sodium;2-hexadecylsulfanyl-1H-benzimidazole-5-sulfonate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2004

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2002

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Draft 2001

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

2003

GLP compliance:

yes

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

sodium;2-hexadecylsulfanyl-1H-benzimidazole-5-sulfonate

EC Number:

616-081-6

Cas Number:

743423-33-8

Molecular formula:

C23 H37 N2 Na O3 S2

IUPAC Name:

sodium;2-hexadecylsulfanyl-1H-benzimidazole-5-sulfonate

impurity 1

Reference substance name:

1-hexadecyl-2-hexadecylsulfanyl-benzimidazole-5-sulfonate sodium salt

Molecular formula:

C39 H69 N2 Na O3 S2

IUPAC Name:

1-hexadecyl-2-hexadecylsulfanyl-benzimidazole-5-sulfonate sodium salt

impurity 2

Reference substance name:

N,N-dimethylacetamide

EC Number:

204-826-4

EC Name:

N,N-dimethylacetamide

Cas Number:

127-19-5

Molecular formula:

C4H9NO

IUPAC Name:

N,N-dimethylacetamide

impurity 3

Reference substance name:

Ethyldiisopropylamine

EC Number:

230-392-0

EC Name:

Ethyldiisopropylamine

Cas Number:

7087-68-5

Molecular formula:

C8H19N

IUPAC Name:

N-ethyl-N-isopropylpropan-2-amine

Test material form:

solid: particulate/powder

Remarks:

off-white powder with lumps

Details on test material:

Traces of 1-bromohexadecane

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

Age and bodyweight: Young adult animals (approx. 10 weeks old) were selected. Body weight variation was within +/- 20% of the sex mean.
Identification: Tail mark.

Conditions
Animals were housed in a controlled environment, in which optimal conditions were considered to be approximately 15 air changes per hour, a temperature of 21.0 +- 3.0°C (actual range: 19.1 - 21 .7°C), a relative humidity of 30-70% (actual range: 32 — 88%) and 12 hours artificial fluorescent light and 12 hours darkness per day.
Cleaning procedures in the room might have caused the temporary fluctuations above the optimal maximum level of 70% for relative humidity. Based on laboratory historical data, these fluctuations were considered not to have affected the study integrity.

Accommodation
Individual housing in labelled Macrolon cages (type l; height 12.5 cm) containing purified sawdust as bedding material (Woody-Clean type 3/4; Tecnilab-BMI BV, Someren , The Netherlands). Certificates of analysis were examined and then retained in the NOTOX archives.
The acclimatisation period was at least 5 days before the start of treatment under laboratory conditions. Animals were group housed in polycarbonate cages (Macrolon II type; height 15 cm) during the acclimatisation period.

Diet
Free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Lage, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.

Water
Free access to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.
Results of analysis for ingredients and/or contaminants of diet, sawdust, and water were assessed and did not reveal any findings that were considered to have affected study integrity.

Study design: in vivo (LLNA)

Vehicle:

methyl ethyl ketone

Remarks:

Vehicle was selected based on trial formulations performed at NOTOX

Concentration:

Vehicle control, 5%, 25% and 50% of test substance concentration

No. of animals per dose:

5

Details on study design:

Three groups of five animals were treated with three test substance concentrations respectively. One group of five animals was treated with vehicle.

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Value:

1

Variability:

SD = 0

Test group / Remarks:

Vehicle control

Results 2

Parameter:

SI

Value:

1

Variability:

SD = 0.7

Test group / Remarks:

5% test substance

Results 3

Parameter:

SI

Value:

1.3

Variability:

SD = 1.0

Test group / Remarks:

25% test substance

Results 4

Parameter:

SI

Value:

0.6

Variability:

SD = 0.7

Test group / Remarks:

50% test substance

Cellular proliferation data / Observations:

Induction phase
No irritation was observed in any of the animals examined.

Macroscopy
The majority of nodes were equal in size. No other macroscopic abnormalities of the nodes were noted.

Body Weights
Body weights and body weight gain of experimental animals remained in the same range as controls over the study period. The slight body weight loss, noted in some animals, was considered not toxicologically significant.

Radioactivity Measurements
Mean DPM/animal values for the experimental groups treated with test substance concentrations 5, 25 and 50% were 316, 395 and 196 respectively. The mean DPM/animal value for the vehicle control group was 311.

Toxicity I Mortality
No mortality occurred and no symptoms of systemic toxicity were observed in the animals of the main study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The SI values calculated for the substance concentrations 5, 25 and 50% were 1.0, 1.3 and 0.6 respectively. There was no indication that the test substance could elicit an SI >= 3.
Based on these results and according to the recommendations made in the test guidelines (OECD No.429, EC B.42 and EPA OPPTS 870.2600), V182675 should not be regarded as a skin sensitiser.

Based on these results and according to the:
- OECD Harmonized Integrated Hazard Classification System for Human Health and Environmental Effects of Chemical Substances (OECD, 1998), V182675 does not have to be classified for sensitisation by skin contact.
- EC criteria for classification and labelling requirements for dangerous substances and preparations (Council Directive 67/548/EEC), V182675 does not have to be classified and has no obligatory labelling requirement for sensitisation by skin contact.