Propanoic acid, 2-(4-chloro-2-methylphenoxy)-, 2-ethylhexyl ester, (2R)-

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 19, 1992 - September 9, 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1150 (Acute inhalation toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EPA FIFRA 81-3

Test guideline 3

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

fixed concentration procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-Ethylhexyl (R)-2-(2-methyl-4chlorophenoxy)propionate

EC Number:

630-324-3

Cas Number:

861229-15-4

Molecular formula:

C18H27ClO3

IUPAC Name:

2-Ethylhexyl (R)-2-(2-methyl-4chlorophenoxy)propionate

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- batch No.of test material: 5007
- sample No.:1505E
- Expiration date of the lot/batch: March 1993

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 4°C in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK
- Age at study initiation: 6 weeks (male) and 8 weeks (female)
- Weight at study initiation: ca. 200 g
- Housing: stainless steel cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°C - 24°C
- Humidity (%): 25% - 65%
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

2.2 µm

Geometric standard deviation (GSD):

2.31

Remark on MMAD/GSD:

The proportion of droplets in the sub-micron size range was 17.8% and lower that EPA specification of 25%. Calculations show, that the 25% level was reached at a particle size of 1.23 µm.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: aerosol generator; test substance was supplied from syringe driven at a constant rate by a syringe pump
- Exposure chamber volume: chamber with an internal volume of 120 L
- Method of holding animals in test chamber: chamber divided by wire mesh partitions to provide 10 separate animal compartments
- Source and rate of air: flow rate of 0.6 mL/min to give a concentration of 5 mg/L of air
- Temperature in air chamber:mean 23°C measured at the start and then at 30-minute intervals during exposure

TEST ATMOSPHERE
- analytical method used: HPLC
- Samples taken from breathing zone: yes, 5 samples during exposure

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0 and 4.66 mg/L (highest achieved concentration)

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: continuously during exposure and at least twice daily throughout the observation period; daily weighting from start until the end of the experiment
- Other examinations performed: food and water consumption was measured daily; macroscopic examination of all animals, lungs, liver and kidneys examined

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 4.66 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

One exposed female died overnight following exposure.

Clinical signs:

other: CLINICAL SIGNS. During exposure : signs consistent with exposure to an irritant aerosol, including partial closing of the eyes, wetness around the mouth and snout, and exaggerated respiratory movements. During observation period: signs seen in rats includ

Body weight:

Reduced bodyweight or reduced rate of bodyweight gain was evident for up to 5 days following exposure. Subsequently, weight gain was similar to that for control rats.

Gross pathology:

The lung weight to bodyweight ratio for the rat that died was higher than for the surviving rats.
Macroscopic pathology: the lungs of the rat that died following exposure the substance were congested and the stomach was gas-filled.

Other findings:

- Organ weights:
The lung weights were within normal limits for the control rats and for the surviving rats exposed to the test substance.. For the rat taht died the lung weight to bodyweight ratio was higher than for the surviving rats.

- Histopathology: The lungs of one rat exposed to the test substance were congested and the stomach was gas-filled. There were no abnormalities in any other rat.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50 (4-hour) for MCPP-P 2-EHE is in excess of 4.66 mg/L. This was the highest attainable concentration.

Executive summary:

In a GLP study according to OECD 403, the acute inhalation toxicity of MCPP-P 2-EHE was assessed by exposing a group of rats to an aerosol produced from the test item. The control group was exposed to air only. The exposure duration was 4 hour in a whole body chamber followed by a 14-days observation period. The concentration of aerosol was measured during the exposure and the particle size distribution was assessed as well.

One female died following exposure and all animals showed signs of constant exposure to an irritant aerosol, including partial closing of the eyes, wetness around the mouth and snout and exaggerated respiratory movements. During the observation period, rats showed abnormal breathing, lethargy, wet fur, matted or oily fur and brown staining around the snout and jaws, but all surviving rats exposed to the test item were normal by day 8 of observation. The body weight was reduced for up to 5 days following exposure to MCPP-P 2-EHE but subsequently, weight gain was similar to that for control rats. Food consumption was reduced for up to one day following exposure and water consumption increased and remained high for several days following exposure to the test item. The lung weight to bodyweight ratios for rats surviving expose were within normal limits.