Phosphorodithioic acid, O,O-bis(2-methylpropyl) ester, compd. with N,N-dimethylmethanamine (1:1)

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 June - 9 August 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Also in accordance with GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

O,O-bis(2-methylpropyl) sulfanidylphosphonothioate; trimethylazanium

EC Number:

700-910-4

Cas Number:

1354201-99-2

Molecular formula:

C11H28NO2PS2

IUPAC Name:

O,O-bis(2-methylpropyl) sulfanidylphosphonothioate; trimethylazanium

Test material form:

solid

Remarks:

pale yellow glassy solid

Specific details on test material used for the study:

- Name of test material (as cited in study report): S-10713
- Physical state: solid
- Colour: brown
- Storage condition of test material: at room temperature in the dark
- Lot/batch No.: S20227-179

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Leicestershire, UK
- Age at study initiation: 12-20 weeks
- Weight at study initiation: 2.35-2.78 kg
- Housing: individually in suspended cages
- Diet: free access to 2930 Teklad Global Certified Rabbit diet (Harlan Laboratories UK Ltd., Oxon, UK)
- Water: free access to mains drinking water
- Acclimation period: at least 5 days

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

IN-LIFE DATES: 28 June - 9 August 2011

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

moistened with 0.5 ml distilled water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours (first rabbit)
4 hours (two subsequent rabbits)

Observation period:

14 days

Number of animals:

3

Details on study design:

COVERAGE
At three sites on the back of one rabbit the test substance was introduced under a 2.5 x 2.5 cm cotton gauze patch secured with surgical adhesive tape and the trunk was wrapped in an elasticated corset. Two additional rabbits were only exposed at one site for 4 hours.

REMOVAL
Any residual test substance was removed with cotton wool soaked in distilled water.

SCORING SYSTEM
According to OECD 404.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.66

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: slight desquamation at day 7

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: desquamation at day 7

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: dermal haemorrhage in centre of test site (approx. 8x12 mm) till 72 hours; slight desquamation or hardened dark brown/black colour scab at day 7

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

Very slight erythema was noted immediatly after patch removal after 3-minute exposure (1/24/48/72h score 0 for erythema and edema).
There was no evidence of skin irritation after 1 hour exposure (all scores 0).

After 4-h exposure very slight or well-defined erythema and very slight to moderate oedema were noted at two treated skin sites immediately and one hour after patch removal. Well-defined erythema and very slight or slight oedema were noted at all treated skin sites at the 24 and 48-h observations. Well-defined erythema and very slight or slight oedema were noted at two treated skin sites with very slight erythema and very slight oedema noted at the remaining treated skin site at the 72-h observation.

An area of dermal haemorrhage, approximately 8x12 mm in size, was noted in the centre of one treated skin site one hour after patch removal and at the 24, 48 and 72-h observations with a hardened dark brown/black coloured scab, which prevented accurate evaluation of erythema and oedema, noted at the 7-day observation. This treated skin site appeared normal at the 14-day observation. Slight desquamation was noted at two treated skin sites at the 7-day observation.

Other effects:

All animals showed expected gain in body weight during the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The substance is slighlty irritating, but not sufficient for classification according to EC Regulation 1272/2008.

Executive summary:

In a skin irritation study performed according to OECD 404 and EC 440/2008 B4 and following GLP principles, rabbits were exposed to the test substance for 3 min, 1h and 4h under semi-occlusive condtions.

No signs of skin irritation were noted after 3 min and 1h of exposure (Erythema and Edema scores at time points 24, 48 and 72h were all 0).

After 4-h exposure very slight or well-defined erythema and very slight to moderate oedema were noted at two treated skin sites immediately and one hour after patch removal. Well-defined erythema and very slight or slight oedema were noted at all treated skin sites at the 24 and 48-h observations. Well-defined erythema and very slight or slight oedema were noted at two treated skin sites with very slight erythema and very slight oedema noted at the remaining treated skin site at the 72-h observation.

An area of dermal haemorrhage, approximately 8x12 mm in size, was noted in the centre of one treated skin site one hour after patch removal and at the 24, 48 and 72-h observations with a hardened dark brown/black coloured scab, which prevented accurate evaluation of erythema and oedema, noted at the 7-day observation. This treated skin site appeared normal at the 14-day observation. Slight desquamation was noted at two treated skin sites at the 7-day observation.

Based on the results, the test material is not considered as irritating to skin and no classification is required.