bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Remarks:

study was conducted prior to the implementation of REACH and adoption of suitable in vitro methods

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-10-31 - 1995-11-10 (experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

OECD Guide!ine for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion". Adopted: 17 July 1992.

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide

EC Number:

605-708-9

Cas Number:

174125-93-0

Molecular formula:

n.a.

IUPAC Name:

bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide

Test material form:

liquid

Remarks:

Orange/brown

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Froxfield (U.K.) Ltd., Petersfield, Hampshire, England
- Age at study initiation: approx. 10 to 11 weeks
- Weight at study initiation: 2.3 to 2.5 kg
- Housing: The rabbits were selected without conscious bias for the study. They were housed individually in metal cages with perforated floors.
- Diet (e.g. ad libitum): A standard laboratory diet SDS Stanrab (P) Rabbit Diet was provided ad libitum.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: All rabbits were acclimatised to the experimental environment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Animal room temperature was maintained at approximately 19°C.
- Humidity (%): Relative humidity was maintained at 30 ± 70%.
These environmental parameters were recorded daily.
- Air changes (per hr): Air exchange was maintained at approximately 19 air changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a time switch to give 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period.

The albino rabbit was chosen as it has been shown to be a suitable model for skin irritation studies and is the animal recommended in the test guideline.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

4h exposure

Observation period:

11 days

Number of animals:

Three healthy adult rabbits

Details on study design:

TEST SITE
- Area of exposure: Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 100 mm x 100 mm.
- Type of wrap if used: A 0.5 ml amount of the test substance was applied under a 25 mm x 25 mm gauze pad to one intact skin site on each animal.
Each treatment site was covered with "Elastoplast" elastic adhesive dressing for four hours. The animals were not restrained during the exposure period and were returned to their cages immediately after treatment.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed with warm water (30° to 40°C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
Clinical signs: All animals were observed daily for signs of ill health or toxicity.
Dermal responses: Examination of the treated skin was made on Day 1 (ie approximately 60 minutes after removal of the dressings) and on Days 2, 3 and 4 (equivalent to 24, 48 and 72 hours after exposure). Additional observations were made on Days 5 through to 11.

SCORING SYSTEM:
Local dermal irritation was assessed using the prescribed numerical system:
Erythema and eschar formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) preventing erythema reading 4
Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4
Any other lesion not covered by this scoring system, was described.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: day 11

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: day 11

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: day 11

Results 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.56

Max. score:

2

Reversibility:

fully reversible within: day 11

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: day 3

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible within: day 4

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

Results 8

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: day 4

Irritant / corrosive response data:

Very slight to well-defined erythema with or without very slight to slight oedema was seen in all three animals. These reactions gradually ameliorated but slight erythema together with dryness and sloughing of the stratum corneum was still present in all three animals from Day 8. The skins were all normal on Day 11.

Other effects:

- Other adverse local effects: Dryness and sloughing
- Other adverse systemic effects: none stated

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

EU implementation

Conclusions:

The study was conducted under GLP according to OECD TG 404 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies. Hence, the results can be considered as sufficiently reliable to assess the irritating properties of the test item.
Testing revealed the following scores from gradings at 24, 48 and 72 hours in the three individual animals: 1.0 / 1.67 / 2.0 (erythema score) and 0.33 / 0.67 / 0.0 (edema score). These reactions gradually ameliorated but slight erythema together with dryness and sloughing of the stratum corneum was still present in all three animals from Day 8, all effects were fully reversible on day 11.
According to Regulation (EC) 1272/2008 table 3.2.2, a substance must be classified as Irritating to skin (Category 2), if the following criteria are met:
1) Mean value of ≥ 2,3 - ≤ 4,0 for erythema/ eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal or, if reactions are delayed, from grades on 3 consecutive days after the onset of skin reactions; or
(2) Inflammation that persists to the end of the observation period normally 14 days in at least 2 animals, particularly taking into account alopecia (limited area), hyperkeratosis, hyperplasia, and scaling; or
(3) In some cases where there is pronounced variability of response among animals, with very definite positive effects related to chemical exposure in a single animal but less than the criteria above.
Hence, the above mentioned criteria for classification according to Regulation (EC) 1272/2008 as skin irritant are not met.

Executive summary:

A study was performed to assess the skin irritation potential of Bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide to the rabbit. The method followed was that described in: OECD Guideline for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion". Adopted: 17 July 1992.

Three rabbits were each administered a single dermal dose of 0.5 ml of the test substance and observed for eleven days.

A single semi-occlusive application of the test item to intact rabbit skin for four hours elicited well-defined dermal irritation. All reactions had resolved by Day 11. Testing revealed the following scores from gradings at 24, 48 and 72 hours in the three individual animals: 1.0 / 1.67 / 2.0 (erythema score) and 0.33 / 0.67 / 0.0 (edema score).

The substance does not need to be classified as skin irritant according to Regulation (EC) 1272/2008.