Farnesol

Endpoint summary

Description of key information

Acute oral toxicity: The oral LD50 could not be calculated as there was no effect on mortality in the study. Therefore the oral LD50 in rats is considered to be >20 mL/kg, which, based on a density of 0.888, is equivalent to >17760 mg/kg.

Acute inhalation toxicity: This endpoint is waived as adequate data from acute studies via oral and dermal routes are available.

Acute dermal toxicity: The dermal LD50 could not be calculated as there was no effect on mortality in the study. Therefore the dermal LD50 in rats is considered to be >15000 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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Study not conducted according to regulatory guideline method or GLP, however study is well-designed and well-reported.

Qualifier:

according to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", by the Staff of the Division of Pharmacology, FDA

Version / remarks:

1959

Deviations:

no

Principles of method if other than guideline:

A single dose of the test material was administered orally to groups of 10 Wistar rats (5 males and 5 females) at doses of 10 mL/kg and 20 mL/kg per group; Animals were observed for clinical signs (motor activity, coordination disturbance, piloerection and diarrhoea) and mortality for 7 days after dosing.

Institute Name IBR
Final Report date 00.11.1976
Results acute oral LD50 (rat) > 20 ml/kg (calc.)
Reliability Rel 2
GLP NO
observed, all symptoms reversible within 3 hours. Rel. 2: According to FDA, 1954, but
not GLP, no batch number and no analytical data on purity, probably technically pure
material was tested;

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation:120 to 160 g
- Fasting period before study: 16 hours
- Housing: Individual cages
- Diet (e.g. ad libitum): Laboratory standard diet (Ssniff/Intermast), ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C ± 1 °C
- Humidity (%): 45 - 55 % RH
- Photoperiod (hrs dark / hrs light): 12 hr light photoperiod

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

10mL/kg or 20mL/kg

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days

Preliminary study:

The doses were determined in a range-finding study. A higher dose is not used in the determinative test for volume reasons.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 20 mL/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality was observed at either dose.

Clinical signs:

other: Decreased motor activity, coordination disturbance, piloerection and diarrhoea were observed, however these symptoms were reversible after 3 hours.

Gross pathology:

No pathological changes in cranial, thoracic and abdominal cavities observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 in rat is > 20mL/kg.

Executive summary:

In an acute oral toxicity study, groups of 10 Wistar rats (5 males & 5 females) per group, received doses of 10 and 20 mL test material/kg by gavage and were observed for 7 days thereafter. There were no mortalities or pathologic effects observed. There was decreased motor activity, disturbances of coordination, piloerection and diarrhoea, however all symptoms were reversible within 3 hours. The LD50 was estimated to be > 20 mL/kg. This study is reliable with restrictions (Klimisch 2) as it was conducted according to guideline, however GLP status is unknown.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

17 760 mg/kg bw

Quality of whole database:

One key study is available, which is considered to be reliable with restrictions (Klimisch 2) as it was conducted according to guideline, however GLP status is unknown.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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

Study period:

07 December 1982 - 23 December 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Non-guideline, non-GLP study, however experimental details and results are well-reported.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Acute dermal toxicity was tested in male and female WISW-strain rats. Applications were made on scarified and intact skin and test animals were observed for 14-days for any signs of reaction and mortality.

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: BOR: WISW (substrain SPF TNO)
- Weight at study initiation: 190.0 to 258.0 g for males, 160.0 to 205.0 g for females
- Housing: maximum 5 rats per cage
- Diet (e.g. ad libitum): Pellets with added vitamins
- Water (e.g. ad libitum): Aqua fontana fit for human consumption, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2 °C
- Humidity (%): 45 to 55%
- Photoperiod (hrs dark / hrs light): 12 hour photoperiod with fluorescent lighting (120 Lux)

IN-LIFE DATES: From: 7/12/1982 To: 23/12/1982

Type of coverage:

other: Scarified and intact skin

Vehicle:

other: white Vaseline

Details on dermal exposure:

