Reaction product of Propanoic acid, 3-[[bis(2-methylpropoxy)phosphinothioyl]thio]-2-methyl- and tridecanamine, N-tridecyl-, branched and linear

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-08-04 to 2014-09-23

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

April 24, 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

May 30, 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

August 1998

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japan MAFF Testing Guideline of 12 Nousan No. 8147; November 24, 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bioassay-Labor für biologische Analytik GmbH, Im Neuenheimer Feld 515-519, 69120 Heidelberg, Germany

Test material

Test material information

1

Reference substance name:

Reaction product of Propanoic acid, 3-[[bis(2-methylpropoxy)phosphinothioyl]thio]-2-methyl- and tridecanamine, N-tridecyl-, branched and linear

EC Number:

944-290-5

Molecular formula:

C38H80NO4PS2 (idealized)

IUPAC Name:

Reaction product of Propanoic acid, 3-[[bis(2-methylpropoxy)phosphinothioyl]thio]-2-methyl- and tridecanamine, N-tridecyl-, branched and linear

Test material form:

liquid: viscous

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories, Netherlands
- Age at study initiation: Approx. 5-8 months
- Weight at study initiation: 3.49 kg – 4.35 kg
- Housing: individually
- Diet: ad libitum (STANRAB (P) SQC; SDS Special Diets Services, 67122 Altrip, Germany)
- Water: tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated skin served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: flank (2.5 chm x 2.5 cm)
- Type of wrap if used: Fixomull® stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing: with Lutrol® (Polyethylene glycol) and Lutrol® / water (1 : 1)
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to mentioned system in the quoted guidelines

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 eschar formation preventing grading of erythema

Edema formation
0 No edema
1 Very slight edema (barely perceptible)
2 Slight edema (edges of area well- defined by definite raising)
3 Moderate edema (raised approx. 1 mm)
4 Severe edema (raised more than 1 mm and extending beyond area of exposure)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48, 72 hours

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48, 72 hours

Score:

3.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48, 72 hours

Score:

3.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48, 72 hours

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48, 72 hours

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48, 72 hours

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritant / corrosive response data:

The first animal revealed well-defined erythema (grade 2) immediately after removal of the patch until hour 1 after removal of the patch which increased to moderate erythema (grade 3) from hour 24 until hour 72. From study day 7 until day 14, severe erythema (grade 4) was seen in this animal.
Very slight edema (grade 1) was noted at hour 1 after removal of the patch in the first animal and increased to slight edema (grade 2) at hour 24. From hour 48 until hour 72, moderate edema (grade 3) was seen and increased to severe edema (grade 4) on day 7. Finally, slight edema (grade 2) was noted on day 14.
Erythema and edema were observed beyond the application area from hour 48 until day 14. On day 7 only, a yellowish discoloration was seen on the application area. In addition, strong scaling formation and plaque-like incrustations were seen on day 14.
The second animal revealed very slight erythema (grade 1) immediately after removal of the patch. At hour 1 after removal of the patch the finding increased to well-defined erythema (grade 2). Moderate erythema (grade 3) was noted from hour 24 until hour 48. From hour 72 until study day 7, severe erythema (grade 4) was seen in this animal, which regressed to moderate erythema on day 14.
Very slight edema (grade 1) was noted at hour 24 after removal of the patch and increased to slight edema (grade 2) at hour 48. From hour 72 until day 7, severe edema (grade 4) was seen in this animal while moderate edema (grade 3) was noted on day 14.
Erythema beyond the application area was observed from hour 1 until day 14. Additionally, edema beyond the application area was observed from hour 48 until day 14. On day 7 only, yellowish to brownish discoloration was seen on the application area. In addition, scaling was noted on day 7 and 14.
The third animal revealed well-defined erythema (grade 2) immediately after removal of the patch. This finding increased to moderate erythema (grade 3) from hour 1 until hour 48. From hour 72 until day 7, severe erythema (grade 4) was seen in this animal, which decreased to moderate erythema on day 14.
Very slight edema (grade 1) was noted immediately after removal of the patch until hour 1 after removal of the patch and increased to slight edema (grade 2) at hour 24 and 48. At hour 72 moderate edema (grade 3) was seen and increased to severe edema (grade 4) on day 7. Thereafter, moderate edema (grade 3) was noted on day 14 again.
Erythema and edema were observed beyond the application area from hour 24 until day 14. Additionally, scaling was seen on day 14.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The substance is irritating to rabbit skin (OECD 404, GLP).