2,6-dibromo-4-cyanophenyl octanoate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 Jul - 30 Aug 1991

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:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Version / remarks:

adopted 1984

Deviations:

not specified

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 2009

Deviations:

yes

Remarks:

limited information on materials provided (housing conditions not specified, no details on exposure provided); minor methodological deviatios (temperature in exposure chamber too high, body weight was only weekly noted)

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 octanoate

EC Number:

216-885-3

EC Name:

2,6-dibromo-4-cyanophenyl octanoate

Cas Number:

1689-99-2

Molecular formula:

C15H17Br2NO2

IUPAC Name:

2,6-dibromo-4-cyanophenyl octanoate

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., Texas, USA
- Females nulliparous and non-pregnant: yes
- Age at study initiation:
young adult
- Weight at study initiation:
226 - 300 g (males) and 188 - 245 g (females)
- Housing:
1-3 animals per cage (males separate from females) and during exposure period individually 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 specified
- Humidity (%): not specified
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): not specified

IN-LIFE DATES: From: 29 Jul To: 30 Aug 1991

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

not specified

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

>= 1.84 - <= 2.33 µm

Geometric standard deviation (GSD):

>= 1.875 - <= 2.067

Remark on MMAD/GSD:

0.379 mg/L test substance: MMAD = 1.838 µm and GSD = 2.042
0.583 mg/L test substance: MMAD = 1.976 - 1.986 µm and GSD = 1.968 - 1.889
0.723 mg/L test substance: MMAD = 1.938 µm and GSD = 1.890
0.733 mg/L test substance: MMAD = 1.990 - 1.965 µm and GSD = 1.875 - 2.067
1.17 mg/L test substance: MMAD = 2.326 µm and GSD = 1.892

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:
dynamic flow inhalation chamber
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber:
not specified
- Source and rate of air (airflow):
dried, heated and filtered air, 68 L/min
- Method of conditioning air:
not specified
- System of generating particulates/aerosols:
The aerosol was generated by pumping the test material into a pressure operated Spraying System Company air atomizer (1/4 JSS) and then elutriating the resulting aerosol through a baffling chamber. The concentrated aerosol was then diluted with dried, heated and filtered air and drawn into the exposure chamber.
- Method of particle size determination:
Particle size was determined at least once during each exposure, using an Andersen cascade impactor, at a rate of 28.3 L/min for a duration of 1 - 10 min.
- Treatment of exhaust air:
not specified
- Temperature, humidity, pressure in air chamber:
27.2 - 28.9 °C, 56 - 72% relative humidity, oxygen content was at least 19%

TEST ATMOSPHERE
- Brief description of analytical method and equipment used:
Analytical determination was made using a Tracor Model 560 gas chromatograph.
- Samples taken from breathing zone: yes
- Time needed for equilibrium of exposure concentration before animal exposure
: 13.5 min

TEST ATMOSPHERE (if not tabulated)
Please refer to "Remark on MMAD/GSD"

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

nominal concentrations: 8.75, 7.74, 2.89, 7.70 and 11.7 mg/L
analytical concentrations: 0.379, 0.583, 0.723, 0.733 and 1.17 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: frequently on the day of exposure and at least once daily thereafter
- Frequency of weighing: prior to the inhalation exposure and on Days 7 and 14, or at the time of discovery after death
- Necropsy of survivors performed: yes

Statistics:

LC50 was calculated according to the method of Litchfield and Wilcoxon (1949).

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

0.809 mg/L air (analytical)

Based on:

test mat.

95% CL:

>= 0.612 - <= 1.07

Exp. duration:

4 h

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

0.721 mg/L air (analytical)

Based on:

test mat.

95% CL:

>= 0.589 - <= 0.883

Exp. duration:

4 h

Mortality:

0.379 mg/L test substance: 0/5 males and 0/5 females
0.583 mg/L test substance: 0/5 males and 2/5 females
0.723 mg/L test substance: 1/5 males and 2/5 females
0.733 mg/L test substance: 4/5 males and 2/5 females
1.17 mg/L test substance: 4/5 males and 5/5 females
Death occurred within 4.5 h to 3 days following exposure to the test substance.
For details, please refer to attachment 1.

Clinical signs:

other: decreased activity, lacrimation, nasal discharge, piloerection, polyuria, ptosis and salivation.

Remarks:

For details, please refer to attachment 2.

Body weight:

Animals that died following exposure to the test item, showed a weight loss of up to 26% when compared to the body weight at study initiation (Day 0). For details, please refer to attachment 1.

Gross pathology:

Gross necropsy findings included signs of nasal discharge, polyuria and salivation, discoloration of the contents of the gastrointestinal tract, gastrointestinal tract distended with gas, discolored fluid of the thoracic cavity, discoloration of the liver and lungs and swollen lungs. For details, please refer to attachment 1.

Other findings:

An attempt was made to reach a concentration of 5.0 mg/L with 25% of particles under 1 µm. However, due to the nature of the test material, a test level could not be generated containing at least 25% of particles under 1 µm to calculate an LC50 value.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The study was performed according to EPA OPP 81-3 (acute inhalation toxicity) and GLP. Therefore, the study is considered to be valid and reliable. Under the conditions of the test, the acute inhalation LC50 value was determined to be 0.81 mg/L for male and 0.72 mg/L for female rats. According to criteria of the CLP Regulation (EU) No. 1272/2008, classification of the test item for acute inhalation toxicity category 3 (H331) is warranted.