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

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

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

Adequacy of study:

key study

Study period:

1991-08-05 until 1991-10-30

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.5. Termination of initial test for humane reasons (severe ocular lesions) after 1 hour is unlikely to have compromised the result. The fact that the study is used for read-across purposes triggers reliability rating 2.

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.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

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:

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

EC Number:

407-960-3

EC Name:

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

IUPAC Name:

407-960-3

Constituent 3

Reference substance name:

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

IUPAC Name:

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

Constituent 4

Reference substance name:

94050-90-5

Cas Number:

94050-90-5

IUPAC Name:

94050-90-5

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

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
- Purity test date: 1991-06-17
- Expiration date of the lot/batch: 1992-01-15
- Storage condition of test material: room temperature

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Froxfield Farms (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: 12 weeks
- Weight at study initiation: 2840 g
- 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: 1991-08-05 To: 1991-08-05 (terminated on same day)

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approx. 77 mg, corresponding to 0.1 mL volume
- Concentration: 100%, finely ground powder
- placed into the lower everted lid of one eye, lids held together for 1 second
- Untreated eye serves as control

Duration of treatment / exposure:

1 hour, until dense corneal opacity (grade 4) was detected, and the experiment was terminated for humane reasons

Observation period (in vivo):

1 hour, until dense corneal opacity (grade 4) was detected, and the experiment was terminated for humane reasons (in accordance with EU Method B.5, sequential testing strategy, initial test)

Number of animals or in vitro replicates:

1 female

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM:
- According to EU Method B.5, Table 1: Grading of Ocular Lesions

TOOL USED TO ASSESS SCORE: handheld light

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1 hour

Score:

4

Max. score:

4

Reversibility:

other: no reversibility to be expected

Remarks on result:

other: dense corneal opacity covering the entire corneal surface

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 hour

Max. score:

2

Reversibility:

other: experiment terminated for humane reasons

Remarks on result:

other: Assessment of iridial inflammation impossible due to corneal opacity

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1 hour

Score:

1

Max. score:

3

Reversibility:

other: experiment terminated for humane reasons

Remarks on result:

other: whitening (blanching) of eyelids

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 1 hour

Score:

2

Max. score:

4

Reversibility:

other: experiment terminated for humane reasons

Other effects:

Slight ocular discharge
No signs of toxicity or ill health observed during the (very short, 1 h) exposure period.

Any other information on results incl. tables

Severe ocular lesions (dense corneal opacity) 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 aqueous solution; the study was terminated for humane reasons after 1 hour. From the data, it cannot be decided whether this severe ocular response reflects effects of low pH or structural properties common to the source and the target molecule, e.g. the phenolic group.

It cannot be excluded by read-across that propanoic acid, 2-(4-hydroxyphenoxy)-, sodium salt (2R) (CAS 133647-88-8) may be irritant with the risk of serious damage to the eye.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

It cannot be excluded by read-across that sodium (2R)-2-(4-hydroxyphenoxy)propanoate may cause serious eye damage.