Registration Dossier

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:
other: GLP; guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report):Farnesane

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms, Inc., Hudson, NY
- Age at study initiation: The animals were born on 06/21/10 & 06/28/10. First exposure occured 9/3/10.
- Weight at study initiation: The pretest body weight range was 309 - 337 grams for males and 221 - 245 grams for females. The weight variation of the animals used did not exceed 20% of the mean weight.
- Housing: Animals were identified by cage notation and indelible tail marks. The animals were housed 1/cage in suspended cages. Paper bedding was placed beneath the cages and changed at least three times/week
- Diet (e.g. ad libitum): Fresh PMI Rat Chow (Diet #5012) ad libitum except during 4 hour exposure period
- Water (e.g. ad libitum): Ad libitum except during 4 hour exposure period
- Acclimation period:

ENVIRONMENTAL CONDITIONS: The animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a 12 hour light/dark cycle and was kept clean and vermin free.

IN-LIFE DATES: From: 9/3/10 To: 9/17/10

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Remarks:
Whole body with nose oriented toward inlet [see illustration section]. Following exposure, the animals were gently washed with warm tap water to remove any residual test substance from the face and body.
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Glass chamber
- Exposure chamber volume: 100 Liter
- Method of holding animals in test chamber:
A 100 liter dynamic glass chamber designed to insure uniform spatial distribution of aerosols and which permitted continuous observation during exposure was used. The chamber was partitioned internally with wire screening into a total of ten non-restraining cubicles. One animal was placed in each cubicle.

- Source and rate of air: The airflow through the chamber was calculated to yield at least 10 to 15 air changes per hour so that adequate oxygen was supplied to the animals. The chamber was maintained at a negative pressure differential to the immediate environment in order to keep the test atmosphere contained.

- Method of conditioning air: Chamber temperature and humidity of air entering the chamber were recorded.

- System of generating particulates/aerosols: Farnesane was added from a Harvard Infusion Pump into an atomizing nozzle (Spraying Systems Model 1/8 JBC). The appropriate flow rate was determined pretest. The spray nozzle was powered by pre-filtered compressed air. Nozzle pressure was monitored using a pressure gauge. The exhaust air was passed through filters before entering into a rotameter and vacuum pump.


- Method of particle size determination:

Mass median aerodynamic diameter (MMAD) was calculated pretest and during each exposure period. An 8 stage Andersen cascade impactor was used to determine particle size. Air was drawn through the impactor for ten minutes. The impactor filter paper collection stages were weighed before and after the air sampling to determine the mass collected at each filter paper collection stage. The MMAD was determined graphically using three cycle logarithmic probit paper. The geometric standard deviation was calculated. A pretest MMAD of 4 microns or less was required to ensure that the particles generated during exposure were in the respirable range. Particle size measurements were recorded at least three times during the exposure period. The average particle size was calculated.


- Temperature, humidity, pressure in air chamber:

Time Airflow Temp Negative Pressure Relative Humidity of air entering chamber
(minutes) L/min Degrees C inches H2O %

30 32 (20L/min) 25 0.3 43
60 32 (20L/min) 25 0.3 43
90 32 (20L/min) 25 0.3 43
120 32 (20L/min) 25 0.3 44
150 32 (20L/min) 25 0.3 45
180 32 (20L/min) 25 0.3 44
210 32 (20L/min) 25 0.3 45
240 32 (20L/min) 25 0.3 45



TEST ATMOSPHERE
- Brief description of analytical method used:

The target concentration was determined prior to exposure by determining the best flow rate for generating the desired concentration.

In order to calculate the concentration gravimetrically, the total solid was determined prior to exposure by drying a preweighed sample of the test article for two minutes, reweighing and calculating the total solid: Final weight\Initial weight.

During the exposure, chamber air was drawn through preweighed filters. The filters were removed and reweighed. The actual concentration of the test article was calculated based on the total solid, the amount of test article dispersed and the air flow through the chamber


- Particle size distribution: See attachment to "Background material." Particle size analyses revealed an average mass median aerodynamic diameter of 0.99 micrometers with an average geometric standard deviation of 2.69 micrometers.

- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): See attachment to "Background Material"


Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
2.19 mg/L
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
All rats were monitored during the exposure period, one hour after exposure and once daily thereafter for 14 days for toxicity and pharmacological effects. The rats were observed twice daily for mortality. Body weights were recorded prior to exposure, weekly and at termination. All animals were examined for gross pathology.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 2.19 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
0/10
Clinical signs:
other: TIME PERIODS ANIMAL #/SEX Day 0=Exposure 1/M 2/M 3/M 4/M 5/M 6/F 7/F 8/F 9/F 10/F Day 0- 35 Minutes Day 0- 95 Minutes 1 1 1 1 1 1 1 1 Day 0- 155 Minutes 1 1 1 1 1 1,4 1 1 1 1,4 Day 0- 215 Minutes 1 1 1 1 1 1,4 1 1 1 1,4 Day 0
Body weight:
All weights are in grams

Animal # Sex Day 0 Day 7 Day 14
1 M 324 345 391
2 M 337 363 403
3 M 326 354 400
4 M 331 362 407
5 M 309 321 362
Mean 325 349 393
Std Dev 10.5 17.2 18.1
N = 5 5 5
6 F 233 240 257
7 F 237 238 256
8 F 234 230 247
9 F 245 230 244
10 F 221 226 253
Mean 234 233 251
Std Dev 8.7 5.9 5.7
N = 5 5 5
Gross pathology:
ANIMAL NUMBER/SEX 1/M 2/M 3/M 4/M 5/M 6/F 7/F 8/F 9/F 10/F
Death (D) Sacrifice (S)
OBSERVATION S S S S S S S S S S
Normal X X X X X X X X X X


X = observed
Other findings:
No

Applicant's summary and conclusion

Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Four hour Inhalation LC50 > 2.19 mg/L
Executive summary:

Objective:To provide information on health effects which may arise from short term exposure by the inhalation route. This study was designed to comply with the standards set forth by EPA Health Effects Test Guidelines, OPPTS 870.1300, final guideline, August 1998.

 

Method Synopsis: Five healthy male and five healthy female Sprague Dawley rats were exposed to an aerosol atmosphere of Farnesane CAS# 3891-98-3 at a concentration of 2.19 mg/L for a period of four hours. Chamber temperature, relative humidity of air entering the chamber, chamber air flow and negative pressure were monitored and recorded. All rats were monitored during the exposure period, one hour after exposure and once daily thereafter for 14 days for toxicity and pharmacological effects. The rats were observed twice daily for mortality. Body weights were recorded prior to exposure, weekly and at termination. All animals were examined for gross pathology.

 

The Target Concentration was estimated prior to exposure. Actual concentrations were determined gravimetrically during exposure. Particle size analyses revealed an average mass median aerodynamic diameter of 0.99mm with an average geometric standard deviation of 2.69 mm. 

 

Summary: 

 

All animals survived the four hour 2.19 mg/L exposure.

 

Closed eyes and coating of the fur with test article were noted during the exposure period. Coating of the fur with test article and piloerection were noted through day 3. All animals appeared normal from day 3 through day 14.

 

All body weights were normal.

 

Necropsy results were normal.

 

Conclusion: The LC50 of Farnesane CAS# 3891-98-3 is greater than 2.19 mg/L.