3-chloro-6-methyl-dibenzo[c,f][1,2]thiazepin-11(6H)-one 5,5-dioxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

The study was carried out based on the guidelines described in:
OECD, Section 4, Health Effects, No.429 (2010),
EC, No 440/2008; B42: "Skin Sensitization: Local Lymph Node Assay"
EPA, OPPTS 870.2600 (2003) “Skin Sensitization”.

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/J mice

Sex:

female

Study design: in vivo (non-LLNA)

No. of animals per dose:

5 females

Study design: in vivo (LLNA)

Vehicle:

propylene glycol

No. of animals per dose:

20 females (5 females per group)
Group 1: 0% w/w
Group 2: 10% w/w
Group 3: 25% w/w
Group 4: 50% w/w

Results and discussion

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

ca. 1.3

Test group / Remarks:

10%

Results 2

Key result

Parameter:

SI

Value:

ca. 1.4

Test group / Remarks:

25%

Results 3

Key result

Parameter:

SI

Value:

>= 1.5 - <= 3.1

Test group / Remarks:

50%

Any other information on results incl. tables

Skin reactions / Irritation

No irritation of the ears was observed in any of the animals examined.

Systemic toxicity (Body weights

No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. The body weight loss noted for a few animals was considered not toxicologically significant since the changes were slight in nature and no concentration-related incidence was apparent.

Macroscopy of the auricular lymph nodes and surrounding area

The majority of auricular lymph nodes were considered normal in size, except for both nodes in two animals at a 50% test substance concentration (nos. 18 and 19) which appeared larger in size when compared to the other treated groups. No macroscopic abnormalities of the surrounding area were noted in any of the animals.

Radioactivity measurements

Mean DPM/animal values for the experimental groups treated with test substance concentrations 10 and 25% were 428 and 472 DPM respectively. The mean DPM/animal value at a 50% test substance concentration was 507 DPM (when one high value was excluded) or 1049 (without exclusion of the high value). The mean DPM/animal value for the vehicle control group was 341 DPM.

The DPM value for one animal at a 50% concentration (no. 18) was determined to be an outlier at a significance level of 0.05 but not at p 0.01.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The SI values calculated for the substance concentrations 10 and 25% were 1.3 and 1.4, respectively. The SI value calculated for the 50% test substance concentration was 1.5 (when one high value was excluded) or 3.1 (without exclusion of the high value). Upon excluding the high DPM value of one animal at 50%, the mean SI over the dose groups did not show a meaningful increase (1.3 at 10% to 1.5 at 50%). The Grubb’s outlier test showed that this value was an outlier (at p 0.05 but not at p 0.01). Also, 3 out of 5 DPM values at a 50% test substance concentration were essentially within the DPM range encountered over the other dose groups.
Based on these results it was considered that there was no indication that the test substance elicits an SI ≥ 3 when tested up to 50%. 1574 CETONA was therefore considered not to be a skin sensitizer, and it was established that the EC3 value (the estimated test substance concentration that will give a SI =3) (if any) exceeds 50%.
The six-month reliability check with Alpha-hexylcinnamicaldehyde indicates that the Local Lymph Node Assay as performed at WIL Research Europe is an appropriate model for testing for contact hypersensitivity.
Based on these results, 1574 CETONA would not be regarded as a skin sensitizer according to the recommendations made in the test guidelines. The test substance does not have to be classified and has no obligatory labelling requirement for sensitization by skin contact according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) and the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.