Octanoic acid, 6,8-dimercapto-

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

24.06.1999 - 20.07.1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

6,8-disulfanyloctanoic acid

IUPAC Name:

6,8-disulfanyloctanoic acid

Constituent 2

Reference substance name:

6,8-disulfanyloctanoic acid

Cas Number:

462-20-4

Molecular formula:

C8H16O2S2

IUPAC Name:

6,8-disulfanyloctanoic acid

Constituent 3

Reference substance name:

6,8-disulfanyloctanoic acid

EC Number:

610-288-5

Cas Number:

462-20-4

Molecular formula:

C8H16O2S2

IUPAC Name:

6,8-disulfanyloctanoic acid

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Dihydrolipoic Acid
- Physical state: liquid
- Lot/batch No.: TC 3 KD
- Storage condition of test material: room temperature in the dark, under nitrogen

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12- 16 weeks
- Weight at study initiation: 2.55 - 282 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum; Stanrab SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK
- Water: ad libitum
- Acclimation period: minimum five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23 °C
- Humidity (%): 30 -70 %
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12 hours continous light and 12 hours darkness.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,5 mL of the test substance

Duration of treatment / exposure:

three time points: 3 minutes, 1 hour and 4 hours

Observation period:

14 days

Number of animals:

three males

Details on study design:

TEST SITE
- Area of exposure: dorsal flank area
- Type of wrap if used: elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4hours

SCORING SYSTEM:
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.
Erythema and Eschar Formation:
0: No erythema
1: Very slight erythema (barely perceptible)
2: Well-defined erythema
3: Moderate to severe erythema
4: Severe erythema (beet redness) to slight eschar formation (injuries in depth)
Oedema Formation:
0: No oedema
1: Very slight oedema (barely perceptible)
2: Slight oedema (edges of area well-defined by definite raising)
3: Moderate oedema (raised approximately 1 millimeter)
4: Severe oedema (raised more than 1 millimeter and extending beyond the area of exposure

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

6

Max. score:

6

Reversibility:

not specified

Remarks on result:

probability of moderate irritation

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

>= 6

Max. score:

6

Reversibility:

not specified

Remarks on result:

probability of moderate irritation

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

>= 5

Max. score:

5

Reversibility:

not specified

Remarks on result:

probability of moderate irritation

Any other information on results incl. tables

Interpretation of Results (Calculation of Primary Irritation Index and Grading of the Irritancy Potential Using Draize Scheme):

The score of the erythema and oedema at the 24 and 72 -hour readings (4 -hour exposure) were totalled for the three 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 Daize 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

Results of 4 -hour exposure period:

Table 1: The individual scores for erythema/eschar and oedema of the 4 -hour exposure period.

Skin Reaction	Observation Time	Individual Scores - Rabbit Number, Sex and Bodyweight			Total
		134 Male (2.82 kg)	1 Male (2.55 kg)	2 Male (2.64 kg)
Erythema/Eschar Formation	1 hour	2 (N)	3	2	(7)
	24 hours	2 (N)	2	2	6
	48 hours	2 (N)	2	2	(6)
	72 hours	2 LeLf(N)	2 Le	1 Le	5
	7 days	0 Cf(Sp)	0 Cf	0 D	(0)
	14 days	0 Fr(G)	0	0	(0)
Oedema Formation	1 hour	3	3	3	(9)
	24 hours	3 Oe	3	2	8
	48 hours	2	2	2	(6)
	72 hours	2	2	1	5
	7 days	0	0	0	(0)
	14 days	0	0	0	(0)
Sum of 24 and 72-hour readings (S)	24
Primary Irritation Index (S/6)	24/6 = 4.0
Classification	Moderate Irritant

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

Cf = Crust formation

D = slight desquamation

Fr = reduced regrowth of fur

(G) = glossy skin where necrosis and straw-coloured scabbing previously located

Le = loss of skin elasticity

Lf = loss of skin flexibility

(N) = narrow margin of green-coloured dermal necrosis (approx. 2 mm wide) running along bottom edge of treatment side. Grade 2 erythema present over treated area

Oe = oedema extending ventrally below treatment site

(Sp) = area of straw-coloured scabbing where necrosis previously located

Results of the 1 -hour exposure period:

Table 2: The individual scores for erythema/eschar and oedema of the 1 -hour exposure period.

Skin Reaction	Observation Time	Individual Scores - Rabbit Number, Sex and Bodyweight
		134 Male (2.82 kg)
		3-minute exposure	1-hour exposure
Erythema/Eschar Formation	1 hour	0	0
	24 hours	0	2
	48 hours	0	2
	72 hours	0	2 Le
	7 days	0	0 Cf
	14 days	0	0
Oedema Formation	1 hour	0	0
	24 hours	0	2
	48 hours	0	1
	72 hours	0	1
	7 days	0	0
	14 days	0	0

Cf = crust formation

Le = loss of skin elasticity

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

Dihydrolipoic Acid produced a primary irritation index of 4.0 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.

Executive summary:

A study (according to OECD 404 and 92/69/EEC B.4) was performed to assess the irritancy potential of Dihydrolipoic Acid to the skin of the New Zealand White rabbit.

A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined to moderate to severe erythema and moderate oedema. A thin margin of green-coloured dermal necrosis (approx. 2 mm wide) was noted adjacent to the lower edge of one treatment site with loss of skin elasticity and flexibility, crust formation, reduced regrowth of fur, an area of straw-coloured scabbing, glossy skin and oedema extending ventrally below the treatment site were also noted. Two treated skin sites appeared normal at the 14 -day observation. No evidence of full thickness tissue destruction was noted. 3 -minute and 1 -hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects.

Dihydrolipoic Acid produced a primary irritation idex of 4.0 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme.