Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10/18/2006 - 02/13/2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP conducted study conducted according to OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class (ATC) Method)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Remarks:
OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class (ATC) Method)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Pale yellow liquid.100% pure

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Upon receipt, Sprague-Dawley Derived Crl:CD (SD) IGS BR rats were randomly housed individually in hanging stainless steel wire mesh cages. Following acclimation to laboratory conditions (1 week) and pre-test physical examinations, 10 rats (5 males/5 females)were assigned to the study via computer generated random numbers. Certified Rodent Diet 5002 Laboratory Chow (PMI Nutrition Int.) and tap water were made available ad libitum except when withheld during the 4 hour exposure. Fresh feed was presented weekly. A 12-hour light/dark cycle was provided. Daily average temperature range was 19-21degrees C and Relative Humidity ranged from 25-54%. Body weights at time of exposure averaged for males 273 g (267-283 g range) and for females was 225 g (219-234 g range). During exposure the animals were individually housed in polycarbonate tubes attached to a cast aluminum and alloy 40-Liter nose-only exposure chamber. The chamber environment was monitored for temperature, relative humidity (RH) and airflow rate every half-hour during exposure. Temperature was 20ºC and RH ranged within 46 – 54%.

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Exposure of the test animals was conducted with a 40-liter nose-only cast aluminum and alloy chamber. Animals were individually housed in polycarbonate tubes attached to the chamber in manifold fashion. The chamber was operated in a dynamic mode with total airflow through the chamber of 22 liters per minute as measured by a calibrated flowmeter. Test material was used as received and was generated as respirable aerosol in the breathing zone of the animals. Pre-study trials were performed to evaluate the optimal set of conditions and equipment to generate a stable atmosphere at the targeted exposure level. The chamber size and airflow rate were considered adequate to maintain an oxygen level of at least 19%. Thechamber was exhausted using a flowmeter with a built in metering valve and backpressure guage, via plastic tubing. The exhaust was filtered throuigh a series of filter pots.

Analytical verification of test atmosphere concentrations:
yes
Remarks:
Gravimetrically each hour of exposure; Particle size distribution measurements resulte in an average mass median aerodynamic diameter of 2.41 µm with an average geometric standard deviation of 2.12 µm.
Duration of exposure:
ca. 4 h
Concentrations:
Average gravimetric exposure concentration of 5.5 mg/L (milligrams of test substance/Liter of air) with a range of 5.2 – 5.7 mg/L. A total of 124.1 grams of test substance was used during the exposure, resulting in a nominal concentration of 23 mg/L. Highly respirable particle size distribution measurements were an average mass median aerodynamic diameter of 2.41 µm with an average geometric standard deviation of 2.12 and 12% of particles ≤ 1.0 µm, 75% of particles ≤ 4.0 µm and 97% of particles ≤ 10 µm.
No. of animals per sex per dose:
5 animals per sex, per dose.
Control animals:
no
Details on study design:
Isodecyl benzoate was administered as a liquid aerosol to one group of Sprague-DawleyCD rats (5/sex) at a target concentration of 5.0 mg/L via nose-only exposure. The exposure levels were determined gravimetrically during each hour of exposure as were particle size distribution. During the exposure, animals were observed for gross signs of toxicological and pharmacological effects every 15 minutes during the first hour of exposure and hourly through the duration of exposure. Detailed observations were performed on all animals just prior to exposure, immediately upon removal from the exposure chamber, hourly for two hours post- exposure, and once daily thereafter. Body weight measurements were obtained just prior to exposure and weekly thereafter. After a 14-day post-exposure observation period, all animals were sacrificed. Gross postmortem examinations were performed on all animals. The external surface, as well as the thoracic, abdominal and cranial cavities and their organs and tissues were subject to gross examination.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.5 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: Average gravimetric exposure concentration was 5.5 mg/L. Range was 5.2 to 5.7mg/L air.
Sex:
male
Dose descriptor:
LC50
Effect level:
> 5.5 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: Average gravimetric exposure concentration was 5.5 mg/L. Range was 5.2 to 5.7mg/L air.
Sex:
female
Dose descriptor:
LC50
Effect level:
> 5.5 mg/L air (analytical)
Exp. duration:
4 h
Remarks on result:
other: Average gravimetric exposure concentration was 5.5 mg/L. Range was 5.2 to 5.7mg/L air.
Mortality:
There were no treatment-related deaths in the study.
Clinical signs:
Labored breathing was noted in 2 animals during the 4th hour of the exposure period. All other animals were unremarkable for test-substance effect during exposure and during the 14-day observation period.
Body weight:
Animals were all weighed just prior to exposure, on day 8 and day 15. All animals gained weight. Mean body weight change from day 1 for males was 46 g (9.4 g S.D.) on day 8; and, 97 g (12.2 g S.D.) on day 15. Mean body weight change from day 1 for females was 14 g (9.1 g S.D.) on day 8; and, 30 g (12.4 g S.D.) on day 15.
Gross pathology:
There were no treatment-related findings in gross pathological evaluations.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: other:
Conclusions:
The acute inhalation LC50 in rats is > 5.5 mg/L.
Executive summary:

Isodecyl benzoate was administered as a liquid aerosol to one group of Sprague-Dawley CD rats (5/sex) at 5.5 mg/L via nose only exposure. The study was conducted according to OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class (ATC) Method).

The exposure levels were determined gravimetrically (5.5 mg/L mean gravimetric exposure concentration) during each hour of exposure as were particle size distributions (particle size distribution measurements resulted in an average mass median aerodynamic diameter of 2.41 µm with an average geometric standard deviation of 2.12). During the exposure, animals were observed for gross signs of toxicological and pharmacological effects every 15 minutes during the first hour of exposure and hourly through the duration of exposure. Detailed observations were performed on all animals just prior to exposure, immediately upon removal from the exposure chamber, hourly for two hours post-exposure, and once daily thereafter. Body weight measurements were obtained just prior to exposure and weekly thereafter. After a 14-day post-exposure observation period, all animals were sacrificed. Gross postmortem examinations were performed on all animals. The external surface, as well as the thoracic, abdominal and cranial cavities and their organs and tissues were subject to gross examination.

There were no treatment-related deaths in the study. Labored breathing was noted in 2 animals during the 4th hour of the exposure period. All other animals were unremarkable for test-substance effect during exposure and during the 14-day observation period. Animals were all weighed just prior to exposure, on day 8 and day 15. All animals gained weight. Mean body weight change from day 1 for males was 46 g (9.4 g S.D.) on day 8; and, 97 g (12.2 g S.D.) on day 15. Mean body weight change from day 1 for females was 14 g (9.1 g S.D.) on day 8; and, 30 g (12.4 g S.D.) on day 15. There were no treatment-related findings in gross pathological evaluations.

In conclusion, Isodecyl benzoate was practically non-toxic by inhalation to rats by nose-only inhalation exposure with a 4 -hour LC 50 greated than 5.5 mg/L (mean gravimetric exposure concentration) for males and females.