Dibutyl [[bis[(2-ethylhexyl)oxy]phosphinothioyl]thio]succinate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

19 December 2017 to 5 September 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, 12 NouSan No. 8147, 24 November 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Dibutyl [[bis[(2-ethylhexyl)oxy]phosphinothioyl]thio]succinate

EC Number:

270-220-1

EC Name:

Dibutyl [[bis[(2-ethylhexyl)oxy]phosphinothioyl]thio]succinate

Cas Number:

68413-48-9

Molecular formula:

C28H55O6PS2

IUPAC Name:

1,4-dibutyl 2-({bis[(2-ethylhexyl)oxy](sulfanylidene)-λ⁵-phosphanyl}sulfanyl)butanedioate

Test material form:

liquid

Specific details on test material used for the study:

- Purity: 84%
- Physical State/Appearance: Clear colourless liquid

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/Ca (CBA/CaOlaHsd)

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS B.V., Inc., Horst, The Netherlands
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: Ranged from 15 to 23 g
- Housing: Suspended solid floor polypropylene cages with stainless steel mesh lids
- Diet: 2014C (Teklad Global Certified Rodent diet), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): at least fifteen
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

25, 50, 100 (%v/v) in acetone/olive oil 4:1

No. of animals per dose:

Five

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

α-Hexylcinnamaldehyde, tech., 85% was considered to be a sensitizer under the conditions of the test.

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

2.1

Test group / Remarks:

25 (%v/v) in acetone/olive oil 4:1

Results 2

Key result

Parameter:

SI

Value:

2.99

Test group / Remarks:

50 (%v/v) in acetone/olive oil 4:1

Results 3

Key result

Parameter:

SI

Value:

7.38

Test group / Remarks:

100 (%v/v) in acetone/olive oil 4:1

Any other information on results incl. tables

Table 1: Stimulation Index of the Test Item

Concentration (%v/v) in acetone/olive oil 4:1	Stimulation Index	Result
25	2.10	Negative
50	2.99	Negative
100	7.38	Positive

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

The test item with approximately 0.5% (w/w) dibutyl fumarate impurities is classified as a contact sensitizer (Category 1B), according to GHS.

Executive summary:

The study was performed to the standardised guidelines OECD 429, under GLP conditions. Three groups, each of five CBA/Ca mice were treated with 50 µL (25 µL per ear) of the undiluted test item or the test item as a solution in acetone/olive oil 4:1at concentrations of 50% or 25% v/v. A further group of five animals was treated with the vehicle alone in the same manner.

 

The concentration of the test item expected to cause a 3 fold increase in 3HTdR incorporation (EC3 value) was calculated to be 50.1%. The test item, which contains approximately 0.5% (w/w) dibutyl fumarate, a known sensitizer, was considered to be a weak skin sensitizer with an EC3 of 50.1% under the conditions of the test, however, the test item is classified as a contact sensitizer (Category 1B) according to GHS.