Fatty acids, C18-unsatd., reaction products with acrylic acid and polyethylenepolyamines

Endpoint summary

Description of key information

Irritation index = 0.8; OECD 404 (2002); Allen D, 2000.

Maximum score for conjuctival endpoints over 72 hours = 2, no irritis was or corneal opacity was observed. OECD 405 (1987); Allen D, 2000

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:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted in accordance with international guidelines and in accordance with GLP. All relevant validity criteria were met.

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 (incl. QA statement)

Remarks:

UK GLP Monitoring authority

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand white supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK were used. At the start of the study the animals weighed 2.44 to 2.68 Kg and were twelve to sixteen weeks old. After a minimal acclimatization period of five days each animal was given a unique study number, which was written with a black indelible marker pen on the inner surface of the ear and the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (Stanrab SQC rabbit diet) from Special Diets Lrd, Witham, Essex was allowed throughout the study

The temperature and relative humidity were set to achieve limits of 17 to 23 degrees centigrade and 30 and 70 percent respectively. Any occasional deviations were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately 15 changes per hour and lighting was controlled to give twelve hours continuous light and twelve hours of darkness.

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5ml of test material

Duration of treatment / exposure:

Animals were exposed for three time points 3 minutes, one hour and four hours after application

Observation period:

24, 48 and 72 hours post exposure

Number of animals:

Three

Details on study design:

On the day before the test each animal was clipped free of fur from the dorsal flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.

One rabbit was initially tested. Three suitable test sites were selected on the back of the rabbit. At each test site a quantity of 0.5ml of the test material were introduced under 2.5 cm by 2.5cm cotton gauze patch and placed in position on the shorn skin. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the truck of the rabbit was wrapped in an elasticated corset and the animal was returned to its cage of the duration of the exposure period.

One patch was removed at each of three time points; 3 minutes, 1 hour and four hours after application. Any residual test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial methylated spirits.

After consideration of the skin reactions in the first animal two additional animals were treated with 0.5 ml of test material. One patch was applied to the back of each animal and was allowed to remain in contact with the skin for a period of four hours.

Approximately one hour following the removal of the patches and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the scale developed by Draize JH (1977) Dermal and eye toxicity test In Principles and procedures for evaluation the toxicity of household substances, National Academy of Sciences, Washington DC P.31

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4 hours

Score:

0.8

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 hour

Score:

2

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 hour

Score:

1.3

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48 Hour

Score:

< 1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 Hour

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1 hour

Score:

1.33

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 hour

Score:

< 1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48 hour

Score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 hour

Score:

0

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

male

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

male

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

male

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

male

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

male

Time point:

48 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

male

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

female

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

female

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

female

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

male

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

male

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

male

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

male

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

male

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

male

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

female

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

female

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

female

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritant / corrosive response data:

Well defined erythema was noted on all treated skin sites at the one hour observation, with slight to well defined erythema at the 24-hour observation. Very slight erythema was noted at one treated skin at the 48-hour observation. Full recovery was noted in all animals at the 72-hour observation.

Very slight to slight edema was noted in all treated skin sites at the 1-hour observation, very slight edema was noted at one treated skin site at the 24-hour observation, with full recovery by the 48-hour observation.

All treated skin sites appeared normal at the 72-hour observation.

The Primary irritation index was calculated to be 0.8 and the test substance was judged to be not irritating in accordance with EU labelling requirements.

Other effects:

One animal was also concurrently exposed to test material at two seperate sites for shorter exposure durations. These were 3 minutes and one hour. The animal was observed and scored at 1-hr, 24-hr, 48-hr and 72-hr post exposure.

With an exposure period of 3 minutes no evidence of skin irritation was noted during the study.
With an exposure period of 1-hour; very slight erythema was noted at the treated skin site at the 1-hr observation only. Treated skin appeared normal at the 24-hour obeservation.

Individual skin reactions following 4 -hour exposure period

Skin reaction	Observation period	Individual Scores - Rabbit # and sex (Bodyweight Kg)			Total
		106 Male (2.68 kg)	10 Male (2.66 kg)	12 Female 2.44 kg)
Erythema / Eschar formation	1 hour 24 hours 48 hours 72 hours	2 1 0 0	2 2 1 0	2 1 0 0	(6) 4 (1) 0
Edema formation	1 hour 24 hours 48 hours 72 hours	1 0 0 0	2 1 0 0	1 0 0 0	(4) 1 (0) 0
Sum of 24 and 72 hour readings (S)	5
Primary Irritation index S/6	5/6 = 0.8
Classification	Mild irritant

( ) = Total values not used for calculation of Primary irritation index

Indvidual daily and mean scores for dermal irritation following 4 -hour exposure required for EU Labelling

