3-methyl-5-phenylpentanol

Endpoint summary

Description of key information

SKIN IRRITATION/CORROSION
Key study:- Levenstein (1975) Skin irritation/corrosion: Not irritating (5 % concentration)
EYE IRRITATION
Key study:- Givaudan (1987) OECD 405 & EU Method B.5: Not irritating (tested on the aldehyde of 3-methyl-5-phenylpentanol)
Supporting study:- Levenstein (1975) Eye irritation (Similar to OECD 405: Not irritating (5 % concentration)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: The study pre-dates GLP and was not performed to a standardised guideline.

Qualifier:

no guideline followed

Principles of method if other than guideline:

The irritation potential of the test substance was examined in three albino rabbits. The animals were prepared prior to treatment by shaving the test area then making several minor abrasions to penetrate the stratum corneum, but not disturb the derma. A further 3 animals were examined with the vehicle. The exposure time was 24 hours, after which the treated area was observed for a further 48 hours.

GLP compliance:

no

Remarks:

study pre-dates GLP inception

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

Not reported

Type of coverage:

occlusive

Preparation of test site:

abraded

Vehicle:

other: Alcohol SDA 39C

Controls:

yes, concurrent vehicle

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): 5%

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL on two test areas

Duration of treatment / exposure:

Not applicable, no washing was performed.

Observation period:

72 hours (in total)

Number of animals:

3 with test substance, 3 with vehicle.

Details on study design:

TEST SITE
- Area of exposure: Posterior
- % coverage: 10 %
- Type of wrap if used: The 2x2 patch area was covered with Webril patches and the entire experimental area sealed with Blenderm Surgical Tape.

SCORING SYSTEM: In accordance with Draize, as described in "Appraisal of the Safety of Chemicals in Food, Drugs and Cosmetics", published by the Association of Food and Drug Officials of the United States.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24 and 72 hours

Score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

No responses observed in the animals treated with the test substance or in the control animals.

Table 1: Results with test material

Erythema and Eschar Formation	Exposure Time (Hours)	Average Exposure Value
Intact skin	24	0
	72	0
Abraded Skin	24	0
	72	0
Sub total		0
Edema formation	Exposure Time (Hours)	Average Exposure Value
Intact skin	24	0
	72	0
Abraded Skin	24	0
	72	0
Sub total		0

Table 2: Vehicle control results

Erythema and Eschar Formation	Exposure Time (Hours)	Average Exposure Value
Intact skin	24	0
	72	0
Abraded Skin	24	0
	72	0
Sub total		0
Edema formation	Exposure Time (Hours)	Average Exposure Value
Intact skin	24	0
	72	0
Abraded Skin	24	0
	72	0
Sub total		0

Interpretation of results:

other: Study not sufficient to form conclusions on the classification of the substance

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The test substance, as submitted, cannot be considered a primary irritant.

Executive summary:

The irritation potential of the test substance was investigated in albino rabbits. The test substance was applied to abraded and non-abraded skin. Observations were performed at 24 and 72 hours and graded in accordance with the method of Draize. Under the conditions of the test, no irritation was observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1987-06-02 to 1987-06-05

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted in accordance with the standardised guidelines OECD 405 and EU method B.5 and performed in line with GLP with a sufficient level of detail to assess the quality of the presented data. The study was performed on a similar substance to 3-methyl-5-phenylpentanol; the test substance in this study is the aldehyde of 3-methyl-5-phenylpentanol and as such is considered to be sufficient for read-across to address the endpoint.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: ENKI-Konjnenfarm, Someren, The Netherlands
- Weight at study initiation:2500-3500 g
- Housing: Housed individually in suspended, galvanised cages fitted with a wire-mesh floor and front.
- Diet: Standard laboratory rabbit diet ad libitum
- Water: Tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3 °C
- Humidity (%): at least 40 %
- Air changes (per hr): ca. 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Observation period (in vivo):

Up to 72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing : The eyes were not washed out after administration of the test substance

SCORING SYSTEM:
CORNEA
- Opacity-degree of density (area most dense taken for reading)
No opacity - 0
Scattered or diffuse areas, details of iris clearly visible - 1
Easily discernible translucent area, details of iris slightly obscured - 2
Opalescent areas, no details of iris visible, size of pupil barely discernible - 3
Opaque, iris invisible - 4

