Santicizer 2148

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-11-14 to 1990-04-30

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Version / remarks:

FIFRA: Pesticide Assessment Guidelines (Primary Dermal Irritation Study);
TSCA: Health Effects Test Guidelines (Acute Exposure, Primary Dermal Irritation)

Deviations:

not specified

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Phenol

EC Number:

203-632-7

EC Name:

Phenol

Cas Number:

108-95-2

Molecular formula:

C6H6O

IUPAC Name:

phenol

Constituent 2

Reference substance name:

1-chlorododecane

Molecular formula:

C12H25Cl

IUPAC Name:

1-chlorododecane

Constituent 3

Reference substance name:

1-Dodecanol

Cas Number:

112-53-8

Molecular formula:

C12H26O

IUPAC Name:

1-Dodecanol

Constituent 4

Reference substance name:

1-Tetradecanol

Cas Number:

112-72-1

Molecular formula:

C14H30O

IUPAC Name:

1-Tetradecanol

Constituent 5

Reference substance name:

triphenyl phosphate

Cas Number:

115-86-6

Molecular formula:

C18H15O4P

IUPAC Name:

triphenyl phosphate

Constituent 6

Reference substance name:

-

EC Number:

431-760-5

EC Name:

-

Cas Number:

27460-02-2

Molecular formula:

C24H35O4P

IUPAC Name:

dodecyl diphenyl phosphate

Constituent 7

Reference substance name:

diphenyl tetradecyl phosphate

Cas Number:

142474-86-0

Molecular formula:

C26H39O4P

IUPAC Name:

diphenyl tetradecyl phosphate

Constituent 8

Reference substance name:

Didodecyl phenyl phosphate

Cas Number:

56827-93-1

Molecular formula:

C30H55O4P

IUPAC Name:

Didodecyl phenyl phosphate

Test material form:

liquid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

6 (3 males 3 females) young adults (at least 8 weeks old at study initiation) Albino rabbits (New Zealand White) were chosen for dermal irritation studies. The New Zealand White breed was used because of its historical and because of the existing historical database for comparative evaluation. All animals were checked for viability twice daily. Prior to assignment to study all animals were examined to ascertain suitability for study.
The rabbits were individually housed in suspended, stainless steel with wire mesh bottoms in a temperature (60-70°F – monitored and recorded twice daily) and humidity (30-70% - monitored and recorded daily) controlled room with a 12 hour light, 12 hour dark cycle controlled by an automatic timer.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

0.5 mL of test material per site (the material was applied to two intact sites on eachO animal)

Duration of treatment / exposure:

single 4 hour exposure

Observation period:

7-14 days

Number of animals:

6

Details on study design:

On the day before dosing, the hair of each rabbit was clipped from the dorsal area of the trunk with an electric clipper so as to expose at least 10% of the body surface area, Care was taken to avoid abrading the skin. Only animals with intact, healthy skin were used.

The test material was administered as received. An appropriate amount of the test material was applied beneath a gauze square 1'' x 1'', placed directly on the test site and held in place with tape and a semi-occlusive covering. Elizabethean collars were placed on each animal prior to or at the time of dosing in order to prevent the animal from disturbing the wrapping and test sites.

Following 4 hours of exposure, the wrappings and gauze squares were removed and the test site was gently wiped free of excess test material using water and gauze. After approximately 30 minutes, dermal observations were made and scoring done according to the method of Draize.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 24/72 hr

Score:

2.1

Reversibility:

not fully reversible within: 14 days

Remarks:

5 of the 6 animals were free of signs of dermal irritation. 1 animal continued to exhibit very slight (barely perceptible) dermal irritation at study termination.

Remarks on result:

probability of mild irritation

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

4

Results 3

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

4

Irritant / corrosive response data:

All six animals exhibited slight erythema with little or no edema. By Day 14, 5 of the 6 animals were free of signs of dermal irritation while 1 animal continued to exhibit very slight (barely perceptible) dermal irritation at study termination.

