1-phenylethanol

Endpoint summary

Description of key information

The skin sensitization potential of target chemical 1-phenylethanol was assessed in various experimental studies.Based on the available studies,it can be concluded that the test chemical is unable to cause skin sensitization and thus considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified''.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Data is from peer reviewed journals

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Modified Draize Technique was employed to determine the concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration ( ACC) ] of 1-Phenylethanol

GLP compliance:

not specified

Type of study:

Draize test

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- IUPAC name: 1-phenylethan-1-ol
- Common Name: 1-Phenylethanol
- Mol. formula: C8H10O
- Molecular Weight: 122.166 g/mole
- InChI: 1S/C8H10O/c1-7(9)8-5-3-2-4-6-8/h2-7,9H,1H3
- Smiles: c1(ccccc1)C(C)O
- Substance type: Organic
- Physical state: Clear colourless liquid

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS

- Weight at study initiation: 350 g
- Housing: Housed in wire mesh cages in pairs of the same sex
- Diet (e.g. ad libitum): Pelleted guinea pig diet, cabbage and hay ad libitum
- Water (e.g. ad libitum): water ad libitum

Route:

intradermal

Vehicle:

not specified

Concentration / amount:

0.1 mL at 2.5 X 0.25%(ICC) : 10 guinea pigs

Day(s)/duration:

no data available

Adequacy of induction:

other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC).

No.:

#1

Route:

intradermal and epicutaneous

Vehicle:

not specified

Concentration / amount:

Challenge concentration: 0.1 mL at 0. 25% (ICC) and 30% (ACC): 10 guinea pigs
Re- challenge concentration: 0.1 mL at 0.25%(ICC) and 30% (ACC): 10 guinea pigs

Day(s)/duration:

24 hours

Adequacy of challenge:

other: The concentration giving slight but perceptible irritation with no oedema was selected as the injection challenge concentration (ICC). The highest concentration which caused no irritation was selected as the application challenge concentration (ACC).

No. of animals per dose:

10: 4 males and 6 females

Details on study design:

MAIN STUDY
RANGE FINDING TESTS: For each test material preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing.


A. INDUCTION EXPOSURE: Intradermal
- No. of exposures:4
- Exposure period: No Data Available
- Test groups:10 guinea pigs
- Control group: No Data Available
- Site: 4 sites, 2 auxillary and 2 inguinal lymph nodes
- Frequency of applications:1
- Duration: No Data Available
- Concentrations: 0.1 mL at 2.5 X 0.25% (ICC)

B. CHALLENGE EXPOSURE: Intradermal and Epicutaneous
- No. of exposures:1
- Day(s) of challenge: Fourteen days later, challenge test was performed
- Exposure period:24 hours
- Test groups:10 guinea pigs
- Control group: No Data Available
- Site: onto the shaved flank in a small circular area
- Concentrations: 0.1 mL at 0.25% (ICC) and 30%(ACC).
- Evaluation (hr after challenge):24 hours

C. RECHALLENGE EXPOSURE
- No. of exposures:1
- Day(s) of challenge: 7 Days Later , rechalleange test was performed.
- Exposure period: No Data Available
- Test groups:10 animal
- Control group: 4 animal (same sex)
- Site: Intradermally and topically on opposite flanks
- Concentrations: 0.1 mL at 0.25% (ICC) and 30% (ACC).
- Evaluation (hr after challenge): No Data Available

-Other:

Observations and scoring –
Each injection reaction was given a total score based on size (2 largest diameters), erythema and oedema. Individual reactions were considered positive when their total score was significantly greater than the average total score for control reactions. Application reactions were scored on a 0 to +++ scale. Reactions were examined under a Philips colour-matching unit with 3 Philips 40 W Actinic Blue 05 fluorescent tubes and 3 Philips 40 W White 35 fluorescent tubes.

Challenge controls:

At each challenge with controls, 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally and topically on opposite flanks with 0.1 ml aliquots of test substance at the ICC and ACC respectively.

Positive control substance(s):

not specified

Positive control results:

No data available

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1 mL at 0.25% (ICC) and 30% (ACC).

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No skin sensitization was observed at tested concentrations

Remarks on result:

no indication of skin sensitisation

Interpretation of results:

other: not sensitizing

Conclusions:

No signs of contact sensitization were observed at 0.25% ICC and 30% ACC concentrations. Hence, 1-phenylethanolThe skin sensitization study of 1 -Phenylethanol was carried out in 10 Inbred Hartley strain albino the guinea pigs of to determine its sensitization potential according modified Draize sensitization test.