Skin reaction	Observation period	Individual Scores - Rabbit # and sex (Bodyweight Kg)
		106 Male (2.68 kg)	10 Male (2.66 kg)	12 Female 2.44 kg)
Erythema / Eschar formation	24 hours 48 hours 72 hours	1 0 0	2 1 0	1 0 0
Total	-	1	3	1
Mean score	-	0.3	1	0.3
Oedema formation	24 hours 48 hours 72 hours	0 0 0	1 0 0	0 0 0
Total	-	0	1	0
Mean score	-	0	0.3	0

Individual skin reactions following 1-hr and 3-minute exposures

Skin reaction	Observation period	Individual Scores - Rabbit # and sex (Bodyweight Kg)
		106 Male (2.68 kg)
		1 hour exposure	3 minute exposure
Erythema / Eschar formation	1 hour 24 hours 48 hours 72 hours	1 0 0 0	0 0 0 0
Oedema formation	1 hour 24 hours 48 hours 72 hours	1 0 0 0	0 0 0 0

Interpretation of results:

GHS criteria not met

Conclusions:

The test material PR-4758 , produced a primary irritation index of 0.8 and was classified as a MILD IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations.

Executive summary:

At the request of Nalco Exxon, Safepharm Laboratories performed an acute dermal irritation test in the New Zealand White rabbit in accordance with OECD guideline 404 and EU method B4 and in compliance with Good laboratory practice. Three animals were used in the study and the effects of PR-4758 were determined following a 4 -hour exposure period of intact semi-occluded skin with observation and scoring to the Draize JH scheme at 1-hr, 24-hour, 48-hour and 72-hours.

The primary irritation index was determined to be 0.8 and PR-4758 is accordingly classified as a MILD SKIN IRRITANT to rabbit skin by the Draize scoring methodology. Irritation is insufficient to meet EU labelling requirements.

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:

2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted in accordance with international guidelines and in accordance with GLP.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

UK GLP Monitoring authority

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three New Zealand white supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK were used. At the start of the study the animals weighed 2.65 to 2.74 Kg and were twelve to sixteen weeks old. After a minimal acclimatization period of five days each animal was given a unique study number, which was written with a black indelible marker pen on the inner surface of the ear and the cage label.

The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (Stanrab SQC rabbit diet) from Special Diets Lrd, Witham, Essex was allowed throughout the study

The temperature and relative humidity were set to achieve limits of 17 to 23 degrees centigrade and 30 and 70 percent respectively. Any occasional deviations were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately 15 changes per hour and lighting was controlled to give twelve hours continuous light and twelve hours of darkness.

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

A volume of 0.1ml undiluted test material

Duration of treatment / exposure:

1 second

Observation period (in vivo):

Assessment of occular damage/irritation was made approximately 1-hour, 24, 48, 72 hours and 7 days following treatment

Number of animals or in vitro replicates:

Three

Details on study design:

One animal was initially treated. A volume of 0.1ml of the test material was instilled into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after instillation, to prevent loss of the test material and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made.
After consideration of the ocular response produced in the first treated animal, an additional two animals were treated in a similar fashion. However in order to minimize pain on instillation of the test material, one drop of local anaesthetic (Ametocaine Hydrochloride 0.5%, Chauvin Pharmaceuticals, Romford, Essex, UK) was instilled into both eyes of these animals 1 to 2 minutes before treatment.
Assessment of ocular damage/irritation was made approximately 1-hour, 24, 48 and 72 hours following treatment. Ocular irritation was assessed using the methodology developed by Draize JH (1977) and reported in “Dermal and eye toxicity tests” In: Principles and Procedures for evaluating the toxicity of Household substances National Academy of Sciences, Washington DC P. 48-49.
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.
An additional observation was made in one treated eye on Day 7 to assess the reversibility of the ocular effects.

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 1-hour

Score:

12

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 24-hour

Score:

9.3

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 48-hour

Score:

4

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 72-hour

Score:

0.7

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 7-day

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

female

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

female

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

female

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

female

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

female

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

female

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

female

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

iris score

Basis:

animal #1

Remarks:

female

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

female

Time point:

24 h

Score:

12

Max. score:

12

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

female

Time point:

48 h

Score:

8

Max. score:

8

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

female

Time point:

72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Remarks:

female

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

female

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

female

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

cornea opacity score

Basis:

animal #2

Remarks:

female

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

female

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

female

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

iris score

Basis:

animal #2

Remarks:

female

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

female

Time point:

24 h

Score:

8

Max. score:

8

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

female

Time point:

48 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #2

Remarks:

female

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

male

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

cornea opacity score

Basis:

animal #3

Remarks:

male

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

cornea opacity score

Basis:

animal #1

Remarks:

male

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

male

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

male

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

iris score

Basis:

animal #3

Remarks:

male

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

male

Time point:

24 h

Score:

8

Max. score:

8

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

male

Time point:

48 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

male

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

female

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

female

Time point:

48 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

female

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

female

Time point:

7 d

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

female

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

female

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #2

Remarks:

female

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

male

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Remarks:

male

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Irritant / corrosive response data:

The test material, PR-4758 produced a maximum group mean score of 12.0 and was classified as a MILD IRRITANT to the rabbit eye according to a modified Kay and Calandra classification system.

