Registration Dossier

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:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
traditional method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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:
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.