greater than 2,000 milligrams per kilogram of body weight in female rats.
An initial limit dose of two thousand milligrams of the test substance per kilogram of body weight was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, four additional females were dosed in sequence at the same dose level. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing or until death occurred. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) following dosing or after death. Necropsies were performed on all animals.
One animal died following test substance administration. Toxic signs noted prior to death included hypoactivity and ano-genital staining. Apart from ano-genital staining and soft feces noted for one surviving animal on Day 1, all survivors appeared active and healthy during the study and gained body weight over the 14-day observation period. Gross necropsy of the decedent revealed discoloration of the intestines. No gross abnormalities were noted for the euthanized animals necropsied at the conclusion of the 14-day observation period.