Phenol, paraalkylation products with C10-15 branched olefins ( C12 rich) derived from propene oligomerization, calcium salts, sulfurized, including distillates (petroleum), hydrotreated, solvent-refined, solvent-dewaxed, or catalyc dewaxed, light or heavy paraffinic C15-C50

Endpoint summary

Description of key information

Skin: The primary dermal irritation potential of the test material was evaluated in rabbits under 4-hour semioccluded conditions (Glaza, 1997). The test material produced very slight to well-defined erythema and slight to moderate edema reactions. No other dermal irritation was observed. All irritation cleared by the Day 7 observation. The average of the 24-, 48-, and 72-hour scores are 1.2 for erythema and 1.3 for edema.

Eye: The primary eye irritation potential of the test material was evaluated when 0.1 mL was instilled into one eye of each of nine rabbits (six with treated eyes unwashed and three with treated eyes washed for 1 minute starting 30 seconds after instillation) (Glaza, 1997). The test material produced a corneal opacity in one animal and conjunctival irritation in all unwashed eyes which cleared in all animals by 96 hours after treatment. Positive irritation reactions were observed in five of the six animals with unwashed eyes which cleared in all animals by the 48-hour observation. In treated eyes receiving a washout, the test material produced only conjunctival irritation which cleared in all animals by 72 hours after treatment. Positive irritation reactions were observed in two of the three animals with washed eyes which cleared in all animals by the 48-hour observation. Rinsing the eyes after treatment did not have a substantial effect on the severity and persistence of ocular irritation.
The mean 24 -78 hour scores were: corneal opacity (0), iris lesions (0), conjuctival redness (0.9), and chemosis (0.1). Therefore, classification for eye irritation is not warrnated.

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

Study period:

"In Life" dates 12th to 19th September 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study following GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

other: Hra:(NZW)SPF strain

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HRP, Inc., Kalamazoo, Michigan on September 4, 1996.
- Age at study initiation: approximately 13 weeks of age
- Weight at study initiation: weighing from 2,098 to 2,427 g
- Housing: the animals were individually housed in suspended stainless steel cages.
- Diet/water (e.g. ad libitum): The animals were provided access to water ad libitum and a measured amount of Laboratory Rabbit Diet HF #5326, PMI Feeds, Inc. The feed is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Samples of the water are periodically analyzed. There were no known contaminants in the feed or water at levels that could be expected to interfere with or affect the results of the study.
- Acclimation period: After receipt, the animals were acclimated for a period of at least 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19° to 23 °C
- Humidity (%): 50% +20%
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark lighting cycle

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Concentration (if solution): The undiluted test material was applied to the intact skin site on each animal's back (approximate exposure area of 6.25 cm2) in the amount of 0.5 mL.

Duration of treatment / exposure:

four hours

Observation period:

4, 24, 48, 72, 96 hours and 7 days.

Number of animals:

Three per sex per dose (male and female)

Details on study design:

TEST SITE
- Area of exposure: 6.25 cm2
- Type of wrap if used: The area of application was covered with a 4-ply 2.5-cm x 2.5-cm gauze patch secured with two strips of Micropore surgical tape. The trunk of the animal was then loosely overwrapped with a sheet of perforated plastic film that was secured on both ends with strips of Elastoplast® tape to provide a semiocclusive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the 4-hour exposure period, the patches were removed and any remaining test material was removed from the test sites using mineral oil followed by liquid Ivory® soap mixed with warm tap water. The test sites were then rinsed with clean tap water and dried with disposable paper towels. The test material was removed from the test sites as thoroughly as possible without irritating the skin. The area of control skin was treated in the same manner.

SCORING SYSTEM:
Thirty minutes after removal of the test material, the degree of erythema and edema at each test site was read according to the Draize technique (recorded as the 4-hour score). Subsequent examinations were made at 24, 48, 72, and 96 hours and Day 7. An area of untreated skin on each animal was used for comparison.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Score:

2.8

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: The primary dermal irritation index (PDII) is the sum of the individual index scores, divided by the number of animals, and rounded to the nearest tenth.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 hours

Score:

1.5

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48 hours

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 hours

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 hours

Score:

1.8

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48 hours

Score:

1.2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 hours

Score:

0.8

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

Application of the test material to the skin of rabbits under 4-hour semioccluded conditions resulted in very slight to well-defined erythema and slight to moderate edema reactions. No other dermal irritation was observed. All irritation cleared by the Day 7 observation.

The average of the individual animal index scores is 2.8. The average of the 24-, 48-, and 72-hour scores are 1.2 for erythema and 1.3 for edema.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material produced very slight to well-defined erythema and slight to moderate edema reactions. No other dermal irritation was observed. All irritation cleared by the Day 7 observation.

Executive summary:

In an acute dermal irritation study in the New Zealand White Rabbit conducted to OECD guideline 404 in accordance with GLP, the primary dermal irritation potential of the test material was evaluated in rabbits under 4-hour semi-occluded conditions. The test material produced very slight to well-defined erythema and slight to moderate edema reactions. No other dermal irritation was observed. All irritation cleared by the Day 7 observation. The average of the individual index scores (the total of the erythema and edema scores at 4, 24, 48, and 72 hours divided by 4) is 2.8. The average of the 24-, 48-, and 72-hour scores are 1.2 for erythema and 1.3 for edema.

The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 1.2 and so will not be classified as irritating.

