Ethyl 4-hydroxybenzoate

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating
Eye irritation (OECD 405): not 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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

other: HC:NWZ

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Hacking & Churchill Ltd., Huntingdon, UK
- Weight at study initiation: 3500 g
- Housing: Animals were housed individually
- Diet: ssniff K, ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS

- Temperature (°C): 19 - 25
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Not required, the untreated sites of the same animal served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g test substance, moistened with water

Duration of treatment / exposure:

4 h

Observation period:

7 d
reading time points: 1, 24, 48, 72 h and 7 d

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: approximately 6 cm² on the back of the animal
- Type of wrap if used: The test substance was applied to a gauze patch, held in place by elastic tape that was permeable to air.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin sites were washed with water.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Dermal application of the test substance did not result in erythema or edema in any of the animals tested at any observation time point.

Other effects:

no data on body weight and clinical observations

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

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:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

not specified

Species:

rabbit

Strain:

other: HC:NZW

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hacking & Churchill Ltd., Huntingdon, UK
- Weight at study initiation: 3500 g
- Housing: Animals were housed individually
- Diet: ssniff K, ad libitum
- Water: tap water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 40 - 60
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: Not required, the untreated eye served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 mL finely powdered test substance (corresponding to max. 0.1 mg test substance)

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 d
reading time points: 1, 24, 48, 72 h and 7 d

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with physiological saline
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: At the 24 h reading time point, 1% fluorescein solution was used to stain the cornea.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

mean value

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

mean value

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

mean value

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

On the first reading time point 1 h after washing of the eyes, conjunctivae redness was observed in all animals (score 1). After 24 h, the conjunctivae redness reversed in 2 animals and worsened in the third animal (score 2). At the 48 h reading time point, a score of 1 was recorded in that animal and the redness resolved completely within 72 h.
Swelling of the conjunctivae (score 1) was noticed in 1/3 animals at the 1 h reading time point. After 24 h, no conjunctivae swelling was observed.
No effects on iris and cornea were observed in any animal at any reading time point.

Table 1. Results of eye irritation study.

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	1	1	0	0
	24	2	0	0	0
	48	1	0	0	0
	72	0	0	0	0
	average	1.0	0.0	0.0	0.0
2	1	1	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.0	0.0	0.0	0.0
3	1	1	0	0	0
	24	0	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.0	0.0	0.0	0.0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The skin irritating properties of ethylparaben were examined in accordance with OECD 404 (Suberg, 1983). The test substance was applied on the clipped backs of three male New Zealand White rabbits and covered with a semiocclusive dressing. After 4 h, the dressing was removed and the treated skin sites were cleaned with water. Erythema and edema formation were assessed 1, 24, 48 and 72 h and 7 d after removal of the test substance using the Draize scoring system. No erythema and edema formation was observed in any animal. Under the test conditions, the test substance was not irritating to the skin.

 

In a further study, the skin irritation potential of ethylparaben was investigated using a modification of the Draize technique (Anonymous, 1980). The neat test substance or an aqueous solution of 10% (v/v) of the test substance was applied on the clipped skin of nine female albino rabbits and covered with an occlusive dressing. The dressing was removed after 24 h. Edema and erythema formation were assessed 24 and 72 h after removal of the test substance using the Draize scoring system. No erythema and edema formation was observed in any animal. Under the test conditions, the test substance was not irritating to the skin.

 

The eye irritation potential of ethylparaben was tested in a study performed by Suberg (1983) in accordance with OECD 405. The unchanged powdery test substance was instilled in one eye of each of three female New Zealand White rabbits. The other eye was not treated and served as control. At 24 h after treatment, the eyes were washed with physiological saline.

The grades of ocular reaction (conjunctivae redness, conjunctivae chemosis, cornea, iris) were assessed 1, 24, 48 and 72 h and 7 d after instillation of the test substance.

At 1 h post application, the conjunctivae of all animals showed slight redness (score 1) and chemosis was observed in one animal (score 1). The conjunctivae redness resolved in two animals and the chemosis in one animal resolved within 24 h. The conjunctivae redness in the third rabbit was fully reversible within 72 h. No corneal opacity and no effects on the iris were noted in any rabbit. Under the test conditions, the test substance was not irritating to the eyes.

 

In a further study, eye irritation of ethylparaben was investigated in a modified Draize test (Anonymous, 1980). The neat test substance or an aqueous solution of 10% (v/v) of the test substance was applied in the eyes of 6 rabbits per group. The observation period was 72 h with reading time points at 24, 48 and 72 h. An overall irritation score was estimated. In the 100% test substance group, an overall irritation score of 2 (with a max. score of 110) was estimated after 24 h. At the 48 h reading time point, the overall irritation score was 1 and after 72 h, effects had reversed completely.  

Justification for selection of skin irritation / corrosion endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
The selected study is the most adequate and reliable study based on overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data on skin irritation and eye irritation of the test substance does not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and is therefore conclusive but not sufficient for classification.