Individual and group mean scores for ocular irritation were noted during the study. No corneal or irial effects were noted. Moderate conjunctival irritation was noted in all treated eyes at 1 and 24-hour observations with minimal to moderate conjuncitval irritation at the 48-hour observation. Minimal conjuncitval redness was noted in one treated eye at the 72-hour observation.

Two treated eyes appeared normal at the 72-hour observation and one treated eye appeared normal at the 7-day observation.

Other effects:

None noted

Individual scores and individual total scores for ocular irritation

Rabbit # and Sex (Bodyweight Kg)	IPR = 3					IPR = 0 +				IPR = 0 +
	4 Female (2.74)					107 Female (2.65)				108 Male (2.66)
Time after treatment	1-hr	24-hr	48-hr	72-hr	7-day	1-hr	24-hr	48-hr	72-hr	1-hr	24-hr	48-hr	72-hr
Cornea
Degree of opacity (E)	0	0	0	0	0	0	0	0	0	0	0	0	0
Area of opacity (F)	0	0	0	0	0	0	0	0	0	0	0	0	0
Score (ExF) x 5	0	0	0	0	0	0	0	0	0	0	0	0	0
Iris
D	0	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivae
Redness (A)	2	2	2	1	0	2	2	1	0	2	2	1	0
Chemosis (B)	2	2	1	0	0	2	1	0	0	2	1	0	0
Discharge ( C )	2	2	1	0	0	2	1	0	0	2	1	0	0
Score (A+B+C) x 2	12	12	8	2	0	12	8	2	0	12	8	2	0
Total Score	12	12	8	2	0	12	8	2	0	12	8	2	0

Where IPR = Initial pain response and + = 1 drop of Amethocaine Hydrochloride instillation

Individual Total scores and group mean scores for ocular irritation

Rabbit # and Sex (Bodyweight Kg)	Individual total Scores
	1-hr	24-hr	48-hr	72-hr	7-d
4 Female (2.74)	12	12	8	2	0
107 Female (2.65)	12	8	2	0	-
108 Male (2.66)	12	8	2	0	-
Group total	36	28	12	2	0
Group mean score	12.0	9.3	4.0	0.7	0.0

- = Observation not required

Individual Mean scores for Cornea, Iris and conjunctiva

Rabbit # and Sex (Bodyweight Kg)	Time after treatment	Corneal opacity	Iridial imflammation	Conjunctival irritation	Conjunctivital chemosis
4 Female (2.74)	24-hr	0	0	2	2
	48-hr	0	0	2	1
	72-hr	0	0	1	0
	Total	0	0	5	3
	Mean	0	0	1.7	1
107 Female (2.65)	24-hr	0	0	2	1
	48-hr	0	0	1	0
	72-hr	0	0	0	0
	Total	0	0	3	1
	Mean	0	0	1	0.3
108 Male (2.66)	24-hr	0	0	2	1
	48-hr	0	0	1	0
	72-hr	0	0	0	0
	Total	0	0	3	1
	Mean	0	0	1	0.3

Interpretation of results:

GHS criteria not met

Conclusions:

The test material, PR-4758 produced a maximum group mean score of 12.0 and was classified as a MILD IRRITANT to the rabbit eye according to a modified Kay and Calandra classification system.

Executive summary:

At the request of Nalco Exxon Ltd, Safepharm Laboratories Ltd performed an acute eye irritation/corrosion study in accordance with Method B5 of Commision directive 92/69/EEC on PR-4758. The study was in compliance with Good laboratory practice. 0.1ml of PR-4758 was instilled into one eye of three healthy New Zealand White rabbits and their responses to the test material monitored and scored 1-hour, 24, 48, 72 hours and 7-days post exposure. The study indicates that PR-4758 produced a maximum group mean score of 12 and was classified as a mild irritant to the rabbit eye in accordance with the Kay and Calandra classification system.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Two key studies exist. Test material is not irritating or corrosive to skin, based on studies performed in vivo in the rabbit. Eye irration was considered mild. Both tests abide by OECD guidelines. The test were done to GLP standards in a GLP certified laboratories.

Justification for selection of skin irritation / corrosion endpoint:

Only one key study exists.  The study was conducted in accordance with OECD 404 (2002) to GLP standards within a GLP certified laboratory.

Justification for selection of eye irritation endpoint:

Only one key study exists.  The study was conducted in accordance with OECD 404 (2002) to GLP standards within a GLP certified laboratory.

Effects on respiratory irritation: no study available.

Justification for classification or non-classification

Test material is not irritating or corrosive, to skin based on studies performedin vivoin the rabbit and as such does not meet classification criteria. There was mild irratation to the eye that was fully reversible. The data were conclusive but not sufficient for classification under CLP guidance (2015).