4-chlorophenol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April to June 1980

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

Test procedure in accordance with generally accepted scientific standards and described in sufficient detail. Applicant assessment indicates that any deviation from current guidelines would not have affected the study outcome.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

4-chlorophenol

EC Number:

203-402-6

EC Name:

4-chlorophenol

Cas Number:

106-48-9

Molecular formula:

C6H5ClO

IUPAC Name:

4-chlorophenol

Test material form:

solid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Recognised supplier
- Age at study initiation: unspecified
- Weight at study initiation: 3 - 4 kg
- Housing: individually housed in rabbit cages.
- Diet: Standard mixed rabbit food, ad libitum.
- Water: Water, ad libitum
- Acclimation period: Time not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Unspecified; ambient laboratory temperature.
- Humidity (%): Unspecified; ambient laboratory humidity.
- Air changes (per hr): Unspecified.
- Photoperiod (hrs dark / hrs light): Unspecified.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 50 mg (per animal)
- Concentration (if solution): undiluted

Duration of treatment / exposure:

A quantity of 50 mg of the undiluted test material, was placed into the conjunctival sac of one eye. The other eye remained untreated.

Observation period (in vivo):

Ocular assessment was conducted daily over the following 7 days.

Number of animals or in vitro replicates:

2 (1 male and 1 female).

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Unspecified; applicant assessment: assumed none.

SCORING SYSTEM:
The ocular reaction was described in the report in prose at daily intervals after instillation, for the following 7 days. Applicant assessment indicates that the prose description contains sufficient detail for the results to be interpreted according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992. This scoring system is consistent with Draize scoring system. When present, corrosion and/or staining of conjunctivae, sclerae and cornea by the test item were recorded and reported.

TOOL USED TO ASSESS SCORE: Eye examinations were made manually, equipment details are unspecified. Applicant assessment indicates that no special equipment would be necessary to determine the outcome of the study (from the description, the results would have been clearly visible to the naked eye).

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 0 - 7d

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: mean; n=2. Cornea totally corroded.

Results 2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 0 - 6d

Score:

3

Max. score:

3

Reversibility:

not specified

Remarks on result:

other: mean; n=2. Strong reddening.

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

7 d

Score:

2

Max. score:

3

Reversibility:

not specified

Remarks on result:

other: mean; n=2. Moderate reddening.

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 0 - 6d

Score:

4

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: mean; n=2. Strong reddening.

Results 5

Irritation parameter:

chemosis score

Basis:

mean

Time point:

7 d

Score:

3

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: mean; n=2. Moderate reddening.

Results 6

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 0 - 7d

Max. score:

4

Remarks on result:

not measured/tested

Remarks:

Iris observations not reported; Applicant assessment indicates this would have been deemed either not possible or unnecessary due to severe corneal corrosion.

Results 7

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Indication of corrosion

Remarks:

Cornea totally corroded

Results 8

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Indication of corrosion

Remarks:

Cornea totally corroded

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Remarks:

Severe reddening

Results 10

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Remarks:

Severe reddening

Results 11

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Remarks:

Strong reddening

Results 12

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not specified

Remarks on result:

positive indication of irritation

Remarks:

Strong reddening

Results 13

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

Iris observations not reported; Applicant assessment indicates this would have been deemed either not possible or unnecessary due to severe corneal corrosion, thereby not having any effect on the classification of the substance.

Results 14

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Max. score:

4

Reversibility:

not specified

Remarks on result:

not measured/tested

Remarks:

Iris observations not reported; Applicant assessment indicates this would have been deemed either not possible or unnecessary due to severe corneal corrosion, thereby not having any effect on the classification of the substance.

Irritant / corrosive response data:

"Total corrosion" of the cornea was noted at all observations. "Strong reddening" of the conjunctivae of treated eyes was observed immediately and for the following 6 days after treatment, although partially resolved to "moderate reddening" by the final observation. "Strong" chemosis of the conjunctivae was observed in both animals immediately after treatment, for the following 6 days, which reduced to "moderate" chemosis by the final observation. An iris score was not recorded in the study report. Applicant assessment indicates that this would not change the classification of the substance.

Other effects:

- Lesions and clinical observations: Total corrosion of the cornea; strong irritation of the conjunctiva with only partial reversal by the end of the study.
- Ophthalmoscopic findings: None reported.
- Histopathological findings: Not applicable.
- Effects of rinsing or washing: Not applicable.
- Other observations: Not applicable.

Any other information on results incl. tables

Table 1. Individual scores and mean scores for the 7 day observation period

Organism number	1		2
Time After Treatment	0 - 6 days	7 days	0 - 6 days	7 days
CORNEA
Degree of Opacity	4	4	4	4
Mean (24 – 72 h)
Area of Cornea Involved	4	4	4	4
IRIS	Not assessed	Not assessed	Not assessed	Not assessed
Mean (24 – 72 h)
CONJUNCTIVAE
Redness	3	2	3	2
Mean (24 – 72 h)
Chemosis	4	3	4	3
Mean (24 – 72 h)

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this study the test item is strongly irritating and corrosive to the eye.

Executive summary:

The study was performed historically to a guideline similar to OECD TG 405 and EU Method B.5 to assess the irritancy potential of the test item to the eye following a single application in the New Zealand White rabbit. Applicant assessment indicates that any deviation from the current guidelines would not have a significant effect on the study outcome. A volume of 50 mg of the test material was placed into the conjunctival sac of one eye of two rabbits. The other eye remained untreated. Assessment of ocular damage/irritation was made daily for 7 days following treatment. A single application of the test item to the non-irrigated eye of two rabbits produced immediate total corrosion of the cornea. "Strong" redness of the conjunctivae was observed in all treated eyes immediately after treatment, which persisted for 6 days. This reduced to "moderate" redness by the final (day 7) observation. "Strong" chemosis was observed in both treated eyes immediately after treatment, persisting for the following 6 days. This reduced to "moderate" chemosis by the final (day 7) observation. The study authors note "Aufgrund der stark ausgepraegten Reiz- und Aetzwirkung ist jedoch jeder Haut- und Schleimhautkontakt (Auge) mit dem Pruefmuster unbedingth zu vermeiden.", i.e. "Due to the pronounced irritant and caustic effect, any skin and mucous-membrane contact (eye) with the test item must be avoided." Furthermore, the authors note, "...jeglicher Haut- und Schleimhautkontakt (Auge) ist unbedingt zu vermeiden.", i.e. "any contact with skin or mucous membranes (eye) should be avoided at all costs". Under the conditions of this study, the test item is therefore considered to be strongly irritating and corrosive to the eye.