Farnesol

Endpoint summary

Description of key information

Skin irritation / corrosion: Mean individual values of 2.67, 2.67 and 2.0 were observed for erythema and mean individual values of 1.33, 3.0 and 2.33 were observed for oedema in rabbits. Very slight to severe erythema and oedema were observed in all animals. Additionally, scale formation was observed in two animals and in duration of the treated skin area with bloody fissures was seen in one animal. The effects in one animal were not fully reversible within 15 days after patch removal.

Eye irritation: The mean individual grades of ocular reactions at 24, 48 and 72 hr post-application were 0.0, 0.0 and 0.0 for corneal opacity, 0.33, 0.67 and 0.0 for iritis, 2.0, 1.0 and 1.0 for conjunctival redness, and 1.0, 0.67 and 0.33 for chemosis. Hyperemia of the iris was observed in two animals. Slight to moderate redness and swelling of the conjunctivae as well as slight to moderate ocular secretion were seen in all animals. All effects were fully reversible within 5 days.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Housing: Individual housing (50 x 45 x 40 cm) in a battery of cages, each equipped with a paper roll disposal system
- Diet (e.g. ad libitum): Pellets with added vitamins, ad libitum
- Water (e.g. ad libitum): Drinking water for human consumption, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3 C
- Humidity (%): 30 to 70 %
- Photoperiod (hrs dark / hrs light): 12 hour photoperiod with artificial lighting (120 lux)

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

15 days post application

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Clipped area (approximately 6 cm2) on the back of each test animal
- Type of wrap if used: Ypsiplast® (Holthaus Medical, Remscheid-Lüttringhausen), held in place by non-irritating tape (Elastoplast®, Beiersdorf AG, Hamburg) and Stuelpa® (P. Hartmann AG, Heidenheim-Brenz)

SCORING SYSTEM:
As per OECD Test Guideline 404
Erytrhema and eschar 0 -4 scale
Oedema 0-4 scale

Animals were examined for signs of erythema and oedema at 60 minutes and 24, 48 and 72 hours after patch removal and once daily thereafter up to 15 days post-application.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 9 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

not fully reversible within: 15 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Scale formation after 6 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 15 days

Remarks on result:

other: Induration after 72 hours, scabbing after 6 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 12 days

Remarks on result:

other: Scale formation after 7 days

Irritant / corrosive response data:

Erythema (very slight to severe) was observed in all animals between 1 h after patch removal and day 7 post application (p.a.). It was still apparent in two animals on day 8 p.a. and in one animal up to the end of the observation period (day 15 p.a.). Oedema (very slight to severe) was observed in all animals up to day 6 p.a., and was still apparent in two animals up to day 11 p.a. and in one animal up to day 15 p.a.

Scale formation was seen from day 6 and day 7 p.a. up to the end of the observation period (day 15 p.a.) in animals no. 1 and 3, respectively.

Additionally, in one animal (no. 2) the treated skin area became indurated from 72 h and up to day 13 p.a. This induration was associated with fissures which were first bloody and then covered with scab. At the days 14 and 15 after patch removal the healing process caused an incipient desquamation of the indurated skin area .

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Mean individual values of 2.67, 2.67 and 2.0 were observed for erythema and mean individual values of 1.33, 3.0 and 2.33 were observed for oedema.

Executive summary:

The test item was assessed in an acute dermal irritation/corrosion test in 3 albino rabbits. Shaved skin was exposed to 0.5 mL of the test article for 4 hours under a semi-occulsive dressing. Animals were examined for signs of erythema and oedema at 60 min, 24, 48 and 72 h after patch removal and thereafter once daily up to day 15 post application. Mean individual values of 2.67, 2.67 and 2.0 were observed for erythema and mean individual values of 1.33, 3.0 and 2.33 were observed for oedema. Very slight to severe erythema and oedema were observed in all animals. Additionally, scale formation was observed in two animals and in duration of the treated skin area with bloody fissures was seen in one animal. The effects in one animal were not fully reversible within 15 days after patch removal. This study is reliable without restrictions (Klimisch 1) as it was conducted according to relevant guidelines and GLP.

