Octanoic acid, 6,8-dimercapto-

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

21.07.1999 - 25.07.1999

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 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye 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 3
- Storage condition of test material: room temperature in the dark under nitrogen

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 to 16 weeks old
- Weight at study initiation: 2.78 kg
- Housing: housed in a suspended metal cage
- Diet: ad libitum, Stanrab SQC Rabbit Diet, Special Diets Services, Witham, Essex, UK
- Water: ad libitum
- Acclimation period: at least five days

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

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,1 mL of the test substance

Duration of treatment / exposure:

no data

Observation period (in vivo):

The animal was killed for humane reasons four days after treatment. An additional observation was performed immediately prior to termination.

Number of animals or in vitro replicates:

one male

Details on study design:

SCORING SYSTEM: Draize Scale for Scoring Ocular Irrritation
1. CONJUNCTIVAE
a) Redness (refers to palpebral and bulbar conjunctivae exluding cornea and iris)
0: Vessels normal
1: Vessels definitely injected above normal
2: More diffuse, deeper crimson red, individual vessels not easily discernible
3: Diffuse beefy red
b) Chemosis
0: No swelling
1: Any Swelling above normal (includes nictitating membrane)
2: Obvious swelling with partial eversion of lids
3: Swelling with lids about half closed
4: Swelling with lids half closed to completely closed
c) Discharge
0: No discharge
1: Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2: Discharge with moistening of the lids and hairs just adjacent to lids
3: Discharge with moistening of the lids and hairs a considerable area around the eye
THE TOTAL SCORE = (A + B + C) x 2 MAXIMUM TOTAL = 20

2. IRIS
d) Values
0: Normal
1: Folds above normal, congestion, swelling, circumcorneal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive
2: No reaction to light, haemorrhage, gross destruction (any or all of these)
THE TOTAL SCORE = D x 5 MAXIMUM TOTAL = 10

3. CORNEA
e) Degree of Opacity (most dense area used)
0: No opacity
1: Scattered or diffuse areas, details of iris clearly visible
2: Easily discernible translucent areas, details of iris slightly obscured
3: Opalescent areas, no details of iris visible, size of pupil barely discernible
4: Opaque, iris not discernible through the opacity
f) Area of Cornea Involved
1: One quarter (or less) but not zero
2: Greater than one quarter but less than half
3: Greater than half but less than three quarters
4: Greater than three quarters, up to whole area
THE TOTAL SCORE = (E x F) x5 MAXIMUM TOTAL = 80

MAXIMUM TOTAL SCORE POSSIBLE = 100

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 30 - <= 40

Max. score:

40

Reversibility:

not specified

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 5

Max. score:

5

Reversibility:

not specified

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

>= 14 - <= 16

Max. score:

16

Reversibility:

not specified

Any other information on results incl. tables

Interpretation of Results (Classification According to a Modified Version of the Kay and Calandra System):

The numerical values corresponding to the tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letter A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the iris designated by the letter E (degree of opacity) and F (area of opacity). For each tissue the score was calculated as follows:

Score for conjunctivae = (A+B+C) x 2

Score for iris = Dx5

Score for cornea = (ExF) x 5

Using the numerical data obtained a modified version of the system described by Kay J H and Calandra J C, J. Soc. Cosmet. Chem., 1962 13 281- 289 was used to classify the ocular irritancy potential of the test material. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point. The total score enabled assessment of the eye irritancy potential of the test material.

If the rabbit shows irriversible ocular damage the test material will be classified as corrosiv to the eye.

Results:

Individual and total scores for ocular irritation are give in Table 1.

Table 1: Indivídual and total scores for ocular irritation.

Rabbit Number and Sex (Bodyweight kg)	IPR = 0 +
	192 Male (2.78)
Time after Treatment	1 hour	24 hours	48 hours	72 hours	4 days K
CORNEA E = Degree of Opacity F = Area of Opacity	2 3	2SI 4	3SI* 4	3SI* 4	3SI* 4
Score (E x F) x 5	30	40	40	40	40
IRIS D	1	1	1	1	1
Score (D x 5)	5	5	5	5	5
CONJUNCTIVAE A = Redness B = Chemosis C = Discharge	2 2 3	2AI 3 3	3AI 2 3	3AI 2 3	3AI 2 3
Score (A + B + C) x 2	14	16	16	16	16
Total Score	49	61	81	81	81

IPR = initial pain reaction; AI = alopecia; SI = sloughing of the cornea; K = animal killed for humane reasons;

* = grade 3 opacity around lower outer edge of cornea with grade 1opacity over rest of cornea; + = one drop of Ophthaine instilled into both eyes 1 to 2 minutes before dosing

Translucent corneal opacity was noted in the treated eye one hour after treatment and at the 24 -hour observation with opalescent corneal opacity at the 48, 72- hour and 4 -day observations.

Iridial inflammation was noted in the treated eye one hour after treatment and at subsequent 24, 48, 72 -hour and 4 -day observations.

Moderate conjunctival irritation was noted in the treated eye one hour after treatment with severe conjunctival irritation at subsequent 24, 48, 72 and 4 -day observations.

Sloughing of the cornea was noted in the treated eye with alopecia around the treated eye at 24, 48, 72 -hour and 4 -day observations.

The animal was killed, for humane reasons four days after treatment.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Dihydrolipoic Acid produced a maximum total score of 81.0 and was considered to be at least a very severe irritant (Class 7 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system (based on one rabbit only).

Executive summary:

In order to assess the irritancy potential of Dihydrolipoic Acid to the eye of the New Zealand White rabbit a study according to OECD 405 ("Acute Eye Irritation/Corrosion") and 92/69EEC B.5 was performed.

A single instillation of the test material to the non-irrigated eye of one rabbit produced opalescent corneal opacity, iridial inflammation and severe conjunctival irritation. Sloughing of the cornea and alopecia were also noted. The animal was killed for humane reasons four days after treatment. In the test Dihydrolipoic Acid produced a maximum total score of 81.0 and was considered to be at least a very severe irritant (Class 7 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system (based on one rabbit only).