Propanoic acid, 2-(4-hydroxyphenoxy)-, potassium salt (1:1), (2R)-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

1991-07-30 to 1991-08-02

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP study on structural analogue (free acid) according to guideline: EEC Directive 84/449/EEC Method B.4.; no reference to OECD guideline. The fact that the study is used for read-across purposes triggers reliability rating 2. No signs of skin irritation were observed with the acid (pH 1.8) in any animal at any time, therefore the K+ salt with its next-to-neutral pH is unlikely to be a skin irritant. The additional amount of potassium applied to the skin is not expected to be taken up and elicit systemic adverse effects.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Observation terminated after 72 hours (no observable effects)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

(R)-2-(4-Hydroxyphenoxy)propanoic acid

IUPAC Name:

(R)-2-(4-Hydroxyphenoxy)propanoic acid

Constituent 2

Reference substance name:

Propanoic acid, 2-(4-hydroxyphenoxy)-, (2R)-

IUPAC Name:

Propanoic acid, 2-(4-hydroxyphenoxy)-, (2R)-

Constituent 3

Reference substance name:

94050-90-5

Cas Number:

94050-90-5

IUPAC Name:

94050-90-5

Constituent 4

Reference substance name:

(R)-2-(4-hydroxyphenoxy)propanoic acid

EC Number:

407-960-3

EC Name:

(R)-2-(4-hydroxyphenoxy)propanoic acid

IUPAC Name:

407-960-3

Details on test material:

- Name of test material (as cited in study report): D-HPPA
- Substance type: pure test substance
- Physical state: off-white / gray powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 10 - 12 weeks
- Weight at study initiation: 2.3 - 2.7 kg
- Housing: individually in metal cages with perforated floors
- Diet: SDS Stanrab (P) Rabbit Diet ad libitum
- Water: ad libitum
- Acclimation period: yes, duration not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 1991-07-30 To: 1991-08-02

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Remarks:

distilled

Controls:

not required

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours
washing with water after removal of the semiocclusive dressing and gauze

Observation period:

30 min after removal of dressings, 24, 48, and 72 hours

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm square, approximately 6cm2
- Type of wrap if used: gauze pad (moistened with 0.5 mL distilled water), Elastoplast elastic adhesive dressing, semiocclusive
- Animals not restrained

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water, to remove any residual test substance
- Time after start of exposure: 4 hours

SCORING SYSTEM:
-According to EU Method B.4, Table 1: Grading of Skin Reactions

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 3

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 6

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No dermal response to treatment in any animal at any time point

Other effects:

No signs of toxicity or ill health throughout the observation period

Any other information on results incl. tables

No signs of skin irritation were observed with the source substance, the free acid (R)-2-(4-hydroxyphenoxy)-propanoic acid (CAS 94050-90-5), which has pH 1.8 in concentrated aqueous solution, in any animal at any time.

The skin irritation potential of the target substance propanoic acid, 2-(4-hydroxyphenoxy)-, potassium salt (2R) (CAS 1184648-08-5) is determined by read-across from the test with the free acid. The analogue approach is based on the facts that source and target contain the identical molecular structure and the same functional groups (except the K+ counterion), and that the K+ salt is expected to have a next-to-neutral pH, below 8.5 - 9. The additional amount of potassium applied to the skin is not expected to permeate the skin due to its ionic nature, therefore it is not taken up and will not elicit systemic adverse effects.

As a conclusion, propanoic acid, 2-(4-hydroxyphenoxy)-, potassium salt (2R) is not expected to be a skin irritant.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Potassium (R)-2-(4-hydroxy-phenoxy)-propionate is not expected to be a skin irritant derived from read-across.