As mean values of ≥ 2.3 to ≤ 4.0 for erythema/eschar and oedema were observed in at least 2 of 3 tested animals, the test item is classified a Skin Irritant, Category 2.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Study is siimilar to OECD guideline 406, but not GLP and not sufficient for complete assessment of the endpoint as only a 10% preparation was tested. Study is part of a skin sensitisation study.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Method is similar to OECD 406.

GLP compliance:

not specified

Species:

guinea pig

Strain:

Pirbright-Hartley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 255 g
- Housing: Makrolon III cage (14 x 25 x 42 cm), 2 guinea pigs per cage
- Diet (e.g. ad libitum): Pellets
- Water (e.g. ad libitum): Tap water fit for human consumption, ad libitum
- Acclimation period: approximately 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2 C
- Humidity (%):45 to 55 %
- Photoperiod (hrs dark / hrs light): 12 hour photoperiod with tungsten lighting (120 lux, 4000 K)

IN-LIFE DATES: From: 20/12/1983 To: 7/1/1983

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: White Vaseline

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.05 mL of 1:1 farnesol in 10% white Vaseline in peanut oil for intradermal application, and 0.5 mL for the challenge test

VEHICLE
- Amount(s) applied (volume or weight with unit): 1:1 test preparation in peanut oil for intradermal application and in Vaseline vehicle for topical applications

Duration of treatment / exposure:

48 hours

Observation period:

14 days

Number of animals:

20 animals per treatment

Details on study design:

Three pairs of injections, six injections in total, were made intradermally in the shaved skin: a) 0.05 mL Freund's adjuvant (1: 1 diluted in distilled water), and, b) 0.05 mL farnesol 10 % in white petrolatum (diluted 1: 1 with peanut oil). The day after the first two intradermal injections, the left half of the cropped shoulder region was treated with 10% sodium lauryl sulphate in white petrolatum to cause mild irritation and 6 - 8 hours later the test substance allergen or control substances were applied dermally. The test substance was applied in a 10% emulsion in white petrolatum and the treated area was covered with gauze and Elastoplast.The following day ( = 48 hours after the two intradermal treatments), the dresssing was removed and was followed by the 3rd intradermal injection.

The challenge exposure was carried out as a " closed patch" test 14 days after the last treatment using three different concentrations per animal. The left flank of the animals was shaved the day before the challenge and 0.5 mL of the challenge concentrations were applied in small round patches. The application area was covered with a gauze pad and the trunk was wrapped in a strip of Elastoplast. After 24 hours, the dressing was removed and the test sites were examined (24 hours post application) and then re-examined a day later (48 hours post application).

TEST SITE
- Area of exposure: Shaved area (approximately 8 x 5 cm) on shoulder of test animal
- Type of wrap if used: Gauze and elastoplast

SCORING SYSTEM:
0 = no reaction
0.5 = light, patchy (irregular) erythema
1 = slight, confluent or moderately patchy erythema
2 = moderate erythema
3 = severe erythema or edema

- Positive control: Methyl methacrylate (Merck Schuchard, Hohenbrunn)

Irritation parameter:

overall irritation score

Time point:

48 h

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No primary irritation was observed for test item compared to the control.

Interpretation of results:

study cannot be used for classification

Conclusions:

No irritation was observed in guinea pigs exposed to 10% farnesol in white Vaseline.

