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Diss Factsheets

Administrative data

Description of key information

1) Oral LD50 > 5000 mg/Kg  
2) Inhalation LC50 > 2.19 mg/L
3) Dermal LD50 > 5000 mg/Kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8/18/10 - 11/29/10
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, guideline study
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA on 08/03/10 & Taconic Farms, Hudson, NY
- Age at study initiation: The animals were born the week of 06/08/10 and on 06/21/10. First exposure to test subtance was on 8/31/10
- Weight at study initiation: 224 - 259 grams. The weight variation of the animals used did not exceed + 20% of the mean weight of the previously dosed animals. See body weight data summarzied in "administration/exposure" section.
- Housing/Environmental conditions: The animals were identified by cage notation and indelible body marks, and individually housed in suspended stainless steel wire bottom cages. Paper bedding was placed beneath the cages and changed at least three times per week. 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.
- Diet (e.g. ad libitum): Fresh PMI Rat Chow (Diet #5012) was freely available except for 16-20 hours prior to dosing.
- Water (e.g. ad libitum): Available ad libitum


IN-LIFE DATES: From: 8/31/10 To: 9/22/10
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Initially, one rat dosed at 5000 mg/kg. Since the animal survived, two additional animals were dosed at 5000 mg/kg. The rats were observed at 15 minutes, 1, 2 and 4 hours post dose and once daily for 14 days for toxicity and pharmacological effects. All animals were observed twice daily for mortality.

Doses:
5000 mg/kg

No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
-Oral dosing by syringe and dosing needle
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Daily for mortality; twice daily for toxicity and pharmacoligical effects; weighed pre-test, once weekly, and at termination.
- Necropsy of survivors performed: yes
Statistics:
Animal # Dose volume (cc) Body Weight (g) Day 0 Body Weight (g) Day 7 Body Weight (g) Day 14
1 1.7 259 295 295
2 1.5 224 267 253
3 1.5 227 250 252

Mean 237 271 267
Std. Dev 19.4 22.7 24.5



Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
0/3
Clinical signs:
other: -A single instance of anogenital area wetness was noted during the observation period. See "Adminstration/Exposure" for summary table.
Gross pathology:
Normal
Other findings:
No
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Oral LD50 > 5000 mg/Kg
Executive summary:

Initially, one healthy feamle Sprague Dawley rat was dosed orally with farnesane at 5000 mg/kg. Since the animal survived, two additional animals were dosed at 5000 mg/Kg. The rats were observed at 15 minutes, 1, 2, and 4 hours post-dose and once daily for 14 days for toxicity and pharmacological effects. All animals were oberved twice daily for mortality. Body weights were recorded immediately pre-test, weekly, and at termination. All animals were examined for gross pathology. The potential for toxicity was based on the mortality response noted. All animals survived the 5000 mg/kg oral dose. A single instance of wetness of the anogenial rae was noted during the observation period. Body weight changes wer normal in 2/3 animals. one animal lost weight within the last week of observations. Necropsy results were normal.

Conclusion: The LD50 of farnesane is greater than 5000 mg/Kg body weight in female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
Klimisch score of 1

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system 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
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.
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
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. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
2 190 µg/m³ air
Quality of whole database:
Klimisch score of 1

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, guideline study
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals were received from Covance Research Products, Inc., Denver, PA on 08/11/10. Following an acclimation period of at least five days, five healthy male and five healthy, non-pregnant and nulliparous female New Zealand White rabbits were randomly assigned to the treatment group.

TEST ANIMALS
- Source: Covance Research Products, Inc., Denver, PA

- Age at study initiation: The animals were born on 05/01/10. First Exposure was 8/18/10

- Weight at study initiation: The pretest body weight range was 2.1 - 2.9 kg for males and
2.2 - 2.5 kg for females. The weight variation of the animals used did not exceed + 20% of the mean weight.

- Housing: The animals were identified by cage notation and a uniquely numbered metal eartag and housed 1/cage in suspended wire cages. Paper bedding was placed beneath the cages and changed at least three times/week. The animal room, reserved exclusively for rabbits on acute tests, was temperature controlled, had a 12 hour light/dark cycle, and was kept clean and vermin free.

- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow (Diet #5321) was provided daily.

