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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
According to the later amendment of REACH, i.e. Commission Regulation (EU) 2016/863 of 31 May 2016, testing by the dermal route does not need to be conducted if: — the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and — no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation) or, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read across, QSAR studies). The oral LD50 in rats is >2000 mg/kg, no animal died at a dose of 2000 mg/kg, clinical signs were Piloerection which persisted and was accompanied in all animals on Day 2 only by soft to liquid faeces. There were no other clinical signs and recovery, as judged by external appearance and behaviour, was complete in all instances by Day 3. In the available OECD 404 skin irritation study, there were no signs of toxicity or ill health in any rabbit during the observation period. Further, in the available GPMT, also no signs of ill health or toxicity were recorded. Hence, testing can be waived.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Remarks:

OECD 401

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-11-02 - 1995-11-16 (Experimental phase)

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

OECD Guideline for Testing of Chemicals No. 401 "Acute Oral Toxicity". Adopted: 24 February 1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

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

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Hsd/Ola:Sprague-Dawley(CD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Olac Ltd., Bicester, Oxon, England
- Age at study initiation: approximately four to seven weeks
- Weight at study initiation: 100 to 118 g
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 2 hours after dosing.
- Housing: The rats were allocated without conscious bias to cages within the treatment groups. They were housed in groups of up to five rats of the same sex in metal cages with wire mesh floors.
- Diet (e.g. ad libitum): A standard laboratory rodent diet (SDS LAD 1) was provided ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: All the rats were acclimatised to the experimental environment for a period of seven days prior to the start of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Animal room temperature was set to achieve a temperature of 22 + 3°C.
- Humidity (%): Relative humidity was not controlled but was anticipated to be in the range 30 - 70% RH.
Permanent daily recordings of these parameters were made and these are archived with other Department raw data. Any slight deviation in temperature and humidity that may have occurred was not considered to have affected the integrity or validity of the study
- Air changes (per hr): Air exchange was maintained at 10 to 15 air changes per hour.
- Photoperiod (hrs dark / hrs light): Lighting was controlled by means of a lime switch to provide 12 hours of artificial light (0700 ― 1900 hours) in each 24-hour period.

The rat was chosen as it has been shown to be a suitable model for this type of study and is the animal recommended in the test guideline.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
none used

MAXIMUM DOSE VOLUME APPLIED: 1.9 ml

DOSAGE PREPARATION (if unusual): The test item was administered, as supplied, at a volume of 1.9 ml/kg bodyweight (specific gravity 1.0484).

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 / sex / dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality: Cages of rats were checked at least twice daily for any mortalities.
Clinical signs: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1 (a period of approximately three hours). On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). This latter observation was at approximately 16.30 hours on week days or 11.30 hours on Saturdays and Sundays. The nature and severity of the clinical signs and time were recorded at each observation.
Bodyweight: The bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean bodyweights were calculated.
- Necropsy of survivors performed: yes
Macroscopic pathology: All animals were subjected to a macroscopic examination which consisted of opening the abdominal and thoracic cavities. The macroscopic appearance of all tissues was recorded.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths following a single oral dose of the test item to a group of ten rats (five males and five females) at a dosage of 2.0 g/kg bodyweight.

Clinical signs:

other: Piloerection was observed in all rats within ten minutes of dosing. This sign persisted and was accompanied in all animals on Day 2 only by soft to liquid faeces. There were no other clinical signs and recovery, as judged by external appearance and behavi

Gross pathology:

No macroscopic abnormalities were observed for animals killed on Day 15.

Interpretation of results:

GHS criteria not met

Remarks:

EU implementation

Conclusions:

The study was conducted under GLP according to OECD TG 401 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 acute oral toxicity in rats. The determined LD50 value is >2000 mg/kg bw, the LD0 ≥ 2000 mg/kg, as none of the animals died after gavage of 2000 mg/kg bw. The result is suitable to determine the classification of the test item. According to Regulation (EC) No. 1272/2008, the substance does not need to be classified as acute toxic cat. IV or higher.

Executive summary:

A study was performed to assess the acute oral toxicity of the test item to rats. The method followed was that described in OECD Guideline for Testing of Chemicals No. 401 "Acute Oral Toxicity", Adopted: 24 February 1987.

A group of ten fasted rats (five males and five females) was given a single dose by oral gavage of the test substance, as supplied, at a dose level of 2.0 g/kg bodyweight. All animals were killed and examined macroscopically on Day 15, the end of the observation period.

There were no deaths. Clinical signs of reaction to treatment were confined to piloerection and soft to liquid faeces, seen in ail rats. Recovery was complete in all instances by Day 3.

All rats achieved satisfactory bodyweight gains throughout the study.

No abnormalities were recorded at the macroscopic examination on Day 15.

