2,6-dibromo-4-cyanophenyl heptanoate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 Aug - 21 Sep 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 2009

Deviations:

yes

Remarks:

Limited information on environmental conditions, exposure and test atmosphere generation.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

traditional method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,6-dibromo-4-cyanophenyl heptanoate

EC Number:

260-300-4

EC Name:

2,6-dibromo-4-cyanophenyl heptanoate

Cas Number:

56634-95-8

Molecular formula:

C14H15Br2NO2

IUPAC Name:

2,6-dibromo-4-cyanophenyl heptanoate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Sprague Dawley, Inc., Houston, Texas
- Females nulliparous and non-pregnant: yes
- Age at study initiation: young adult
- Weight at study initiation: 299 - 370 g (males), 176 - 240 g (females)
- Housing: in groups of 1-3, separated by sex, in suspended, wire bottom, stainless steel cages
- Diet: Purina Formulab Chow #5008, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported

IN-LIFE DATES: From: 31 Aug To: 21 Sep 1989

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

> 1.651 - < 1.978 µm

Geometric standard deviation (GSD):

> 1.866 - < 2.279

Remark on MMAD/GSD:

Details can be found in Attachment 1.

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 200 L New York University design, stainless steel, dynamic flow inhalation chamber
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber: not specified
- Source and rate of air (airflow): 73.3 - 77.6 L/min
- System of generating particulates/aerosols: aerosol was generated by pumping the test material through a pressure operated spray nozzle. This was then diluted with dried and filtered air and drawn into the exposure chamber.
- Method of particle size determination: Particle size determinations were made using an Andersen cascade impactor.
- Temperature, humidity, pressure in air chamber: Temperature and humidity were recorded at 30 minute intervals during the exposure period from a Taylor wet bulb/dry bulb hygrometer located in the exposure chamber, temperature ranged from 22.8 - 25.5 °C, relative humidity from 59 - 75%, air pressure was not specified.

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: Analysis of the concentration of the test atmosphere was performed according to a modification of the method provided by the sponsor using a Tracer Model 560 gas chromatograph. The nominal concentration was determined by dividing the loss in weight of the test material after each exposure by the total volume of air which passed through the chamber.
- Time needed for equilibrium of exposure concentration before animal exposure: not reported
- Particle size distribution: Please refer to Attachment 1

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Nominal: 1.94 , 8.54 and 21.1 mg/L
Measured: 0.523, 1.45 and 2.69 mg/L

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: on the day of exposure and at least once daily thereafter. Due to chamber design, only 4 animals (2 males and 2 females, for example) could be observed during the exposure period. Observations after four hours included all animals.
- Frequency of weighing: just prior to the inhalation exposure and on Days 7 and 14 or at the time of discovery after death
- Necropsy of survivors performed: yes
- Clinical signs including body weight: yes

Statistics:

None

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

1.975 mg/L air

Based on:

test mat.

95% CL:

1.433 - 2.722

Exp. duration:

4 h

Remarks on result:

other: Mortality occurred at the mid and high concentration levels of 1.45 and 2.69 mg/L air, respectively.

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

1.479 mg/L air

Based on:

test mat.

95% CL:

0.748 - 2.924

Exp. duration:

4 h

Remarks on result:

other: Mortality occurred at the mid and high concentration levels of 1.45 and 2.69 mg/L air, respectively.

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.717 mg/L air

Based on:

test mat.

95% CL:

1.267 - 2.327

Exp. duration:

4 h

Remarks on result:

other: both sexes combined

Mortality:

- 0.523 mg/L: no mortality observed
- 1.45 mg/L: 1/5 males died, 3/5 females died
- 2.91 mg/L: 4/5 males died, 4/5 females died

Clinical signs:

other: clinical signs of toxicity in males and females almost included nasal discharge, salivation, lacrimation, piloerection, ptosis, and decreased activity; for details, please refer to "any other Information on results incl. tables", and to Attachment 2.

Body weight:

- 0.523 mg/L: all animals achieved body weight gains as expected during the 14 day observation period.
- 1.45 mg/L: surviving animals achieved body weight gains as expected over the 14 day observation period despite of a lost in weight noticed during the first week.
- 2.69 mg/L: the 2 surviving animals achieved body weight gains as expected over the 14 day observation period despite of a lost in weight noticed during the first week..

Summarized results can be found in Attachment 3.

Gross pathology:

- 0.523 mg/L: No pathological findings were reported.
- 1.45 mg/L: lungs mottled red (1 male and 3 females); orange and red mucoid material in small intestine (1 male and 2 females)
- 2.69 mg/L: lungs red or dark red (3 males, 3 females); orange mucoid material in small intestine (2 males, 2 females), tan slurry and dark brown slurry in stomach (2 males), gastrointestinal tract empty (1 female), dark red mucoid material in small intestine (1 female)

Summarized results can be found in Attachment 3.

Other findings:

None

Any other information on results incl. tables

Details on clinical signs of toxicity:

- 0.523 mg/L: clinical signs of toxicity for both, males and females, consisted of ptosis, decrease in activity and piloerection; the signs were all reversible.
- 1.45 mg/L: nasal discharge, salivation, lacrimation, piloerection, decrease in activity and ptosis were the more common signs of toxicity seen in males and females at this concentration level.
- 2.69 mg/L: also at this concentration level, the clinical signs of toxicity almost consisted of nasal discharge, salivation, lacrimation, piloerection, decrease in activity and ptosis for both, males and females.
Please also refer to Attachment 2.

 

 

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The study was conducted under GLP conditions, according to U.S. EPA guidelines No. 81-3, which in principle is similar to the OECD test guideline 403. The animals were exposed for 4 hours to the test item as aerosol. The resulting combined LC50 for male and female rats was set at 1.72 mg/L air. Accordingly, the substance is to be classified in Cat 4 according to the criteria of the the CLP Regulation (EU) No. 1272/2008.