L-97-034-PB

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29th January - 5th February 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pentaerythritol mixed esters with 2-methyl butyric acid, n-pentanoic acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid, n-decanoic acid

Cas Number:

141686-49-9

IUPAC Name:

Pentaerythritol mixed esters with 2-methyl butyric acid, n-pentanoic acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid, n-decanoic acid

Constituent 2

Reference substance name:

Trimethylol propane mixed esters with 2-methyl butyric acid, n-pentanoic acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid, n-decanoic acid

Cas Number:

141686-50-2

IUPAC Name:

Trimethylol propane mixed esters with 2-methyl butyric acid, n-pentanoic acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid, n-decanoic acid

Test material form:

liquid

Details on test material:

Identification: Hatcol ® 1772
Appearance/physical state: Clear colorless liquid
Purity: 100% (no solvent present)
Composition: 70% pentaerythritol esters described by CAS# 141686-49-9; 30% trimethylolpropane esters described by CAS# 141686-50-2

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

ANIMAL INFORMATION
Three New Zealand White rabbits supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK were used. At the start of the study the animals weighed 2.54 to 2.66 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

ANIMAL CARE AND HUSBANDRY
The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK) was allowed throughout the study.

The animal room was maintained at a temperature of 18 to 20°C and relative humidity of 48 to 58%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.5 ml of test material

Duration of treatment / exposure:

4 hours

Observation period:

7 day

Number of animals:

3

Details on study design:

PROCEDURE
On the day before the test each rabbit 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. On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 ml of the test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in a position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals intefering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals returned to their cages for the duration of the exposure period. Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits. 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 from Draize J H, (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.

INTERPRETATION OF RESULTS
The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the three test rabbits (12 values) and this total was divided by six to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by Draize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p.47.

Primary Irritation Index Classification of Irritancy
0 Non-irritant
>0 to 2 Mild irritant
>2 to 5 Moderate irritant
>5 to 8 Severe irritant

If irreversible alteration of of the dermal tissue is noted in any rabbit, as judged by the Study Director, which may include ulceration and clear necrosis or signs of scar tissue, the test material is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible

Remarks on result:

other:

Remarks:

Treated skin site appeared normal at the 7-day observation.

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.3

Reversibility:

fully reversible

Remarks on result:

other:

Remarks:

Treated skin site appeared normal at the 7-day observation.

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible

Remarks on result:

other:

Remarks:

Treated skin site appeared normal at the 7-day observation.

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

other:

Remarks:

Treated skin site appeared normal at the 7-day observation.

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Reversibility:

fully reversible

Remarks on result:

other:

Remarks:

Treated skin site appeared normal at the 7-day observation.

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

other:

Remarks:

Treated skin site appeared normal at the 7-day observation.

Any other information on results incl. tables

Table 1: Individual skin reactions

Skin Reaction	Observation Time	Individual Scores - Rabbit Number and Sex (bodyweight kg)			Total
		92 Male (2.66)	81 Male (2.60)	141 Male (2.54)
Erythema/eschar formation	1 hour	0	1	1	(2)
	24 hours	1	2	1	4
	48 hours	0	1	0	(1)
	72 hours	0	1	0	1
	7 days	1	0	0	(0)
Oedema formation	1 hour	0	1	0	(1)
	24 hours	0	1	0	1
	48 hours	0	0	0	(0)
	72 hours	0	0	0	0
	7 days	0	0	0	(0)
Sum of 24 and 72 -hour Readings (S): 6
Primary Irritation Index (S/6): 6/6 = 1.0
Classification: Mild irritant

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

Table 2: Individual daily and mean scores for dermal irritation following 4 -hour exposure required for EU labelling regulations

Skin Reaction	Reading (hours)	Individual Scores - Rabbit Number and Sex (Bodyweight kg)
		92 Male (2.66)	81 Male (2.60)	141 Male (2.54)
Erythema/eschar formation	24	1	2	1
	48	0	1	0
	72	0	1	0
Total		1	4	1
Mean Score		0.3	1.3	0.3
Oedema formation	24	0	1	0
	48	0	0	0
	72	0	0	0
Total		0	1	0
Mean Score		0.0	0.3	0.0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material produced a primary irritation index of 1.0 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. No symbol and risk phrase are required.

Executive summary:

Introduction

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992) and Method B4 of the Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC) and the US Environmental Protection Agency (EPA) OPPTS draft guidelines 870.2500.

Method

A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well-defined erythema and very slight oedema. All treated skin sites appeared normal at the 7 -day observation.

Conclusion

The test material produced a primary irritation index of 1.0 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. No symbol and risk phrase are required.