The acute lethal oral dose to rats of Bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide was found to be greater than 2.0 g/kg bodyweight, the substance does not need to be classified as acute toxic cat. IV or higher according to Regulation (EC) No. 1272/2008.

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Remarks:

OECD 404

Reference

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

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

Specific details on test material used for the study:

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

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.

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.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: day 11

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

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: day 11

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.56

Max. score:

2

Reversibility:

fully reversible within: day 11

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

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

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

other: not applicable

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

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.

Cross-reference 3

Reason / purpose for cross-reference:

data waiving: supporting information

Remarks:

OECD 406

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1995-10-31 - 1995-12-03

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

OECD Guideline for Testing of Chemicals No. 406 "Skin Sensitisation". Adopted 17 July 1992.

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: MAGNUSSON, B. and KLIGMAN, A.M. (1970) Allergic Contact Dermatitis in the Guinea-pig: Identification of contact allergens, Thomas, C.C., Springfield, Illinois, U.S.A.

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study was conducted prior to the implementation of REACH and adoption of the LLNA or suitable in vitro methods.

Specific details on test material used for the study:

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

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, England.
- Age at study initiation: four to five weeks
- Weight at study initiation: 294 to 327 g on arrival
- Housing: The guinea-pigs were housed in groups of five in suspended metal cages with wire mesh floors.
- Diet (e.g. ad libitum): A vitamin C enriched guinea-pig diet FD2 was provided ad libitum. Hay was given weekly.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: All the guinea-pigs were acclimatised to the experimental environment for six days prior to allocation to the main study.
- Indication of any skin lesions: none stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Animal room temperature was maintained at approximately 21 °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 15 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.

Route:

intradermal

Vehicle:

other: Alembicol D

Concentration / amount:

0.1 ml of 0.5% solution

Day(s)/duration:

day 1

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

Route:

epicutaneous, occlusive

Vehicle:

unchanged (no vehicle)

Concentration / amount:

No. 3 paper was saturated with approximately 0.4 ml of 100% test item

Day(s)/duration:

six days after intradermal challenge for 48 h

Adequacy of induction:

highest technically applicable concentration used

No.:

#1

Route:

epicutaneous, semiocclusive

Vehicle:

other: Alembicol D

Concentration / amount:

Whatman No. 3 paper was saturated with approximately 0.2 ml of the test item as supplied and 50% v/v solution

Day(s)/duration:

two weeks after the topical induction for 24h

No. of animals per dose:

Six animals for the preliminary investigations, ten test and five control animals were used.

Details on study design:

RANGE FINDING TESTS:
Preliminary study
The intradermal and topical irritancy of a range of dilutions of the test substance was investigated to identify where possible (a) concentrations of the test substance that would produce irritation suitable for the induction phase of the main study and (b) a maximum non-irritant concentration by the topical route of administration for the challenge phase.
Animals for these investigations were pre-treated with an intradermal injection of Freund's complete adjuvant, 50:50 with water for irrigation (Ph. Eur), approximately two weeks prior to the start of the preliminary investigations.
Selection of concentrations of test substance for the main study: Based on the results of the preliminary investigations, the following concentrations of the test item were selected:
Induction intradermal injection - 0.5% v/v in Alembicol D (A product of coconut oil, supplied by Alembic Products, Saltney, Chester, England): This was the highest practical concentration that caused irritation but did not adversely affect the animals.
Induction topical application - as supplied
Topical challenge - as supplied and 50% v/v in Alembicol D
This was the highest practical concentration that could be dosed topically and did not give rise to irritating effects.

MAIN STUDY
A. INDUCTION EXPOSURE
Induction intradermal injections - test animals
A 40 x 60 mm area of dorsal skin on the scapular region of the guinea-pig was clipped free of hair with electric clippers. Three pairs of intradermal injections were made into a 20 x 40 mm area within the clipped area as shown in Figure 1.
Injectables for the test animals were prepared as follows:
1. Freund's complete adjuvant** was diluted with an equal volume of water for irrigation (Ph.Eur.).
2. Test item, 0.5% v/v in Alembicol D.
3.Test item, 0.5% v/v in a 50 : 50 mixture of Freund's complete adjuvant and Alembicol D.
** Difco Laboratories, Detroit 1, Michigan, U.S.A.
Induction topical application - test animals
The preliminary investigations indicated that the maximum practical concentration of the test substance for topical application (as supplied) did not produce skin irritation. Therefore, six days after the injections, the same 40 x 60 mm interscapular area was clipped and shaved free of hair and the site was pre-treated by gentle rubbing with 0.5 mJ per site of 10% w/w sodium lauryl sulphate in petrolatum. Twenty-four hours later a 20 x 40 mm patch of Whatman No. 3 paper was saturated with approximately 0.4 ml of the test item, as supplied. The patch was placed on the skin of the test animals and covered by a length of impermeable plastic adhesive tape (50 mm width "Blenderm"). This in turn was firmly secured by elastic adhesive bandage (50 mm width "Elastoplast") wound round the torso of the animal and fixed with "Sleek" impervious plastic adhesive tape. The dressing was left in place for 48 hours.
Induction - control animals
During the induction phase, the control animals were treated similarly to the test animals with the exception that the test substance was omitted from the intradermal injections and topical application.