IRIS
Normal - 0
Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive) - 1
No reaction to light, haemorrhage, gross destruction (any or all of these) - 2

CONJUNCTIVAE
- Redness (refers to palpebral and bulbar conjunctivae, excluding cornea and iris)
Vessels normal - 0
Vessels definitely injected above normal - 1
More diffuse, deeper crimson red, individual vessels not easily discernible - 2
Diffuse beefy red - 3

- Chemosis
No swelling - 0
Any swelling above normal (including nictitating membrane) - 1
Obvious swelling with partial eversion of lids - 2
Swelling with lids about half closed - 3
Swelling with lids about half closed to completely closed - 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

4

Reversibility:

other: No effects observed

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

other: 24 hours

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

other: 48 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

Chemosis

Basis:

mean

Time point:

other: 24 hours

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

Chemosis

Basis:

mean

Time point:

other: 48 hours

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

One hour after application, all three animals exhibited slight or moderate redness of the conjunctivae and slight or moderate swelling of the conjunctivae. Slight iritis was observed in one rabbit.

The eye effects had completely reversed in one rabbit at 24 hours, whereas slight redness of the conjunctivae and slight swelling of the conjunctivae persisted in the other two rabbits.

After 48 hours, the irritation had recovered completely in a second rabbit, slight redness of the conjunctivae and slight swelling of the conjunctivae was observed in the remaining rabbit.

After 72 hours, all irritation had resolved in the third rabbit.

Table 1: Results

Rabbit Number	Observation		Observation Time
			1 Hour	24 Hours	48 Hours	72 Hours
4477	Cornea Opacity		0	0	0	0
	Iris		0	0	0	0
	Conjunctivae	Redness	1	0	0	0
		Chemosis	1	0	0	0
4478	Cornea Opacity		0	0	0	0
	Iris		0	0	0	0
	Conjunctivae	Redness	2	1	1	0
		Chemosis	2	1	1	0
4479	Cornea Opacity		0	0	0	0
	Iris		1	0	0	0
	Conjunctivae	Redness	2	1	0	0
		Chemosis	2	1	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the undiluted test material, was considered to be non-irritating in the rabbit eye. All effects observed were mild in nature and were fully resolved by 72 hours.

Executive summary:

The eye irritation potential of the test substance was assessed in an in vivo study with rabbits, conducted to GLP and in accordance with the standardised guidelines OECD 405 and EU method B.5. The study was performed on the aldehyde of 3-methyl-5-phenylpentanol, and is considered a good reflection of the potential effects of this substance. Under the conditions of the test, the test substance was found to be non-irritating. Some mild irritation was noted during the course of the study, however this was mild in nature and any effects observed were fully resolved by the 72 hour observation period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Levenstein (1975) pre-dates GLP and was not performed to a standardised guideline and was assigned a reliability score of 4 in accordance with Klimisch (1997). Under the conditions of the study, in low concentrations, the test substance was found to be non-irritating in rabbits.

Justification for selection of eye irritation endpoint:
The key study Prinsen and van Beek (1987), was submitted to fulfil the data requirements of this endpoint. The study was performed to GLP and in line with the standardised guidelines OECD 405 and EU Method B.5. The study was performed to a good standard and was assigned a reliability score of 2, in accordance with Klimisch (1997), as the study was performed on the aldehyde of 3-methyl-5-phenylpentanol with the results to be used as read-across. The substance was considered sufficiently similar to be representative of the effects of 3-methyl-5-phenylpentanol. Although Levenstein (1975) was performed on 3-methyl-5-phenylpentanol, it was significantly diluted, and it was considered that the Prinsen and van Beek (1987) was a more accurate reflection of the irritation potential of 3-methyl-5-phenylpentanol. Under the conditions of the test, the test substance was found to be non irritating to the rabbit eye.

Levenstein (1975b) was provided as a supporting study. The study pre-dates GLP and was not performed to a standardised guideline although the method was similar to that of OECD 405. The limited detail in the reporting and the concentration used made the study unsuitable for use in classifying the substance. The study was assigned a reliability score of 3 in accordance with Klimisch (1997). Under the conditions of the study, in low concentrations, the test substance was found to be non-irritating in rabbits.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

According to the criteria outlined in Regulation 1272/2008 and Directive 67/548/EEC, the substance is unclassified for skin and eye irritancy.