α-n-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25-January-2006 to 25-May-2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: JMAFF, Acute Inhalation Toxicity Study

Version / remarks:

200

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

1998

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

α-n-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile

EC Number:

410-400-0

EC Name:

α-n-butyl-α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile

Cas Number:

88671-89-0

Molecular formula:

C15H17ClN4

IUPAC Name:

2-(4-chlorophenyl)-2-[(1H-1,2,4-triazol-1-yl)methyl]hexanenitrile

Test material form:

solid

Remarks:

light tan-colored solid.

Test animals

Species:

rat

Strain:

Fischer 344/DuCrj

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Inc. (Raleigh, North Carolina)
- Age at study initiation: 9 weeks
- Housing: Animals were housed one per cage in stainless steel cages
- Diet: LabDiet® Certified Rodent Diet in pelleted form
- Water: Municipal drinking water, ad libitum
- Acclimation period: Animals were acclimated to the nose cones for at least two hours on the day preceding exposure to the test material
- Method of randomization in assigning animals to test and control groups: Before administration of test material began, animals were stratified by body weight and then randomly assigned to treatment groups using a computer program designed to increase the probability of uniform group mean weights and standard deviations at the start of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C with a tolerance of ± 1°C (and a maximum permissible excursion of ± 3°C)
- Humidity (%): 40-70%
- Air changes (per hr): Approximately 12-15 times/hour
- Photoperiod (hrs dark / hrs light): 12-hour light/dark photocycle

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

3.5 µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

The mass concentration of aerosol present in the chamber was determined gravimetrically three times during the exposure period.

Duration of exposure:

4 h

Concentrations:

The resulting time-weighted average concentration was 5.88 mg/L; the nominal concentration was 17.14 mg/L (calculated based on the mass of test material fed into the generation system divided by the total chamber airflow during the exposure period.).

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: All animals were observed for morbidity and mortality at least twice daily. Animals were weighed and observed for exposure-related effects approximately every 30 minutes during the exposure period. All rats were weighed on test days 2, 4, 8, 11, and 15 during the two-week post-exposure period.
- Necropsy of survivors performed: yes
- Clinical signs including body weight: Detailed clinical observations (DCO) were conducted pre-exposure and daily following the start of treatment.
- Other examinations performed: The necropsy included the examination of the eyes with a microscope slide using fluorescent illumination. Tissues were not saved and no histopathologic examinations were performed.

Statistics:

Means and standard deviations were calculated for descriptive purposes for chamber concentration (mean only), animal body weights, exposure room temperature and chamber temperature, humidity, and airflow.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.88 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: tested at the maximum attainable concentration

Mortality:

All animals survived the four-hour exposure to the test material as well as the two week post-exposure period.

Clinical signs:

other: See below.

Body weight:

Mean body weight losses of 7.7% and 9.3% were noted for male and female rats, respectively, on test day 2. Pre-exposure mean body weight values were exceeded on test day 8.

Gross pathology:

There were no treatment-related visible lesions noted in any of the rats exposed to myclobutanil at the test day 15. However, one female rat was found to have decreased body fat at the gross necropsy.

Other findings:

Clinical effects noted during the four-hour exposure period were limited to soiling of the haircoat in three male rats and one female rat. In-life observations noted post-exposure included combinations of noisy and/or labored respiration with and without mouth-breathing, decreased resistance to removal, decreased reactivity, decreased feces and urine, perineal, perioral, perinasal, periocular, abdominal and/or extensive body soiling, dehydration and ungroomed appearance. Some of the rats eyes were partially closed due to the physical characteristics of the test material. In addition, one female rat had decreased extensor-thrust response and muscle tone, bilateral palpebral closure, and poor coordination. This female rat was normal by test day 9.
All other rats appeared normal by test day 7.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on these data, the four-hour LC50 of inhaled particulate myclobutanil is greater than 5.88 mg/L (the maximum attainable concentration) for male and female Fischer 344 rats.

Executive summary:

An acute inhalation study was performed with Myclobutanil. Groups of five rats/sex were exposed for four hours, using a nose-only inhalation exposure system, to a time-weighted average chamber concentration of 5.88 mg myclobutanil per liter of air (the maximum attainable concentration). All animals survived the four hour exposure to the test material as well as the two week post-exposure period. Clinical effects noted during the four-hour exposure period were limited to soiling of the haircoat in three male rats and one female rat. In life observations noted post-exposure included combinations of noisy and/or labored respiration with and without mouth-breathing, decreased resistance to removal, decreased reactivity, decreased feces and urine, perineal, perioral, perinasal, periocular, abdominal and/or extensive body soiling, dehydration, and ungroomed appearance. The eyes of some of the rats were partially closed due to the physical characteristics of the test material. In addition, one female rat had decreased extensor-thrust response and muscle tone, bilateral palpebral closure, and poor coordination. This female rat was normal by test day 9. All other rats appeared normal by test day 7. Mean body weight losses of 7.7 and 9.3% were noted for male and female rats, respectively, on test day 2. Pre-exposure mean body weight values were exceeded on test day 8. Based on this data, the four-hour LC50 of inhaled particulate myclobutanil is concluded to exceed the maximum attainable concentration (5.88 mg/L).