B. CHALLENGE EXPOSURE
Challenge - control and test animals
The control and test animals were challenged topically two weeks after the topical induction application using the test item, as supplied and 50% v/v in Alembicol D.
Hair was removed by clipping and then shaving from an area on the left flank of each guinea-pig. A 20 x 20 mm patch of Whatman No. 3 paper was saturated with approximately 0.2 ml of the test item, as supplied and applied to an anterior site on the flank. The test item, 50% v/v in Alembicol D was applied in a similar manner to a posterior site. The patches were sealed to the flank for 24 hours under strips of "Blenderm" covered by "Elastoplast" wound round the trunk and secured with "Sleek".
Observations were made 24, 48, and 72 h after challenge

Challenge controls:

yes, animals not induced with the test item

Positive control substance(s):

yes

Remarks:

The sensitivity of the guinea-pig strain used is checked periodically at the laboratory with hexyl cinnamic aldehyde, a known sensitiser.

Positive control results:

In the available summary of 7 studies with the positive control, it induced the following positive responses (No. of animals with reactions / total number of animals): 10/10, 9/10, 10/10, 9/10, 10/10, 10/10, 8/10.
The positive control gave the appropriate results, and the used guinea pig strain showed the required sensitivity.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

undiluted & 50%

No. with + reactions:

0

Total no. in group:

10

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

undiluted

No. with + reactions:

5

Total no. in group:

10

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

50%

No. with + reactions:

0

Total no. in group:

10

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

undiluted

No. with + reactions:

6

Total no. in group:

10

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

50%

No. with + reactions:

1

Total no. in group:

10

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

undiluted & 50%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

only a few incidences of dryness and sloughing of the epidermis

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

undiluted & 50%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

only a few incidences of dryness and sloughing of the epidermis

Remarks on result:

no indication of skin sensitisation

Reading:

other: 3rd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

undiluted & 50%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

only a few incidences of dryness and sloughing of the epidermis

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

other: reading, No. not specified

Group:

positive control

Dose level:

induction: 10% intradermal, topical as supplied; challenge: as supplied and 50%

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Remarks:

Results in four studies; in 2 studies, 9/10 animals showed reacions, in one, 8/10 and 1 inconclusive result was revealed

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

The study was conducted under GLP according to OECD TG 406 (guinea pig maximisation test) on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies. Positive and negative controls gave the appropriate response. Hence, the results can be considered as sufficiently reliable to assess the irritating properties of the test item.
In this study, the test item produced evidence of skin sensitisation (delayed contact hypersensitivity) in five of the ten test animals. One animal gave an inconclusive response and the remaining four animals gave negative responses.
According to Regulation 1272/2008 / 286/2011, Table 3.4.4 Animal test results for sub-category 1B, a substance must be classified as skin sensitizer if in the Guinea pig maximisation test ≥ 30 % to < 60 % of the animals are responding at > 0.1 % to ≤ 1 % intradermal induction dose or ≥ 30 % responding at > 1 % intradermal induction dose. Intradermal induction was 0.5%, and 50% responded. Hence, Bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide must be regarded as skin sensitizer Cat. 1B.

Executive summary:

This study was performed to assess the skin sensitisation potential of Bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide using the guinea-pig. The method followed was that described in: OECD Guideline for Testing of Chemicals No. 406 "Skin Sensitisation". Adopted 17 July 1992, and MAGNUSSON, B. and KLIGMAN, A.M. (1970) Allergic Contact Dermatitis in the Guinea-pig: Identification of contact allergens, Thomas, C.C., Springfield, Illinois, U.S.A.

Based on the results of a preliminary study and in compliance with the guideline, the following dose levels were selected:

Intradermal injection: 0.5% v/v in Alembicol D

Topical application: as supplied v/v in Alembicol D

Challenge application: as supplied and 50% v/v in Alembicol D

Ten test and five control guinea-pigs were used in this study.

In this study Bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide produced evidence of skin sensitisation (delayed contact hypersensitivity) in five of the ten test animals. One animal gave an inconclusive response and the remaining four animals gave negative responses.

Bis(O,O-2-ethylhexyl-thiophosphoryl)polysulfide must be regarded as skin sensitizer Cat. 1B.