Executive summary:

The skin sensitization study of 1 -Phenylethanol was carried out in 10 Inbred Hartley strain albino the guinea pigs of to determine its sensitization potential according modified Draize sensitization test.

The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration(ACC)].

In the induction phase, the total dose was administered on one occasion as 4 intradermal injections, each 2.5 times the ICC (2.5X 0.25). Fourteen days later each animal was challenged intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC (0.25 and 30 respectively). Twenty-four hours later the reactions were observed. In the absence of sensitization reactions at first challenge the induction and challenge procedures were repeated, and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included.

Based upon the second challenge, it can be concluded that 1 -phenylethanol was considered to be non-sensitizing to the skin of albino Hartley guinea pigs at 0.25% ICC and 30% ACC concentrations.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Various studies have been summarized to ascertain the extent of dermal sensitization caused by1 -Phenylethanol in living organisms. These studies include in vivo experimental results on guinea pigs and humans for the target chemical.

The skin sensitization study of 1 -Phenylethanol was carried out in 10 Inbred Hartley strain albino the guinea pigs of to determine its sensitization potential according modified Draize sensitization test.

The preliminary irritation tests were done in guinea pigs to determine concentrations suitable for sensitization testing [injection challenge concentration(ICC) and application challenge concentration(ACC)].

In the induction phase, the total dose was administered on one occasion as 4 intradermal injections, each 2.5 times the ICC (2.5X 0.25). Fourteen days later each animal was challenged intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC (0.25 and 30 respectively). Twenty-four hours later the reactions were observed. In the absence of sensitization reactions at first challenge the induction and challenge procedures were repeated, and apparent sensitization reactions confirmed 7 days later by a second challenge with controls included.

Based upon the second challenge, it can be concluded that 1 -phenylethanol was considered to be non-sensitizing to the skin of albino Hartley guinea pigs at 0.25% ICC and 30% ACC concentrations.

 This is supported by the results of an Open Epicutaneous Test (OET) performed on guinea pigs to assess the skin sensitization potential of 1 -phenyl ethanol.

The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (e.g, 100, 30,10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 8 %.

On day 1 during induction, 0.1 ml of 8% 1 -phenylethanol was applied to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of chemical to skin areas measuring 2 cm2. The reactions were read after 24, 48 and/or 72h.

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 8%.Thus, 1 -phenyl ethanol was considered to be not sensitizing on skin of guinea pigs when tested via an Open Epicutaneous Test (OET).

These studies are further supported by the results of a Human maximization test carried out with 1-phenylethanol in petrolatum on human volunteers. 8% phenylethanol in petrolatum was applied under occlusion to the same site on the forearms or backs of 25 subjects for five alternate-day 48-h periods. Patch sites were pre-treated for 24 hours with 5% aqueous sodium lauryl sulfate (SLS) under occlusion. Following a 10 days rest period, challenge patches were applied under occlusion to fresh sites for 48 hours. Challenge applications were preceded by 60 min SLS treatment. Reactions were read at patch removal and again at 72 hours.

There were no positive reactions to 8% 1-phenyl ethanol in petrolatum.

Hence, 1-phenylethanol can be considered to be not sensitizing to skin.

The above studies are also supported by the results of another Patch test performed to determine the degree of sensitization potential of 1 -phenylethanol.

179 patients suspected of cosmetic allergy were patch tested with a series of 16 fragrances an-d 9 preservatives.

For patch testing, Silver patch testes (van der Bend bv, The Netherlands) were used. Reactions were read after 48 and 72 hours, and scored according to Internationally accepted criteria.

1 -phenylethanol was tested 25% in petrolatum.

1 of 179 patients tested gave a positive reaction to 1-phenylethanol. False-positive reactions due to Excited Skin Syndrome may have occured.

Hence, 1-phenyl ethanol can be considered to be not sensitizing to skin.

Results from the available studies for 1 –Phenylethanol indicate a very strong possibility that it is indeed not sensitizing to skin. Hence, 1 –Phenylethanol can be considered to be not sensitizing to skin. 1 –Phenylethanol can be further classified under the category “Not Classified”. 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Available studies for 1-phenylethanol indicate that it is not likely to cause any dermal sensitization to humans and guinea pigs.

Hence, 1-phenylethanol can be considered to be not sensitizing to skin. It can be further classified under the category “Not Classified” as per CLP Regulation.