Naphthalenesulfonic acid, di-C9-rich C8-10-branched alkyl derivs., calcium salts

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 study with no significant deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

NA-SUL 729

IUPAC Name:

NA-SUL 729

Details on test material:

50% calcium dinonylnaphthalene sulfonate and 50% light mineral oil.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three male and three female (nulliparous and non-pregnant) New Zealand White rabbits were obtained from Hazleton Research Products, Inc.,
Denver, PA. and held in quarantine for 12 days. During quarantine the animals appearance and behavior were recorded daily.
The animals were individually housed in suspended cages with wire mesh bottoms. The absorbent paper under the cages was changed daily. The animals were fed a restricted diet (125 glday) of Purina High Fiber Lab Chow #5326 and received well water gd libitum. No contaminant was
expected to be present in the feed or water at a level sufficient to interfere with the study. The animals were transferred to another room on day 2 of the study. The room temperature of the first room was maintained at 66-69° F with a relative humidity of 34-82%. The room temperature of the
second room was maintained at 66-70° F with a relative humidity of 26-71%.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

Single treatment with 10 days of observation

Observation period (in vivo):

Both eyes were grossly examined and the test eye scored by the Draize method at 1,24,48, and 72 hours and at 7 and 10 days after instillation of the test material.

Number of animals or in vitro replicates:

3 male and 3 female

Details on study design:

The eyes were prescreened for ocular defects and/or irritation on the day prior to testing. The left eye was designated as the test eye while the
right eye was designated as the control. A 0.1 ml aliquot was drawn into a 1 cc syringe and instilled into the left conjunctival sac by gently pulling
the lower lid away from the eyeball to form a cup. The eyelids were gently held together for approximately one second after instillation.
Both eyes were grossly examined and the test eye scored by the Draize method (See Appendix 1) at 1,24,48, and 72 hours and at 7 and 10 days after instillation of the test material. All eyes were also examined for the presence of corneal ulcerations at 24 hours using 2% sodium fluorescein.
Animals with ulcerations were reexamined with 2% fluorescein sodium during subsequent observations until the ulcerations were no longer
apparent. A plastic Elizabethan style collar was placed on each animal to prevent mechanical irritation of the eye. Mortality checks were performed daily. Clinical observations were performed daily except on the weekend. The animals were euthanized by overexposure to carbon dioxide on day 10 of the study.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.8

Max. score:

1.5

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0.1

Results 3

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

2.8

Reversibility:

fully reversible within: 10 days

Results 4

Irritation parameter:

conjunctivae score

Remarks:

swelling

Basis:

mean

Time point:

24/48/72 h

Score:

2.5

Max. score:

3.3

Reversibility:

fully reversible within: 10 days

Irritant / corrosive response data:

Slight corneal opacities and iridial irritation were noted in 3/6 animals and moderate to severe conjunctival irritation in all animals at 1 hour. The number of animals with corneal opacities increased to 6/6 at 24 hours. The density of several opacities increased and corneal ulcerations
were present in all animals. The number of corneal opacities decreased to 3/6 at 48 hours and 1/6 at 72 hours. All opacities were clear by day 7. The number of corneal ulcerations decreased to 3/6 at 48 hours and 0/6 at 72 hours. Moderate to severe conjunctival irritation was still present
at 24 hours and diminished slowly over the remainder of the study.

Other effects:

Soft stool was noted in all animals on day 1 and in 2/6 animals on day 2. Decreased food consumption and decreased fecal output were noted in 2/6 animals on days 1 and 6, respectively. No other clinical observations were noted.

II.

Any other information on results incl. tables

Observation	1-Hr	24-Hrs	48-Hr	72-Hr	7-Days	10-Days	Mean Days1-3
Corneal Opacity	0.3	1.5	0.7	0.2	0.0	0.0	0.8
Iritis	0.5	0.0	0.0	0.0	0.0	0.0	0.0
Conjunctival Redness	2.7	2.8	2.0	1.2	0.7	0.0	2.0
Conjunctival Swelling	2.3	3.3	2.2	2.0	0.5	0.0	2.5

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

NA-SUL 729 is also an eye irritant according to EC guidelines because the combined mean conjunctival swelling score (24-, 48-, 72-hours) is
greater than 2.0.

Executive summary:

The acute ocular irritation of NA-SUL 729 was evaluated in three male and three female New Zealand White rabbits. A single 0.1 ml aliquot of the test material was instilled into the left conjunctival sac of each animal. The eye was gently held shut for approximately one second. A plastic Elizabethan collar was placed on each animal after dosing to prevent access to the test site. Both eyes were examined and the test eye scored according to the Draize method at 1, 24, 48, and 72 hours and at 7 and 10 days after instillation of the test material. All the test eyes were examined for the presence of corneal ulcerations at 24 hours with 2% sodium fluorescein. Those eyes with ulcerations were restained during each observation period until the ulceration healed. Clinical observations were recorded at approximately 1- and 4-hours after dosing and daily thereafter except on the weekend for the remainder of the study. Body weights were not recorded. All animals were sacrificed by over-exposure to carbon dioxide on day 10. Slight corneal opacities and iridial irritation was observed in 3/6 animals and moderate to severe conjunctival irritation in all animals at 1 hour. Corneal opacities were present in all animals at 24 hours along with corneal ulcerations. The number of corneal opacities decreased to 3/6 at 48 hours, 1/6 at 72 hours, and 0/6 by day 7. The number of corneal ulcerations decreased to 3/6 at 48 hours and 0/6 at 72 hours. Moderate to severe conjunctival irritation was still present at 24 hours and diminished slowly over the remainder of the study. The 24-hour mean Draize score was 33.0/110. The mean EC (24-,48-, and 72-hour) ocular irritation scores were 0.8 for corneal opacity, 0.0 for iritis; 2.0 for conjunctival redness; and 2.5 for conjunctival swelling. Soft stool was noted in all animals on day 1 and in 2/6 animals on day 2. Decreased food consumption and decreased fecal output were noted in 2/6 animals on days 2 and 6, respectively. No other clinical observations were noted.