- Water (e.g. ad libitum): Ad libitum

- Acclimation period: At least 5 days

IN-LIFE DATES: From: 8/18/10 To: 9/1/10
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Site Preparation
The day prior to application of the test article, the dorsal area of the trunk of each animal was clipped free of hair. The prepared site was approximately 10% of the body surface and remained intact.

Dosing
A single dose of the test article was applied to the prepared site, over a 4-ply porous gauze dressing measuring 10 x 15 cm at a dose level of 5000 mg/kg. The dose was based on the sample weight as calculated from the specific gravity. The torso was wrapped with plastic sheeting in a semi-occlusive manner, which was secured with non-irritating tape. The test article remained in contact with the skin for 24 hours at which time the wrappings were removed. Residual test article was removed by gently washing with distilled water.

- Amount(s) applied (volume or weight with unit) are summarzed below in "Results and Discussion" table

Duration of exposure:
24 hours
Doses:
5000 mg/kg
No. of animals per sex per dose:
5 males at 5000 mg/kg and 5 females at 5000 mg/kg
Control animals:
not required
Details on study design:
Five healthy male and five healthy female New Zealand White rabbits were dosed dermally with Farnesane CAS# 3891-98-3, Lot# AMD_072010 at 5000 mg/kg of body weight. The test article was kept in contact with the skin for 24 hours. Dermal responses were recorded at 24 hours postdose and on days 7 and 14. Animals were observed for toxicity, mortality and pharmacological effects at 1, 2 and 4 hours postdose and once daily for 14 days. Body weights were recorded pretest, weekly and at termination. All animals were examined for gross pathology.
Statistics:
Body weight data is summarized in "Results and Discussion"
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
0/10
Clinical signs:
other: One male and one female were noted with soiling of the anogenital area between days 1 and 3. There were no other abnormal physical signs noted during the observation period. Skin reactions were absent to well defined for erythema and absent to slight f
Gross pathology:
Necropsy results were normal.
Interpretation of results:
other: Not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
Dermal LD50 in rabbits > 5000 mg/Kg
Executive summary:

Objective: To determine the potential for toxicity of the test article when applied dermally. This study was designed to comply with the standards set forth in EPA Health Effects Testing Guidelines, OPPTS 870.1200, final guideline, August 1998.

 

Method Synopsis: Five healthy male and five healthy female New Zealand White rabbits were dosed dermally with farnesane CAS# 3891-98-3 at 5000 mg/Kg of body weight. The test article was kept in contact with the skin for 24 hours. Dermal responses were recorded at 24 hours post-dose and on days 7 and 14. Animals were observed for toxicity, mortality and pharmacological effects at 1, 2 and 4 hours postdose and once daily for 14 days. Body weights were recorded pretest, weekly and at termination. All animals were examined for gross pathology. 

 

Summary: All animals survived the 5000 mg/Kg dermal application.

 

One male and one female were noted with soiling of the anogenital area between days 1 and 3. There were no other abnormal physical signs noted during the observation period.

 

Skin reactions were absent to well defined for erythema and absent to slight for edema at 24 hours. On day 7, flaking skin was noted in one animal and no other skin reactions were noted. On day 14, skin reactions were absent.

 

Body weight changes were normal.

 

Necropsy results were normal.

 

Conclusion: The dermal LD50 of Farnesane CAS# 3891-98-3 is greater than 5000 mg/Kg of body weight. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
Klimisch score of 1.

Additional information

Both the acute oral and acute dermal studies show no toxic effects at the limit dose tested - 5000 mg/Kg.

The maximum concentration tested for inhalation toxicity was 2.19 mg/L, which is the maximum dose achievable with an aerosol of MMAD of 0.99 µm (geometric standard deviation 2.69 mm).


Justification for selection of acute toxicity – oral endpoint
Guideline study conducted according to GLP

Justification for selection of acute toxicity – inhalation endpoint
Guideline study conducted according to GLP

Justification for selection of acute toxicity – dermal endpoint
Guideline study conducted according to GLP

Justification for classification or non-classification

Does not meet criteria for toxicity as presented in "Guidance on the Application of the CLP Criteria Guidance to Regulation (EC) No 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures" Version 2.0, April 2012