2-hydroxy-3-phenoxypropyl acrylate

Endpoint summary

Description of key information

The substance 2-Hydroxy-3-phenoxypropyl acrylate was tested for its sensitizing effect on the guinea pigs in the maximization test based on the method of Magnusson and Kligman (Kirsch 1990), and showed a sensitizing effect on the skin of the guinea pigs.

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

Study period:

August -September 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

The Guinea pig maximization test

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

A non-LLNA study was available before the REACH registration.

Specific details on test material used for the study:

Name used in the study report: Phenylglycidetheracrylat

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

Randomization: yes

TEST ANIMALS
- Source: Lippische Versuchstierzucht
- Females nulliparous and non-pregnant: not specified
- Weight at study initiation: 256-309 g
- Housing: Makrolon, type IV , 5/cage
- Diet (e.g. ad libitum): Kliba 341.4 mm, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: not specified
- Indication of any skin lesions: no

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Air changes (per hr): not specified ("fully air-conditionned rooms")
- Photoperiod (hrs dark / hrs light): 12/12

Route:

intradermal

Vehicle:

olive oil

Concentration / amount:

2%

Adequacy of induction:

not specified

Route:

epicutaneous, occlusive

Vehicle:

olive oil

Concentration / amount:

10%

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

olive oil

Concentration / amount:

5%

Adequacy of challenge:

highest non-irritant concentration

No.:

#2

Route:

epicutaneous, occlusive

Vehicle:

olive oil

Concentration / amount:

5%

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Main test: 10 females on control groups, 20 females on tested groups

Details on study design:

RANGE FINDING TESTS: yes.
The test substance was applied 2 times for 24 hours within a period of 96 hours in order to detect non-specific phenomena that are not caused by a sensitization reaction but could possibly be attributed to a shift in the irritation threshold.
Site of application: flank, respective on the same area
Number of test animals: 4 per test concentration
Readings: about 24 and 48 h after the beginning of application

MAIN STUDY
A. INDUCTION EXPOSURE
Intradermal induction :
- Test groups: 6 intradermal injections
A/ Front row : 2 injections each of 0.1 ml Freund's adjuvant without test substance emulsified with water in a ratio of 1:1
B/middle row: 2 injections each of 0.1 ml of the test substance formulation
C/back row: 2 injections each of 0.1 ml Freund's adjuvant/water (1:1) with the test substance
- Control groups 1 and 2: The animals were given the same injections (A, B C) but without test substance, only with the formulating agent.
- Site of application: shoulder
- Duration: not application
- Reading 24h after the beginning of application

Percutaneous induction was carried out about one week after interdermal induction
- Exposure: 2x4 cm filter paper strips were applied to the skin of the shoulder under an occlusive dressing. The animals were exposed to about 0.3 g of the test substance formulation.
- Duration: 24h
- Reading 48h after the beginning of application


B. CHALLENGE EXPOSURE
- Day(s) of challenge: First challenge, 14 days after percutaneous application, Second challenge one week later.
- Site: intact clipped flank
- Concentrations: non-irritant concentration
2x2 cm filter paper strips were applied to the skin of the flank under an occlusive dressing. The animals were exposed to about 0.15 g of the test substance formulation.
1st challenge: treatement of the test group and control group 1 with the test substance formulation. Additionally olive oil was applied as a vehicle. Control control 2 received only olive oil.
2nd challenge: treatement of the test group and control groups 1 and 2 with the test substance formulation. Additionally olive oil was applied as a vehicle.
-Duration of exposure: 24h
- Evaluation (hr after challenge): 24-48-72h after the begining of application

Challenge controls:

yes

Positive control substance(s):

no

Positive control results:

not applicable

Reading:

2nd reading

Hours after challenge:

48

Group:

other: control group 1

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

No. with + reactions:

17

Total no. in group:

20

Remarks on result:

positive indication of skin sensitisation

The number of animals with skin findings after the first challenge (20 days after intradermal induction) and after the second challenge (27 days after intradermal induction is summarized in the following table (reading at 48h after the beginning of application):

	1st challenge	1st challenge	2nd challenge	2nd challenge
	5% in olive oil	olive oil	5% in olive oil	olive oil
control group 1	0/10	0/10	6/10	0/10
control group 2	n/a	0/10	0/10	0/10
test group	17/20	0/20	18/20	0/20

 

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Under these test conditions, Phenylglycidetheracrylat has a sensitizing effect on the skin of the guinea pigs.

