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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

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Diss Factsheets

Administrative data

Description of key information

Skin irritation/corrosion: Not irritating (Similar to OECD 404/GLP)

Serious eye damage/eye irritation (in vitro):

In vitro eye irritation test in isolated chicken eyes (ICE): Inconclusive (OECD 438/GLP)

The result of the in vitro eye irritation test was not conclusive so read-across was performed to an in vivo eye irritation study in rabbits from PEA(CAS No. 60 -12 -8).

Read-across from PEA - Serious eye damage/eye irritation (in vivo): Irritating

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:
8 -`15th November 1988 (experimental phase)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source of test material: Givaudan
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Gorseside Rabbits, Northchurch, Berkhamsted, Herfordshire, UK
- Age at study initiation: 10-12 weeks on arrival
- Weight at study initiation: 2kg
- Housing: individually in grid bottomed metal cages
- Diet: Commerically available antobiotic free rabbit diet (SQC standard rabbit pellets) ad libitum
- Water: Mains drinking water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 5-24°C. Temperature was typically greater than 14°C duing study period.
- Humidity (%): 37-68%
- Photoperiod (hrs dark / hrs light): 12 light/dark

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, 72 hrs and 7 days
Number of animals:
4
Details on study design:
TEST SITE
- Area of exposure: Dorsal skin on the trunk clipped free of hair. Left flank and immediately caudal to the last rib.
- % coverage: 6 sq.cm
- Type of wrap if used: Elastoplast elastic adhesive bandage 10cm wide

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Treated sites cleansed by gentle swabbing with cotton wool soeaked in warm water
- Time after start of exposure: 4 hrs

OBSERVATION TIME POINTS
1, 24, 48, 72 hrs and 7 days

SCORING SYSTEM:
- Method of calculation: Draize
Irritation parameter:
erythema score
Basis:
animal: 1, 3
Time point:
24 h
Score:
1
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
2
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24 h
Score:
0.5
Irritation parameter:
edema score
Basis:
animal: 1, 2, 3
Time point:
24 h
Score:
0.5
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
1.5
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
2
Remarks on result:
other: Minimal dequamation
Irritation parameter:
erythema score
Basis:
animal: 3, 4
Time point:
48 h
Score:
1
Irritation parameter:
edema score
Basis:
animal: 1, 4
Time point:
48 h
Score:
0.5
Irritation parameter:
edema score
Basis:
animal: 2, 3
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
2
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
1
Remarks on result:
other: Slight desquamation
Irritation parameter:
erythema score
Basis:
animal: 3, 4
Time point:
72 h
Score:
1
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
1
Irritation parameter:
edema score
Basis:
animal: 2, 3
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #4
Time point:
72 h
Score:
0.5
Interpretation of results:
GHS criteria not met
Conclusions:
In a primary dermal irritation study in rabbits, DMPEC was not a skin irritant.
Executive summary:

In a primary dermal irritation study (A/S/12895-12918), 4 female rabbits were dermally exposed (semi-occlusive) to 0.5mL of DMPEC for 4 hours. Animals then were observed for 7 days after dosing. Irritation was scored by the method of Draize.

The average scores calculated from the numerical values given to the irritation observed at the 24, 48 and 72 hour observations were 1.3 for erythema and 0.3 for oedema. Therefore the substance DMPEC is not a skin irritant based on the specific guidance adopted by the UNSCEGHS in June 2011.

This in vivo skin irritation/corrosion study in the rabbit is acceptable and satisfies the guideline requirement for an OECD 404 study.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Please see read-across justification.
Reason / purpose for cross-reference:
read-across source
Irritation parameter:
other: cornela necrosis
Basis:
mean
Time point:
other: Only 24 hr timepoint
Score:
8
Max. score:
10
Reversibility:
not specified
Interpretation of results:
other: Irritating
Conclusions:
Phenylethyl Alcohol is an irritant to rabbit eyes.
Executive summary:

In an eye irritation study (Carpenter et al., 1974) Phenylethyl Alcohol (undiluted) was applied to the centre of the cornea of 5 albino rabbits. The eye was examined in strong diffuse daylight 18 - 24 hours later, stained with fluorescein, and the injury scored. No vehicle was used.

Eye injury was graded according to the following 10-point scale based upon the degree of corneal necrosis that resulted. The corneal injury in rabbits was indicated as 8 out of 10. Based on the results of this study, Phenylethyl Alcohol was considered to be an eye irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion

There is one in vivo skin irritation test in rabbits available.

In a primary dermal irritation study (similar to OECD404/GLP), 4 female rabbits were dermally exposed (semi-occlusive) to 0.5mL of DMPEC for 4 hours. Animals then

were observed for 7 days after dosing. Irritation was scored by the method of Draize. The average scores calculated from the numerical values given to the irritation observed

at the 24, 48 and 72 hour observations were 1.3 for erythema and 0.3 for oedema. According to the Guidance on the Application of the CLP Criteria (v5.0, 2017), for existing

test data with more than three animals, specific guidance adopted by the UNSCEGHS in June 2011 needs to  be applied. In the case of 4 rabbits the following applies:

a. Classification as skin corrosive – Category 1 if destruction of skin tissue (visible necrosis through the epidermis and into the dermis) occurs in at least one animal after exposure up to 4 hours.

b. Classification as skin irritant – Category 2 if at least 3 out of 4 rabbits show a mean score per animal of ≥ 2.3 ≤ 4.0 for erythema/eschar or for oedema.