TEST SITE
- Area of exposure: Clipped area (8 x 5 cm) on the back of each test animal; one group was abraded with a clean clipper blade to penetrate the horny layer of the epidermis without causing bleeding, while the other group was left intact.
- Type of wrap if used: Dose secured for 24 hours with gauze pads and plastic material

REMOVAL OF TEST SUBSTANCE
- Washing: Substance removed with wet disposable gauze
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 2.40 to 3.88 g
- Concentration: 10%
- Constant volume or concentration used: Constant concentration, the application sample was weighed per animal
- For solids, paste formed: yes

Duration of exposure:

24h

Doses:

10%

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical-toxicological signs (modified Irvin-Screening) recorded at 2, 4, 24, 48 and 72 hrs and 7 and 14 days after application; body weight recorded at the start and end of experiment on the surviving animals.
- Necropsy of survivors performed: yes, immediately after all mortalities and upon study completion for the survivors
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Skin alterations (modified Draize-Scheme) recorded at 24 hours and 3, 7 and 14 days after application

Preliminary study:

Pairs of female rats were scarified and administered with 5 and 15 g/kg bodyweight.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

No mortalities were observed

Clinical signs:

other: The sample did not induce any clinical-toxicological symptoms and no skin alternations were observed.

Gross pathology:

No gross pathological findings were recorded.

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of 10% farnesol in Vaseline was determined to be > 15 g/kg bodyweight for rat.

Executive summary:

The acute dermal toxicity of 10% farnesol in Vaseline was tested in male and female WISW rats. A single dose of 15 g/kg bodyweight was applied on scarified and intact skin of the test animals and secured for 24 hours. Mortality, clinical signs of toxicity, changes in bodyweight, skin alterations and gross pathology were observed for 14 days following application. No mortalities were observed and the dermal LD50 was determined to be > 15 g/kg bodyweight. This study is reliable with restrictions (Klimisch 2) as it was well-designed and well-reported, however was not performed according to any specific guideline or to GLP.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

15 000 mg/kg bw

Quality of whole database:

One key study is available, which is considered to be reliable with restrictions (Klimisch 2) as no guideline or GLP compliance was reported, however the experimental design and reporting were adequate.

Additional information

Acute oral toxicity: In the key acute oral toxicity study, groups of 10 Wistar rats (5 males & 5 females) per group, received doses of 10 and 20 mL test material/kg by gavage and were observed for 7 days thereafter (1976). There were no mortalities or pathologic effects observed. There was decreased motor activity, disturbances of coordination, piloerection and diarrhoea, however all symptoms were reversible within 3 hours. The LD50 was estimated to be > 20 mL/kg. With relative density measured at 0.888 g/cm3, the oral LD50 was estimated to be > 17.76 g/kg. This study is reliable with restrictions (Klimisch 2) as it was conducted according to guideline, however GLP status is unknown.

Acute inhalation toxicity: This endpoint is waived as adequate data from acute studies via oral and dermal routes are available. Exposure to humans via inhalation is not likely given the low vapour pressure of the substance.

Acute dermal toxicity: In the key acute dermal toxicity study, a single dose of 15 g/kg bodyweight (10% farnesol in vaseline) was applied on scarified and intact skin of male and female WISW rats and secured for 24 hours (1983). Mortality, clinical signs of toxicity, changes in bodyweight, skin alterations and gross pathology were observed for 14 days following application. No mortalities were observed and the dermal LD50 was determined to be > 15 g/kg bodyweight. This study is reliable with restrictions (Klimisch 2) as it was well-designed and well-reported, however was not performed according to any specific guideline or to GLP.

Justification for classification or non-classification

The two key studies for the acute toxicity endpoint were performed in rats by either the oral or dermal routes of administration. Both studies were considered to be of robust design and well reported and assigned a Klimisch score of 2 (reliable with restrictions). As the acute oral and dermal studies resulted in predicted LD50 levels in excess of the 2000 mg/kg limit dose, it was concluded that farnesol is not classified for acute toxicity according to the CLP Regulation (EC) No 1272/2008.