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

Study period:

16th to 29th September 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study following GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Adult albino rabbits of the Hra:(NZW)SPF strain were procured from HRP, Inc., Kalamazoo, Michigan on September 4, 1996.
- Age at study initiation: approximately 14 to 18 weeks of age
- Weight at study initiation: weighing from 2,209 to 2,514 g
- Housing: the animals were individually housed in suspended stainless steel cages
- Diet/water (e.g. ad libitum): The animals were provided access to water ad libitum and a measured amount of Laboratory Rabbit Diet HF #5326, PMI Feeds, Inc. The feed is routinely analyzed by the manufacturer for nutritional components and environmental contaminants. Samples of the water are periodically analyzed. There were no known contaminants in the feed or water at levels that could be expected to interfere with or affect the results of the study.
- Acclimation period: After receipt, the animals were acclimated for a period of at least 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19° to 23°C
- Humidity (%): 50% ±20%
- Photoperiod (hrs dark / hrs light): 12-hour light/12¬hour dark lighting cycle

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

Dose level: 0.1 ml/one eye/animal
(Group 1, eyes unwashed post dosing N=6, Group 2, eyes washed post dosing N=3),

Duration of treatment / exposure:

The test material was not washed from the eyes of the animals in Group 1. The treated eyes of the rabbits in Group 2 were flushed with lukewarm tap water for 1 minute starting 30 seconds after test material instillation.

Observation period (in vivo):

Treated eyes were examined at 1, 24, 48 and 72 hours after treatment. An additional observation was made at 96 hours after treatment for the
Group 1 animals (unwashed).

Number of animals or in vitro replicates:

5 males; 4 females (six were used for group 1 and 3 for group 2)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The eyes of the rabbits in Group 1 remained unflushed immediately after treatment while the treated eyes of the rabbits in Group 2 were flushed with lukewarm tap water for 1 minute starting 30 seconds after test material instillation.

SCORING SYSTEM: Irritation was graded and scored according to the Draize technique using a penlight as the source of illumination. A sodium fluorescein examination was used to aid in revealing possible corneal injury at the observation conducted at 24 hours.

TOOL USED TO ASSESS SCORE: sodium fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 & 72 hours

Score:

0

Reversibility:

other: no effects seen

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 & 72 hours

Score:

0

Reversibility:

other: no effects seen

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 hours

Score:

1.8

Max. score:

2

Reversibility:

fully reversible within: 96 hours

Remarks on result:

other: Redness

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 48 hours

Score:

0.8

Max. score:

1

Reversibility:

fully reversible within: 96 hours

Remarks on result:

other: Redness

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 72 hours

Score:

0.2

Max. score:

1

Reversibility:

fully reversible within: 96 hours

Remarks on result:

other: Redness

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 hours

Score:

0.3

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

The test material when evaluated for its primary eye irritation potential in rabbits, produced a corneal opacity in one animal and conjunctival irritation in all treated eyes that were unwashed after treatment.

Other effects:

Two animals exhibited hair loss around the treated eye

The potential eye-irritancy of the substance was investigated in a study conduted in line with OECD guideline 405 under conditions of GLP. The test material when evaluated for its primary eye irritation potential in rabbits, produced a corneal opacity in one animal and conjunctival irritation in all treated eyes that were unwashed after treatment. All treated eyes in this group returned to a normal appearance by 96 hours after treatment with the exception that two animals exhibited hair loss around the treated eye. Positive irritation reactions were observed in five of the six animals with unwashed eyes which cleared in all animals by the 48-hour observation. In treated eyes receiving a washout after test material instillation, the test material produced only conjunctival irritation. All treated eyes in this group returned to a normal appearance by 72 hours after treatment. Positive irritation reactions were observed in two of the three animals with washed eyes which cleared in all animals by the 48-hour observation. Rinsing the eyes after treatment did not have a substantial effect on the severity and persistence of ocular irritation.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material when evaluated for its primary eye irritation potential in rabbits, produced a corneal opacity in one animal and conjunctival irritation in all treated eyes that were unwashed after treatment. All treated eyes in this group returned to a normal appearance by 96 hours after treatment with the exception that two animals exhibited hair loss around the treated eye. Positive irritation reactions were observed in five of the six animals with unwashed eyes which cleared in all animals by the 48-hour observation.

Executive summary:

The primary eye irritation potential of the test material was evaluated when 0.1 mL was instilled into one eye of each of nine rabbits (six with treated eyes unwashed and three with treated eyes washed for 1 minute starting 30 seconds after instillation). The test material produced a corneal opacity in one animal and conjunctival irritation in all unwashed eyes which cleared in all animals by 96 hours after treatment. Positive irritation reactions were observed in five of the six animals with unwashed eyes which cleared in all animals by the 48-hour observation. In treated eyes receiving a washout, the test material produced only conjunctival irritation which cleared in all animals by 72 hours after treatment. Positive irritation reactions were observed in two of the three animals with washed eyes which cleared in all animals by the 48-hour observation. Rinsing the eyes after treatment did not have a substantial effect on the severity and persistence of ocular irritation.

The mean value of the scores for cornea opacity, iris lesions, redness & oedema of the conjuctivae, for 24, 48 and 72 hours was calculated and was considered to be non-irritating according to the classification criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The Glaza (1997) studies were chosen as the key studies for both skin and eye irritation as they were the most recent, guideline, and GLP studies. Multiple studies have been conducted with the registered material but many did not have sufficient information to fully evaluate the study. In addition, many of the skin irritation studies were not valid because the test material was either not removed from the skin or a solvent was used that may not have completely removed the test substance and/or irritated the skin. The registered substance is a viscous liquid and a mineral oil wipe step is necessary to completely remove the test material.

Justification for classification or non-classification

Skin:

The skin irritation observed in the key study was less than the classification criteria, therefore classification for skin irritation was not considered to be necessary.

Eye:

The eye irritation observed in the key study was less than the classification critieria, therefore classification for eye irritation was not considered to be necessary.