Methyl (R)-2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF 2-1-3

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl (R)-2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

EC Number:

406-250-0

EC Name:

Methyl (R)-2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)phenoxy)propionate

Cas Number:

72619-32-0

Molecular formula:

C16H13ClF3NO4

IUPAC Name:

methyl 2-(4-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy}phenoxy)propanoate

Test material form:

solid

Specific details on test material used for the study:

Haloxyfop-R methyl ester Technical
Lot # 1E311501H1 (TSN303644)
Purity: 95.6%

Test animals

Species:

rat

Strain:

other: RCCHan:WIST

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 11 to 12 weeks
- Weight at study initiation: 234-270 g for female Rats; 352-393 g for male Rats
- Housing: Five rats/cage
- Diet: Rat pellet feed, Teklad Certified Global High Fiber Rat/Mice feed manufactured by Harlan, USA was provided, ad libitum
- Water: UV sterilized water filtered through Kent Reverse Osmosis water filtration system was provided ad libitum
- Acclimation period: 7 to 8 days
- Method of randomisation in assigning animals to test and control groups: Rats were randomly allocated to different groups using in-house developed and validated computer software

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 23 °C
- Humidity: 64 to 67%
- Air changes: Minimum 15 air changes/hour
- Photoperiod: 12 h dark/ 12 h light

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: polypropylene glycol P400

Mass median aerodynamic diameter (MMAD):

2.52 µm

Geometric standard deviation (GSD):

2.42

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The dynamic inhalation equipment has 3 main parts namely inlet, exposure and outlet chambers. Each part is 30 cm in height and 30 cm in internal diameter.
- Exposure chamber volume: The total capacity of the chamber is 63.5 litres.
- Method of holding animals in test chamber: Each rat was restrained in a single transparent perspex exposure tube with adjustable unit. The exposure tubes were accommodated in the port-holes of the inhalation chamber. The adjustable unit of the exposure tube was set so that the animals breathed the test substance aerosols through the window panel of the exposure tube.
- Source and rate of air (airflow): The inlet unit (upper) consists of a glass cylinder with facility for the attachment of a spray atomizer. The air inflow and outflow rates were maintained at 15 and 20 liters per minute, respectively, and were monitored throughout the exposure period.
- System of generating particulates/aerosols: Prepared test item was loaded into a 60 mL infusion syringe, positioned on the continuous infusion syringe pump. The test item was infused at the rate of 7 mL/h to generate the aerosols with the help of a spray atomizer.
- Method of particle size determination: Aerosols from the chamber are drawn into the cascade impactor (7 stages) with pre-weighed stainless steel collection plates using a vacuum pump. At the end of the sampling period (10 minutes), the collection plates with test item are disassembled and weighed. The increase in the weight of each collection plate is the mass of particles in the size range of that impact stage. The total mass of particles and the percent mass of particles in each size range is calculated. The mean cumulative percent particle size is calculated for a required particle size by adding the mean particle size distribution from 0 to that required particle size.
- Treatment of exhaust air: The outlet unit (lower) is made of stainless steel with an outlet provision connected to a suction pump. The outgoing air from the chamber passes through an impinger containing 1.0% sodium hydroxide solution and moisture traps.
- Temperature, humidity, pressure in air chamber: The chamber temperature during the exposure period was between 20.4 and 22.4°C, while the relative humidity was between 36.2% and 44.7%. The chamber oxygen concentration recorded during the exposure period ranged between 20.4 and 20.9%.

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: During preliminary chamber work, gravimetric samples were collected and analyzed to determine the chamber aerosol concentration. The concentration of aerosol present in the chamber was determined gravimetrically at three times during the four-hour exposure period. The aerosol particles were collected on pre-weighed glass fiber filters. The suitability and efficiency of the gravimetric sampling train (filter plus sorbent tubes) was determined by applying a known mass of the test item onto the open-face filter, and then drawing dry, particle free air, through the sampling train at the flow rate and for the same length of time that was used during the study.
- Samples taken from breathing zone: yes
- Time needed for equilibrium of exposure concentration before animal exposure : 15 min

VEHICLE
- Concentration of test material in vehicle: 50%
- Lot/batch no.: 3BCBK1831V

TEST ATMOSPHERE
- Mass Median Aerodynamic Diameter (50% MMAD) = 2.52 μm; GSD: 2.42

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

Group I (vehicle control): Aerosolized polypropylene glycol P400 at a nominal concentration of 7.86 mg/L air
Group II: 2.50 mg test substance/L air

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All rats were observed for any signs of toxicity and mortality at hourly intervals during the 4 h exposure period and at 1 and 2 h after the exposure on the day of exposure. Subsequently, the surviving rats were observed twice a day for morbidity and mortality for a period of 14 days following exposure. Body weights were recorded prior to exposure on day 0 and on post-exposure days 1, 3, 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.5 mg/L air

Based on:

other: time-weighted average concentration

Exp. duration:

4 h

Mortality:

None

Clinical signs:

other: nasal irritation

Body weight:

One day after exposure, rats exposed to 2.50 mg/L test substance had slightly reduced body weights compared to their pre-exposure values but gained weight throughout the remainder of the post-exposure observation period and exceeded their pre-exposure body weights by day 7.

Gross pathology:

No abnormality

Applicant's summary and conclusion

Conclusions:

Rat inhalation LC50 (male/female): >2.50 mg/L air

Executive summary:

In an acute inhalation toxicity study conducted according to the guidelines OECD 403, OPPTS 870.1300, EC 440/2008 B.2 and JMAFF 2-1-3, two groups of rats each comprising five males and five females (11 to 12 weeks old) were used for the study. Rats from group I were exposed to aerosolized polypropylene glycol P400 at a nominal concentration of 7.86 mg/L air and served as the vehicle control group for the second experimental group (Group II) that were exposed to a time-weighted average concentration (TWA) of 2.50 mg test substance/L air using a nose-only inhalation exposure system. The rats in both groups were exposed for 4 h followed by a 14 day post-exposure observation period.

The mass median aerodynamic diameter (MMAD) of aerosolized test substance was determined to be 2.52 μm with an average geometric standard deviation (GSD) of 2.42.

Treatment-related clinical sign of nasal irritation was observed immediately post-exposure in rats exposed to 2.50 mg/L air (TWA) but not in control group rats exposed to the vehicle polypropylene glycol P400.

No treatment-related mortality or gross necropsy findings were observed in either the control or test substance-exposed groups. One day after exposure, rats exposed to 2.50 mg/L had slightly reduced body weights compared to their pre-exposure values but gained weight throughout the remainder of the post-exposure observation period and exceeded their pre-exposure body weights by day 7.

Exposure to aerosolized propylene glycol P400 had no effect on the body weight of control rats. All control rats gained weight throughout 14-day post-exposure period. The 4 h acute inhalation median lethal concentration (LC50) of the test substance in male and female Wistar rats was found to be greater than the time-weighted average concentration of 2.50 mg/L air.

Based on the results of this study, an indication of the classification for the test substance is as follows:

EPA Toxicity Categories (December 2002): Unclassified