Executive summary:

Skin irritation was assessed as part of a skin sensitisation study in guinea pigs. The test item at 10% concentration in white Vaseline was applied in a series of intradermal and topical doses, followed by a challenge test 14 days later. Two pairs of intradermal injections of a 1:1 solution of the test item in peanut oil, with and without adjuvant, were made in the shoulder of the guinea pigs. A day later, sodium lauryl sulfate in a white Vaseline vehicle was topically applied to the injection sites to induce a slight irritation and a topical application of test item at 10% concentration in white Vaseline positive control or negative control was applied six to eight hours later. The topical application was secured with dressing and removed the next day, at which point a third pair of injections was made. Fourteen days after the last injection, the challenge exposure was carried out as a closed patch test with 2.5, 5.0 and 10% test item concentration in white Vaseline. The exposure area was occluded for 24 hours after application and skin irritation and sensitisation were assessed at 24 and 48 hours after the challenge application. No irritation was observed with 10% test item concentration in white Vaseline. This study is reliable with restrictions (Klimisch 2) as it was not conducted in accordance with any particualr guideline or GLP and quantitative results are not reported for skin irritation.

Reference 3

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: Individual housing (50 x 45 x 40 cm. x B x H) in a battery of cages, each equipped with a paper roll disposal system
- Diet (e.g. ad libitum): Pellets, ad libitum
- Water (e.g. ad libitum): Drinking water fit for human consumption, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3C
- Humidity (%):30 to 70 %
- Photoperiod (hrs dark / hrs light): 12 hour photoperiod with artificial lighting (120 lux)

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0. 1mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

Ocular reactions were assessed 1, 24, 48 and 72 h after treatment and thereafter once daily up to day 5 post application.

Observation period (in vivo):

5 days

Number of animals or in vitro replicates:

3

Details on study design:

The test item was introduced into the conjunctival sac of the left eye and the untreated right eye served as control. There was no removal of the test item.

SCORING SYSTEM:
Grading of ocular lessions as per EEC directive 93/21/EEC of April 27, 1993:
Corneal Opacity (0-4 scale)
Irititis (0-2 scale)
Conjunctival redness (0-3 score)
Chemosis (0-4 scale)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: Hyperemia of the iris observed

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible within: 3 days

Remarks on result:

other: Hyperemia of the iris observed

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 5 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 3 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 3 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 3 days

Remarks on result:

other: Secretion observed with chemosis

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: Secretion observed with chemosis

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: Secretion observed with chemosis

Irritant / corrosive response data:

Hyperemia of the iris was observed at 1 and 24 hours post application (p.a.) in animal no. 1 as well as at 24 and 48 hours p.a. in animal no. 2. Moderate redness of the conjunctivae was seen 1 hour p.a. in all animals. Redness was still apparent up to day 4 p.a. in animal no. 1 and up to 48 hours p.a. in animals no. 2 and 3. Swelling of the conjunctivae (slight to moderate) was observed in all animals 1 and 24 hours p.a. and was still apparent in animal no. 1 up to day 4 p.a. and in animal no 3 at 48 hours p.a. Additionally, slight to moderate ocular secretion was seen between 1 and 48 hours p.a. in all animals. The observed findings were reversible within 5 days p.a.

Other effects:

No other toxic effects were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The mean individual grades of ocular reactions at 24, 48 and 72 hr post-application were 0.0, 0.0 and 0.0 for corneal opacity, 0.33, 0.67 and 0.0 for iritis, 2.0, 1.0 and 1.0 for conjunctival redness, and 1.0, 0.67 and 0.33 for chemosis. All effects were fully reversible within 5 days.

Executive summary:

The eye irritation/corrosion potential of the test item was tested on 3 albino rabbits. In each animal, 0.1 mL of the test article was introduced into the conjunctival sac of one eye and the untreated eye served as control. Both eyes were examined at 24, 48 and 72 h post application (p.a.) and thereafter once daily up to day 5 p.a. Hyperermia of the iris was observed in two animals. Slight to moderate redness and swelling of the conjunctivae as well as slight to moderate ocular secretion were seen in all animals. The mean individual grades of ocular reactions at 24, 48 and 72 hr post-application were 0.0, 0.0 and 0.0 for corneal opacity, 0.33, 0.67 and 0.0 for iritis, 2.0, 1.0 and 1.0 for conjunctival redness, and 1.0, 0.67 and 0.33 for chemosis. All effects were fully reversible within 5 days. No other toxic effects were observed. The test substance is therefore not classified as an eye irritant according to CLP Regulation (EC) No 1272/2008 (8th Adaptation to Technical Progress). This study is reliable without restriction (Klimisch 1) as it was conducted according to guideline and GLP.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study is not conducted according to OECD protocol and predates GLP, but is well-documented.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Draize test, method similar to OECD 405. Based on protocol of "Appraisal of the safety of chemicals in foods, drugs and cosmetics", by the staff of the Division of Pharmacology, FDA, evaluated according to the method of Draize, 1959.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.4 to 2.6 kg
- Housing: Individual cages
- Diet (e.g. ad libitum): Standard diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Fasting period: 16 hrs

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C
- Humidity (%): 50 to 60 %
- Photoperiod (hrs dark / hrs light): 12 hour photoperiod

Vehicle:

other: soy bean oil

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of 0.3 % solution (0.3mg test material) in soybean oil
- Concentration (if solution): 0.3%

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.1 mL of 0.3 % solution in soybean oil

Observation period (in vivo):

up to 7 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none

Ocular changes were assessed after 60 and 120 minutes, after 8, 24, 48 and 72 hours, as after 4, 5, 6 and 7 days. Bodyweight was recorded at the start and end of the study.

TOOL USED TO ASSESS SCORE: 2% sodium fluorescein and UV lighting

SCORING SYSTEM:
As per Draize 1959. The total score for the eye is the sum of all points for the cornea, iris and conjunctiva.
Cornea opacity (0 to 4 scale)
Size of affected area (1 to 4 scale)
Iris (0 to 2 scale)
Conjunctival redness (0 to 3 scale)
Conjunctival chemosis (0 to 4 scale)
Conjunctival secretion (0 to 3 scale)

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No effects on the cornea or iris were observed in any of the animals. Conjunctival redness (max score 1), chemosis (max score 2) and secretion (max score 2) were observed in all animals and effects were fully reversible within 24 hours. The mean of the total score (sum of all points for the cornea, iris and conjunctiva) were 7.33 at 1 hour, 10 at 2 hours and 10 at 8 hours. All effects were fully reversible within 24 hours.

Interpretation of results:

study cannot be used for classification

Conclusions:

A 0.3% solution of farnesol in soybean oil was not irritating to the rabbit eye.

Executive summary:

A single dose of 0.3% test item in soybean oil was instilled into one rabbit eye, with the other eye acting as control. Eyes were evaluated after 1 ,2, 8, 24, 48 and 72 hours and at 4, 5, 6, and 7 days post application for corneal, iris and conjunctival effects according to the scoring system of Draize (1959). Conjunctival redness, chemosis and secretion were observed in all animals and effects were fully reversible within 24 hours. The mean of the total score (sum of all point for the cornea, iris and conjunctiva) was 7.33 at 1 hour, 10 at 2 hours and 10 at 8 hours. This study is reliable with restriction (Klimisch 2) as it was not conducted according to guideline or GLP, but was well-designed and well-reported.

Using the criteria of Draize (1959), a 0.3% solution of 2,6,10-Dodecatrien-1-ol, 3,7,11-trimethyl- in soybean oil is considered to be not irritating to the rabbit eye.

Reference 3

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion: In the key skin irritation study, rabbits were shaved and exposed to 0.5 mL of the test article for 4 hours under a semi-occlusive dressing (1995). Animals were examined for signs of erythema and oedema at 60 min, 24, 48 and 72 h after patch removal and thereafter once daily up to day 15 post application. Mean individual values of 2.67, 2.67 and 2.0 were observed for erythema and mean individual values of 1.33, 3.0 and 2.33 were observed for oedema. Very slight to severe erythema and oedema were observed in all animals. Additionally, scale formation was observed in two animals and in duration of the treated skin area with bloody fissures was seen in one animal. The effects in one animal were not fully reversible within 15 days after patch removal. This study is reliable without restrictions (Klimisch 1) as it was conducted according to relevant guidelines and GLP.