Any other information on results incl. tables

Table 1. Primary dermal irritation study in rabbits (4-hour exposure/semi-occlusive covering)

Time interval^b	Patch Sites & Observations		Animal Number and Sex						Mean Score
			8648F	8649M	8650F	8651M	8652F	8563M
0.5 Hours	Right	ER	0	1	1	0	1	0	-
		ED	0	0	0	0	0	0
		Other	-	-	-	-	-	-
	Left	ER	0	1	0	0	1	0
		ED	0	0	0	0	0	0
		Other	-	-	-	-	-	-
24 Hours	Right	ER	2	2	2	2	2	2	2.0
		ED	0	0	0	0	0	0	0.0
		Other	-	-	-	-	-	-	-
	Left	ER	2	2	2	2	2	2	2.0
		ED	0	1	0	0	0	1	0.3
		Other	-	-	-	-	-	-	-
48 Hours	Right	ER	2	2	2	2	2	2	-
		ED	0	0	0	0	0	0
		Other	-	-	-	-	-	-
	Left	ER	2	2	2	2	2	2
		ED	0	0	0	0	0	0
		Other	-	-	-	-	-	-
72 Hours	Right	ER	2	2	2	2	2	2	2.0
		ED	0	0	0	0	0	0	0.0
		Other	-	-	-	-	-	-	-
	Left	ER	2	2	2	2	2	2	2.0
		ED	0	0	0	0	0	0	0.2
		Other	-	-	-	-	-	-	-
Day 7	Right	ER	2	0	0	2	2	2	N/A
		ED	0	0	0	0	0	0
		Other	D	-	-	-	-	-
	Left	ER	2	0	0	2	2	1
		ED	0	0	0	0	0	0
		Other	0	-	0	-	-	-
Day 10	Right	ER	0	-	-	1	0	1
		ED	0	-	-	0	0	0
		Other	D	-	-	-	-	-
	Left	ER	0	-	-	1	0	1
		ED	0	-	-	0	0	0
		Other	D	-	-	-	-	-
Day 14	Right	ER	-	-	-	1	-	0
		ED	-	-	-	0	-	0
		Other	-	-	-	-	-	-
	Left	ER	-	-	-	0	-	0
		ED	-	-		0	-	0
		Other	-	-		0	-	-

^b Time indicated is time from patch removal

M = male; F = female; ER = Erythema; ED = Edema; D = Desquamation

Sum of means = 8.5

Average Dermal irritation score = 2.1

Applicant's summary and conclusion

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

All 6 animals exhibited slight erythema with little or no edema. By Day 14, 5 of 6 animals were free of signs of dermal irritation; one animal continued to exhibit very slight (barely perceptible) dermal irritation at study termination (Day 14)

It was therefore concluded that XP-2563 produced mild by generally reversible dermal irritation. The average dermal irritation score of XP-2563 is 2.1 Animal experience or test data that indicates that the substance/mixture causes reversible damage to the skin following exposure of up to 4 hours, mean value of ≥1.5 < 2.3 for erythema/eschar in 2 of 3 tested animals.

Executive summary:

This study was intended to provide information on the health hazards likely to arise from a short-term accidental exposure to the test material by the dermal route. 6 (3 males 3 females) young adults (at least 8 weeks old at study initiation) Albino rabbits (New Zealand White) were chosen for dermal irritation studies. XP-2563 was applied to two intact sites on each animal, with a dosage of 0.5 ml per site, for an exposure period of approx. 4 hours under semi-occlusive conditions.

The results showed that all 6 animals exhibited slight erythema with little or no edema. By Day 14, five of six animals were free of signs of dermal irritation; one animal continued to exhibit very slight (barely perceptible) dermal irritation at study termination (Day 14)

It was therefore concluded that XP-2563 produced mild by generally reversible dermal irritation. The average dermal irritation score of XP-2563 is 2.1.