Simazine

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 February - 17 March 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Simazine

EC Number:

204-535-2

EC Name:

Simazine

Cas Number:

122-34-9

Molecular formula:

C7H12ClN5

IUPAC Name:

6-chloro-N2,N4-diethyl-1,3,5-triazine-2,4-diamine

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

TEST MATERIAL
- Test material: Simazine Technical
- Description: White crystalline powder
- Purity: 97.89% a.i. (provided by Sponsor)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability: Not provided to testing facility

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Texas Animal Specialties, Humble, TX
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 2 months
- Weight at study initiation: Males: 268 - 327 g; Females: 194 - 229 g
- Housing: suspended, wire bottom, stainless steel cages; one animal per cage
- Diet: PMI™ Lab Diet Formula #5008, available ad libitum except during the exposure period
- Water: municipal water supply available ad libitum except during the exposure period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C (actual 20 - 22°C)
- Humidity (%): 30 - 70% (actual 29 - 86%)
- Air changes (per hr): 10-12
- Photoperiod (hrs dark / hrs light): 12 hour light/ dark cycle

IN-LIFE DATES: From: 3 March 2009 To: 17 March 2009

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Mass median aerodynamic diameter (MMAD):

2.8 µm

Geometric standard deviation (GSD):

5.9

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: nose-only stainless steel, dynamic flow inhalation chamber
- Exposure chamber volume: 500 L
- Method of holding animals in test chamber: Polycarbonate tubes
- Source and rate of air: 34.7 air changes per hour
- System of generating particulates/aerosols: The aerosol was generated by a Venturi Aspirator which aspirated the test substance from a coupled motorised revolving disc delivery system, then sprayed the resulting aerosol directly into the exposure chamber.
- Method of particle size determination: Determined twice during the exposure using a cascade impactor at a rate of 7.8 L/minute for 25 seconds.

TEST ATMOSPHERE
- Brief description of analytical method used: The concentration of test substance in the exposure atmosphere was determined gravimetrically twice per hour and nominally at the end of the exposure. The gravimetric concentration was determined by passing a known volume of exposure air through a pre-weighed filter and dividing the amount of test substance deposited on the filter by the volume of air which passed through the filter. The nominal concentration was determined by dividing the loss in weight of the test substance after the exposure by the total volume of air that passed through the chamber.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- Particle size distribution:
- 1.25 h distribution: ≤ 0.2 µm - 5% of particles collected
≤ 0.5 µm - 16%
≤ 2.8 µm - 50%
≤ 16.8 µm - 84%
≤ 52.6 µm - 95%
- 2.25 h distribution: ≤ 0.2 µm - 5% of particles collected
≤ 0.6 µm - 16%
≤ 2.9 µm - 50%
≤ 13.9 µm - 84%
≤ 38.6 µm - 95%
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.25 h distribution: MMAD 2.8 µm (GSD 5.9); 2.25 h distribution: MMAD 2.9 µm (GSD 4.9)

Duration of exposure:

4 h

Concentrations:

2.21 mg/L

No. of animals per sex per dose:

5 animals per sex

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for mortality and signs of pharmacological and/or toxicological effects were made frequently on the day of exposure and at least once daily thereafter. Individual bodyweights were recorded just prior to exposure and on Days 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.21 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

There was no mortality during the study.

Clinical signs:

other: Prominent in-life observations included activity decrease and piloerection. Animals were asymptomatic by Day 4.

Body weight:

Body weight gain was unaffected by the administration of the test substance, except in one female that lost 2 g between Days 7 and 14.

Gross pathology:

No abnormalities were observed.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation LC50 for Simazine Technical was >2.21 mg/L in male and female rats.