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

Skin irritation / corrosion

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

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

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

287-820-4

EC Name:

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

Cas Number:

85586-18-1

Molecular formula:

Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance)

IUPAC Name:

(Z,9Z)-N-(2-{2-[(8Z)-heptadec-8-en-1-yl]-4,5-dihydro-1H-imidazol-1-yl}ethyl)octadec-9-enimidic acid; 3-[(2-carboxyethyl)({2-[3-(2-carboxyethyl)-2-[(8Z)-heptadec-8-en-1-yl]imidazolidin-1-yl]ethyl})amino]propanoic acid; 3-{2-[(8Z)-heptadec-8-en-1-yl]-3-{2-[(E)-[(9Z)-1-hydroxyoctadec-9-en-1-ylidene]amino]ethyl}imidazolidin-1-yl}propanoic acid

Test animals

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.

Test system

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

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 4 hours

Score:

0.8

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 hour

Score:

2

Max. score:

2

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24 hour

Score:

1.3

Max. score:

2

Reversibility:

fully reversible

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 48 Hour

Score:

< 1

Max. score:

1

Reversibility:

fully reversible

Results 5

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 72 Hour

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 6

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1 hour

Score:

1.33

Max. score:

2

Reversibility:

fully reversible

Results 7

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24 hour

Score:

< 1

Max. score:

1

Reversibility:

fully reversible

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 48 hour

Score:

0

Reversibility:

fully reversible

Results 9

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 72 hour

Score:

0

Reversibility:

fully reversible

Results 10

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

male

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Results 11

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

male

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 12

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

male

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 13

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

male

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible

Results 14

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

male

Time point:

48 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Results 15

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

male

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 16

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

female

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Results 17

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

female

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 18

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

female

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 19

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

male

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Results 20

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

male

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Results 21

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

male

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Results 22

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

male

Time point:

24 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Results 23

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

male

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 24

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

male

Time point:

72 h

Score:

0

Max. score:

0

Reversibility:

fully reversible

Results 25

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

female

Time point:

24 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Results 26

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

female

Time point:

48 h

Score:

0

Max. score:

0

Reversibility:

other: N/A

Results 27

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.

Any other information on results incl. tables

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

Applicant's summary and conclusion

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.