Executive summary:

The substance Phenylglycidetheracrylat was tested for its sensitizing effect an the skin of the guinea pig in the maximization test based an the method of Magnusson and Kligman. After intradermal induction distinct erythema and edema were observed at the injection sites of the control animals and the test animals, at which only Freund's adjuvant/aqua dest (1 : 1) was applied. Injection of test substance preparation in olive oil caused distinct erythema and edema in the test animals. The injection sites, which were applied with test substance preparation in Freund's adjuvant/aqua dest. (1 : 1> exhibited necrotic skin changes and distinct edema. The control animals, injected with olive oil (vehicle) showed distinct erythema.

After percutaneous induction necrotic skin changes (caused by the intradermal induction) were observed in addition to distinct edema in the test animals. The animals of control group one and two which were applied with olive oil (vehicle) exhibited incrustation, partially open (caused by the intradermal induction) in addition to distinct erythema and edema.

After the first challenge (48 hours after the beginning of application) with the 5% test substance preparation in olive oil, 4 out of 20 test animals showed severe erythema in addition to slight edema. 12 out of 20 test animals exhibited distinct erythema, 2 of them also showed edema. One out of 20 test animals showed slight erythema. Control group 1 didn't show any skin reactions.

The second challenge (48 hours after the beginning of application) with the 5% test substance preparation in olive oil caused distinct erythema in 6 out of 20 test animals, 3 of them showed scaling and one of these 3 animals also exhibited slight edema. In 12 out of these 20 test animals slight erythema could be observed. One out of 20 test animals showed scaling. 6/10 animals of control group 1 exhibited slight erythema. Control group 2 didn't show skin reactions.

Olive oil which was applied as a vehicle didn't cause any skin reactions in all animals after the first challenge (48 hours after the beginning of the application). After the second challenge olive oil caused scaling in 6/20 test animals. Control group 1 and 2 did not show any skin changes.

Under these test conditions and following the results described above, Phenylglycidetheracrylat has a sensitizing effect on the skin of the guinea pigs.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The substance was tested for its sensitizing effect on the skin of the guinea pig in the maximization test based a the method of Magnusson and Kligman (Kirsch 1990).

After intradermal induction distinct erythema and edema were observed at the injection sites of the control animals and the test animals, at which only Freund's adjuvant/aqua dest (1 : 1) was applied. Injection of test substance preparation in olive oil caused distinct erythema and edema in the test animals. The injection sites, which were applied with test substance preparation in Freund's adjuvant/aqua dest. (1 : 1> exhibited necrotic skin changes and distinct edema. The control animals, injected with olive oil (vehicle) showed distinct erythema.

After percutaneous induction necrotic skin changes (caused by the intradermal induction) were observed in addition to distinct edema in the test animals. The animals of control group one and two which were applied with olive oil (vehicle) exhibited incrustation, partially open (caused by the intradermal induction) in addition to distinct erythema and edema.

After the first challenge (48 hours after the beginning of application) with the 5% test substance preparation in olive oil, 4 out of 20 test animals showed severe erythema in addition to slight edema. 12 out of 20 test animals exhibited distinct erythema, 2 of them also showed edema. One out of 20 test animals showed slight erythema. Control group 1 didn't show any skin reactions.

The second challenge (48 hours after the beginning of application) with the 5% test substance preparation in olive oil caused distinct erythema in 6 out of 20 test animals, 3 of them showed scaling and one of these 3 animals also exhibited slight edema. In 12 out of these 20 test animals slight erythema could be observed. One out of 20 test animals showed scaling. 6/10 animals of control group 1 exhibited slight erythema. Control group 2 didn't show skin reactions.

Olive oil which was applied as a vehicle didn't cause any skin reactions in all animals after the first challenge (48 hours after the beginning of the application). After the second challenge olive oil caused scaling in 6/20 test animals. Control group 1 and 2 did not show any skin changes.

Under these test conditions and following the results described above, Phenylglycidetheracrylat has a sensitizing effect on the skin of the guinea pigs.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

2-Hydroxy-3-phenoxypropyl acrylate should be classified as a skin sensitizer, category 1, sub-category B, according to the CLP regulation n°1272/2008.

Justification : > 60 % of tested animals responding at > 1 % intradermal induction dose (GPMT test).