Therefore the substance DMPEC is not a skin irritant based on these criteria. The results from this study are acceptable to use in the human health risk assessment.

Serious eye damage/eye irritation

There is one in vitro eye irritation test in isolated chicken eyes available. There is a read-across in vivo eye irritation study in rabbits from PEA available.

In an in vitro eye irritation test in isolated chicken eyes (ICE) assay (OECD 438/GLP), isolated chicken eyes were exposed to DMPEC (99.7%) for 10 seconds. Physiological

saline (0.9% (w/v) NaCl) was used for the negative control and 5% (w/v) Benzalkonium chloride solution was used for the positive control. The control eyes and test eyes were evaluated pre-treatment and at approximately 30, 75, 120, 180 and 240 minutes after the post-treatment rinse. Corneal thickness and corneal opacity were measured at all time points. Fluorescein retention was measured on two occasions, at baseline (t=0) and approximately 30 minutes after the post-treatment rinse. No significant corneal swelling (mean ≤5%) was observed during the four-hour observation period on test item treated eyes. Slight corneal opacity change (severity 0.5 or 1) was noted on three eyes. Severe fluorescein retention change (severity 3) was observed. No other corneal effect was observed. The positive and negative controls gave the appropriate responses. The ICE classes for DMPEC were: 1xI (mean corneal swelling) 1xII (mean corneal opacity) 1xIV (mean fluorescein retention). DMPEC did not meet any of the criteria for Eye damage – Category 1. DMPEC did not meet all the criteria for Not classified (i.e. it was false that 3 endpoints were classed as I or 2 endpoints were classed as I and 1 endpoint classed as II. Based on this in vitro eye irritation in the isolated chicken eyes test with DMPEC, the test item is not classified as a severe irritant and not classified as non-irritant.

There are 2 further in vitro tests that were considered to obtain a conclusive result – OECD 437 (Bovine Corneal Opacity and Permeability (BCOP)) and OECD 492 (Reconstructed human Cornea-like Epithelium (RhCE) test). The former allows identification of chemicals with a classification of ‘Eye Damage 1’ or ‘Not Classified’ similar to OECD 438, so was not considered further. The OECD 492 allows the identification of chemicals not requiring classification and labelling for eye irritation or serious eye damage i.e. ‘Not Classified’. Based on the results of the OECD 438 study with DMPEC, it is unlikely that the substance is not irritating to the eyes (slight corneal opacity change (severity 0.5 or 1) was noted on three eyes; severe fluorescein retention change (severity 3) was observed) so performing OECD 492 was not considered. The RIFM expert panel performed an evaluation of 18 AAA fragrance ingredients for eye irritation (DMPEC was one the substances in this group though there are no eye irritation studies available). Together the studies showed that the undiluted materials cause moderate to severe eye irritation. Based on the in vitro results and RIFM opinion, it was concluded that DMPEC is likely irritating to the eye (‘Eye irritation – Category 2). Currently there is no in vitro eye irritation test that allows identification of chemicals with a classification of ‘Eye irritation – Category 2’. To avoid animal testing, read-across was performed to an in vivo eye irritation study in rabbits from PEA.

In an eye irritation study (no guideline), PEA (undiluted) was applied to the centre of the cornea of 5 albino rabbits. The eye was examined in strong diffuse daylight 18 - 24 hours later, stained with fluorescein, and the injury scored. No vehicle was used. Eye injury was graded according to the following 10-point scale based upon the degree of corneal necrosis that resulted. The corneal injury in rabbits was indicated as 8 out of 10. Based on the results of this study, PEA was considered to be an eye irritant. DMPEC was predicted to be an eye irritant (Eye irritation – Category 2) based on the weight of evidence.

The results from this study are acceptable to use in the human health risk assessment.

 
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    
    

In an eye irritation study (Carpenter et al., 1974) Phenylethyl Alcohol (undiluted) was applied to the centre of the cornea of 5 albino rabbits. The eye was examined in strong diffuse daylight 18 - 24 hours later, stained with fluorescein, and the injury scored. No vehicle was used.

Eye injury was graded according to the following 10-point scale based upon the degree of corneal necrosis that resulted. The corneal injury in rabbits was indicated as 8 out of 10. Based on the results of this study, Phenylethyl Alcohol was considered to be an eye irritant.

Justification for classification or non-classification

Based on the available information in the dossier, the substance DMPEC (CAS No. 103-05-9) is classified as Eye irritation Category 2 for serious eye damage/eye irritation based on the results of the read-across study from Phenethyl alcohol (CAS No. 60 -12 -8) and does not need to classified for skin irritation/corrosion when considering the criteria outlined in Annex I of 1272/2008/EC.