A supporting study is available where skin irritation was assessed as part of a skin sensitisation study in guinea pigs (1983). The test item at 10% concentration in white Vaseline was applied in a series of intradermal and topical doses, followed by a challenge test 14 days later. Two pairs of intradermal injections of a 1:1 solution of the test item in peanut oil, with and without adjuvant, were made in the shoulder of the guinea pigs. A day later, sodium lauryl sulfate in a white Vaseline vehicle was topically applied to the injection sites to induce a slight irritation and a topical application of test item at 10% concentration in white Vaseline positive control or negative control was applied six to eight hours later. The topical application was secured with dressing and removed the next day, at which point a third pair of injections was made. Fourteen days after the last injection, the challenge exposure was carried out as a closed patch test with 2.5, 5.0 and 10% test item concentration in white Vaseline. The exposure area was occluded for 24 hours after application and skin irritation and sensitisation were assessed at 24 and 48 hours after the challenge application. No irritation was observed with 10% test item concentration in white Vaseline. This study is reliable with restrictions (Klimisch 2) as it was not conducted in accordance with guidelines analyzing irritation or GLP and quantitative results are not reported for skin irritation.

Eye irritation: In the key study, the eye irritation potential of the test item was tested on 3 albino rabbits (1995). In each animal, 0.1 mL of the test article was introduced into the conjunctival sac of one eye and the untreated eye served as control. Both eyes were examined at 24, 48 and 72 h post application (p.a.) and thereafter once daily up to day 5 p.a. Hyperemia of the iris was observed in two animals. Slight to moderate redness and swelling of the conjunctivae as well as slight to moderate ocular secretion were seen in all animals. The mean individual grades of ocular reactions at 24, 48 and 72 hr post-application were 0.0, 0.0 and 0.0 for corneal opacity, 0.33, 0.67 and 0.0 for iritis, 2.0, 1.0 and 1.0 for conjunctival redness, and 1.0, 0.67 and 0.33 for chemosis. All effects were fully reversible within 5 days. No other toxic effects were observed. This study is reliable without restriction (Klimisch 1) as it was conducted according to guideline and GLP.

A supporting study is available where a single dose of 0.3% test item in soybean oil was instilled into one rabbit eye, with the other eye acting as control (1976). Eyes were evaluated after 1, 2, 8, 24, 48 and 72 hours and at 4, 5, 6, and 7 days post application for corneal, iris and conjunctival effects according to the scoring system of Draize (1959). Conjunctival redness, chemosis and secretion were observed in all animals and effects were fully reversible within 24 hours. The mean of the total score (sum of all point for the cornea, iris and conjunctiva) was 7.33 at 1 hour, 10 at 2 hours and 10 at 8 hours. Using the criteria of Draize (1959), a 0.3% solution of the test item in soybean oil is considered to be not irritating to the rabbit eye. This study is reliable with restriction (Klimisch 2) as it was not conducted according to guideline or GLP, but was well-designed and well-reported.

Justification for classification or non-classification

Two key in vivo studies (Klimisch 1) in rabbits are available for classification of skin irritation and eye irritation according to CLP Regulation (EC) No 1272/2008 (8th Adaptation to Technical Progress). As mean values of ≥2.3 to ≤4.0 for erythema/eschar and oedema were observed in at least 2 of 3 tested animals, the test item is classified a Skin Irritant, Category 2. As the mean scores were <1 for corneal opacity, <1 for iritis, <2 for conjunctival redness and <2 for chemosis in at least 2 of 3 tested animals, the test item is not classified as an eye irritant.