3-chloro-2-[3-(chloroacetyl)-4,5-dihydro-1,2-oxazol-5-yl]phenyl methanesulfonate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 Aug - 29 Sep 2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The study followed the standard guideline of reference (OECD 429), which describes a procedure designed to evaluate the skin sensitisation hazard, but with an important protocol deviation. Cellular proliferation was not determined by incorporated radioactivity, thus no disintegrations per minute (DPM) were reported. Instead, lymph node weight and lymph node cell count were used as direct measurement of cell proliferation. Stimulation indices were calculated by dividing the average absolute lymph node weight or lymph node cell counts per group of the test item treated animals by those of the vehicle control animals. Thus, a lower cut-off value of 1.4 times increase of stimulation index was used. The results were reviewed for reliability and assessed as valid, and the study was conducted under GLP condition.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted in 2010

Deviations:

yes

Remarks:

Proliferation was assessed on Day 4 instead of Day 6 and determined by lymph node cell count instead of incorporated radioactivity, no Draize scoring of skin reactions

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted in 2012

GLP compliance:

yes (incl. QA statement)

Remarks:

Behörde für Gesundheit und Verbraucherschutz, Hamburg, Germany

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

3-chloro-2-[3-(2-chloroacetyl)-4,5-dihydro-1,2-oxazol-5-yl]phenyl methanesulfonate

EC Number:

811-477-7

Cas Number:

1446134-16-2

Molecular formula:

C12H11Cl2NO5S

IUPAC Name:

3-chloro-2-[3-(2-chloroacetyl)-4,5-dihydro-1,2-oxazol-5-yl]phenyl methanesulfonate

In vivo test system

Test animals

Species:

mouse

Strain:

NMRI

Remarks:

Crl:NMRI

Sex:

female

Study design: in vivo (LLNA)

Vehicle:

dimethylformamide

Concentration:

2, 10 and 50% (w/w)

No. of animals per dose:

6 females

Positive control substance(s):

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

Results and discussion

Positive control results:

The positive control substance alpha-hexyl cinnamic aldehyde (20% in acetone:olive oil (4:1 v/v), 25 µL/ear) was considered to be a sensitiser under the conditions of the test. A stimulation index of 1.549 was obtained (vehicle of the positive control: stimulation index of 1.0).

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

3.406

Test group / Remarks:

2%

Remarks on result:

other: SI = Cell count of treated group / Cell count of control group

Results 2

Key result

Parameter:

SI

Value:

3.757

Test group / Remarks:

10%

Remarks on result:

other: SI = Cell count of treated group / Cell count of control group

Results 3

Key result

Parameter:

SI

Value:

3.438

Test group / Remarks:

50%

Remarks on result:

other: SI = Cell count of treated group / Cell count of control group

Applicant's summary and conclusion

Interpretation of results:

other: Skin sens. 1B, H317 according to Regulation (EC) No. 1272/2008.

Conclusions:

The test substance at concentrations of ≥ 2% (w/w) showed skin sensitising properties in this modified local lymph node assay in mice. Thus, classification as Skin sens 1B (H317) is required according to Regulation (EC) No. 1272/2008.