Reaction product of p-nonylphenol, formaldehyde and diethanolamine, propoxylated

Eye irritation

Administrative data

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other: GLP-compliant guideline study available as unpublished report, no restrictions, fully adequate for assessment.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Remarks:

Toxi-Coop Zrt., Pálya u. 2, 2120 Dunakeszi, Hungary

Test material

Test material information

Constituent 1

Reference substance name:

Propoxylated reaction products of phenol, 4-nonyl-, branched and formaldehyde and 2,2'- iminodiethanol

EC Number:

701-426-6

Molecular formula:

Not applicable (UVCB substance)

IUPAC Name:

Propoxylated reaction products of phenol, 4-nonyl-, branched and formaldehyde and 2,2'- iminodiethanol

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Petol PM 410-4N
- Physical state: yellow-brown (apparently yellow), viscous, clear liquid
- Storage condition of test material: Store in tightly closed container, in a dry and well ventilated area, between 20-30°C.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: S & K LAP Kft. 2173 Kartal, Császár út 135, Hungary
- Age at study initiation: adult rabbits
- Weight at study initiation: 3001 - 3130 g
- Housing: Individually in metal cages.
- Diet: Rabbit fattening mixed diet produced by YAQ-TÁP Kft., Nyíregyháza (Tokaji út 22), Hungary, ad libitum.
- Water: Tap water from watering bottles ad libitum.
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3
- Humidity: 30-70
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

single exposure, eyes were not washed out after exposure

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 (males)

Details on study design:

TESTING PROCEDURE
Three male animals in acceptable health condition were selected for the test. Care was taken to select only those animals that had a normal eye condition, any with ocular lesions were rejected. In the first step an initial test was performed using one animal. The test item was poured into the conjunctival sac of the left eye. The eyelids were held closed gently for several seconds to prevent the loss of the test item. The contralateral eye served as control. Immediately after the administration of the test item, an assessment of the initial pain reaction was made. After consideration of the ocular responses produced in the first animal, two additional animals were treated 1 hour after the treatment of the first animal. Before administration the treated eyes of the animals were not anaesthetised, because the score of initial pain reaction was 2 in the first animal. The eyes of the test animals were not washed out after the application of test item.

CLINICAL OBSERVATIONS
The eyes were examined at 1, 24, 48 and 72 hours then 1 week after the application. The duration of the observation period was sufficient for the statement of reversibility or irreversibility of changes. At the end of the observation period the animals were humanely sacrificed. The body weights were recorded at the beginning and at the end of the experiment.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

mean

Remarks:

all test animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

all test animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 1 week

Results 4

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 1 week

Results 5

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 1 week

Results 6

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 1 week

Results 7

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 1 week

Results 8

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 1 week

Results 9

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #1

Remarks:

mean

Time point:

24/48/72 h

Score:

2.66

Max. score:

3

Reversibility:

fully reversible within: 1 week

Results 10

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #2

Remarks:

mean

Time point:

24/48/72 h

Score:

2.66

Max. score:

3

Reversibility:

fully reversible within: 1 week

Results 11

Irritation parameter:

conjunctivae score

Remarks:

discharge

Basis:

animal #3

Remarks:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

fully reversible within: 1 week

Irritant / corrosive response data:

- One hour after the treatment diffuse, crimson coloured conjunctivae with not easily discernible individual vessels (score 2) occurred in animal No.: 01347 and some hyperemic blood vessels (score 1) were observed in two animals (No.: 01351, 01301). The obvious swelling with partial eversion of lids (score 2) were recorded in two animals (No.: 01347, 01351). The conjunctival swelling with lids about half closed (score 3) was detected in animal No.: 01301. Discharge moistened lids and hairs on considerable area around the treated eye (score 3) was found in all animals.
- 24 hours after the treatment diffuse, crimson coloured conjunctivae with not easily discernible individual vessels (score 2) occurred in two animals (No.: 01347, 01301) and some hyperemic blood vessels (score 1) were observed in animal No.: 01351. The obvious swelling with partial eversion of lids (score 2) were recorded in animal No.: 01351. The conjunctival swelling with lids about half closed (score 3) was detected in two animals (No.: 01347, 01301). Discharge moistened lids and hairs on considerable area around the treated eye (score 3) was found in all animals.
- 48 hours after the treatment diffuse, crimson coloured conjunctivae with not easily discernible individual vessels (score 2) occurred in two animals (No.: 01347, 01301) and some hyperemic blood vessels (score 1) were observed in animal No.: 01351. The obvious swelling with partial eversion of lids (score 2) were recorded in two animals (No.: 01347, 01351). The conjunctival swelling with lids about half closed (score 3) was detected in animal No.: 01301. Discharge moistened lids and hairs on considerable area around the treated eye (score 3) was found in all animals.
- 72 hours after the treatment diffuse, crimson coloured conjunctivae with not easily discernible individual vessels (score 2) occurred in animal No.: 01301 and some hyperemic blood vessels (score 1) were observed in two animals (No.: 01347, 01351). The obvious swelling with partial eversion of lids (score 2) were recorded in two animals (No.: 01347, 01351). The conjunctival swelling with lids about half closed (score 3) was detected in animal No.: 01301. The discharge moistened lids and hairs on considerable area around the treated eye (score 3) were recorded in animal No.: 01301 and the discharge with moistening of the lids and hairs just adjacent to lids (score 2) was observed in two animals (No.: 1347, 01351).
- 1 week after the treatment all animals became free of symptoms.

Other effects:

General state and the behaviour of animals were normal throughout the study period. There were no notable body weight changes during the contact and observation period.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance is, in a GLP compliant OECD 405 guideline study, considered to be irritating to the eye.

Executive summary:

In a GLP compliant acute eye irritation study performed according to OECD guideline 405, the irritating potential of Petol PM 410-4N was investigated. Three male new Zealand White rabbits were treated once with 0.1 mL of pure test substance in the conjunctival sac of the left eye, the untreated right eye served as control. The treated eye was not washed out after treatment. Rabbits were scored for irritating effects after 1, 24, 48, 72 hours and one week. General state and behaviour of animals were normal throughout the study period. There were no notable body weight changes during the contact and observation period. One hour after the application, slight to moderate redness, moderate to severe chemosis and severe discharge occurred. There was no important change compared with the 1 hour observation at 24, 48 and 72 hours after the treatment. One week after treatment the study was terminated, because all animals were free of symptoms of irritation. Based on the results of the study, the test substance is considered to be irritating to the eye.