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

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1994/02 to 1994/08

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Version / remarks:

FIFRA § 10, Subdivision F, 1984

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

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:

Fine white powder

Specific details on test material used for the study:

Storage: Room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

HSD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
Acclimation Period: At least 4 days
Weight When Tested: Males (179-225 g); Females(195-242 g)
Age: Young adult
Housing: One per cage

ENVIRONMENTAL CONDITIONS:
Temperature Range: 67-77 °F (19.4-25 °C)
Humidity Range: 30-80%
12-hour light/dark cycle
10-12 air changes/hour

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 3.92 - <= 6.68 µm

Geometric standard deviation (GSD):

>= 2.075 - <= 4.142

Remark on MMAD/GSD:

The MMAD’s were 6.68 µm ±1.48 for the 3.60 mg/L (3600 mg/m3) concentration and 3.92 µm ±1.48 for the 0.744 mg/L (744 mg/m3) concentration.
GSD ranges: (2.947 to 4.142) at 3.60 mg/L concentration and (2.075 to 4.027) at 0.744 mg/L concentration.

Details on inhalation exposure:

A 500 L nose-only stainless steel, dynamic flow inhalation chamber was utilized in this experiment. The body of the chamber has 25 ports in 5 rows. Polycarbonate cones are inserted into 10 designated individual ports. The test material is introduced through the opening in the top of the chamber. The bottom section has a corresponding air outlet and a drain valve for cleaning the chamber. The individual polycarbonate cones (tubes) are tapered at one end to t the shape of the animal’s head and the back portion is sealed with a polycarbonate cap. The cones containing the animals fit tightly into the ports, and are sealed with "0" rings.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

The mean concentration was 0.744 or 3.6 mg/L (744 or 3600 mg/m3).

No. of animals per sex per dose:

5

Control animals:

yes

Remarks:

A control group of 5 rats/sex was exposed to air only under similar experimental conditions.

Details on study design:

On Day 0 of the study, 5 Sprague Dawley rats/sex/group were exposed nose-only for a single 4-hour period to an aerosol generated from undiluted cyromazine technical at a mean concentration of 0.744 or 3.6 mg/L (744 or 3600 mg/m3). A control group of 5 rats/sex was exposed to air only under similar experimental conditions. During the 4- hour period 4 samples of the tested atmosphere were taken at regular intervals for the determination of exposure levels. Particle size distribution was also determined during exposure. Clinical signs were recorded twice on the day of exposure and at least daily thereafter for up to 17 days. Body weights were measured prior to exposure, on day 7 and at the day of termination. At termination of the study, all animals were subjected to gross necropsy.

Results and discussion

Preliminary study:

Trial assays were conducted using different methods of aerosolizing the test material into the exposure chamber in attempts to determine which method(s) would produce the highest concentration and a mass median aerodynamic diameter (MMAD) between 1 and 4 µm.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 3.6 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred.

Clinical signs:

other: Decreased activity, piloerection at both concentrations, and additionally nasal discharge at the higher concentration tested. All animals appeared normal two days post treatment and for the rest of the study period.

Body weight:

Body weight gain was unaffected with the exception of two females exposed to 3.6 mg/L and two control females, which lost weight between days 0 and 7.

Gross pathology:

Gross necropsy revealed discoloration of the lungs in animals of all groups.

Any other information on results incl. tables

Table 1:

Exposure parameters

Parameter	Value
	Low Concentration	High Concentration
Nominal concentration	4.51 mg/L	45.4 mg/L
Analytical concentration	0.7443 mg/L	3.597 mg/L
Standard deviation (SD)	1.48	1.48
MMAD ± SD (µm)	3.92	6.68
% of particles collected	50% with MMAD < 5.90µm	50% with MMAD < 3.54µm
	84% with MMAD < 23.79µm	84% with MMAD < 7.35µm

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation LC50 value for cyromazine in male and female Sprague Dawley rats under the examined conditions was found to be greater than 3.6 mg/L air (maximum attainable concentration).

Executive summary:

Two groups of Sprague-Dawley rats (5/sex/group) were exposed for four hours to an aerosol generated from undiluted Cyromazine in a nose-only inhalation at a mean concentration of 0.744 or 3.60 mg/L (744 or 3600 mg/m³). A control group consisting of 5 males and 5 females was exposed to room air only for four hours under similar experimental conditions. There was no mortality during the study. Clinical signs of toxicity in the test groups included activity decrease and piloerection at both levels, and nasal discharge at the 3.60 mg/L level. All animals were asymptomatic on Day 2. Body weights were essentially unaffected by exposure, except for two females at the 3.60 mg/L level that lost weight between Days 0 and 7. Control animals appeared normal throughout the study. The gross necropsies of control as well as test animals showed some discoloration of lungs. The acute inhalation LD₅₀ for Cyromazine is greater than the maximum attainable concentration of 3.60 mg/L.