Ethyl [(4-methylphenyl)sulphonyl]carbamate

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:

other: GLP. Guideline study

Data source

Reference

Reference Type:

other: Body responsible for the test

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

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:

Ethyl [(4-methylphenyl)sulphonyl]carbamate

EC Number:

226-952-9

EC Name:

Ethyl [(4-methylphenyl)sulphonyl]carbamate

Cas Number:

5577-13-9

Molecular formula:

C10H13NO4S

IUPAC Name:

ethyl [(4-methylphenyl)sulfonyl]carbamate

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/J mice

Sex:

female

Study design: in vivo (LLNA)

No. of animals per dose:

20 females (5 females per group)
Group 1: 0% w/w
Group 2: 20% w/w
Group 3: 40% w/w
Group 4: 80% w/w

Results and discussion

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

other: Number of micronucleated polychromatic erythrocytes per 2000 polychromatic erythrocytes

Variability:

Range 0-5

Test group / Remarks:

Male

Remarks on result:

other: Number of micronucleated polychromatic erythrocytes per 2000 polychromatic erythrocytes was determined see explanation below

Remarks:

Number of micronucleated polychromatic erythrocytes per 2000 polychromatic erythrocytes males Range 0 - 5 Mean 1.2 SD 1.2 n 180 SD = Standard deviation n = Number of observations Since there were no substantial differences between sexes in toxicity only male animals were used in the main study. Five male animals were used in each treatment group. The mean number of micronucleated polychromatic erythrocytes scored in Tolfamato treated groups were compared with the corresponding vehicle control group. All animals treated with Tolfamato exhibited both group mean and individual micronucleated polychromatic erythrocytes frequencies which were comparable with both the concurrent vehicle control and the laboratory’s historical vehicle control data for both time points. The groups that were treated with Tolfamato showed no decrease in the ratio of polychromatic to normochromatic erythrocytes compared to the concurrent vehicle control group, indicating a lack of toxic effects of this test substance on erythropoiesis. The groups that were treated with cyclophosphamide showed an expected decrease in the ratio of polychromatic to normochromatic erythrocytes compared to the vehicle controls, demonstrating toxic effects on erythropoiesis.

Results 2

Key result

Parameter:

other: Mortality and toxic signs

Remarks on result:

other: Mortality and toxic signs was observed. See explanation below

Remarks:

The animals of the group treated with 375 mg Tolfamato/kg body weight and the animals of the negative and positive control groups showed no treatment related clinical signs of toxicity or mortality. The following clinical observations were made in the groups treated with 1500 and 750 mg Tolfamato/kg body weight: During the first hour after dosing 4 animals of the groups treated with 1500 mg/kg body weight were lethargic, 3 of them also showed ataxia and the fourth animal also showed ventral recumbency. All other animals treated with 1500 mg/kg body weight and the animals treated with 750 mg/kg body weight showed no reaction to treatment. Within 2 hours after dosing 6 animals of the groups treated with 1500 mg/kg body weight and 1 animal treated with 750 mg/kg body weight showed the following toxic signs: lethargy, rough coat and hunched posture. One animal treated with 1500 mg/kg body weight had a rough coat. Within 19 hours after dosing all animals had recovered from the treatment except for one animal treated with 1500 mg/kg body weight which still showed the following toxic signs: lethargy, rough coat and hunched posture. The animal recovered from the treatment within 43 hours after dosing.

Any other information on results incl. tables

Skin reactions/irritation: no irritaion of the ears was observed in any of the animals examined.

Systemic toxicity: body weights and body weight gains of experimental animals remained in the same range as controls over the study period. The body weight loss noted for some animales across the dose gropus 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: All auricular lymph nodes were normal in size and no macroscopic abnormalities of the surrounding area were noted in any of the animals.

Readioactivity measurements: Mean DPM/animal values for the experimental groups treated with test substance concentrations 20, 40 and 80% were 323,253 and 305 DPM respectively. The mean DPM/animal value for the vehicle control group was 437 DPM.

Applicant's summary and conclusion

Interpretation of results:

other: Not induce delayed contact hypersensivity in the murine LLNA. For more information, see Executive summary.

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Tolfamato would not be regarded as a skin sensitizer according to the recommendations made in the test guidelines. The test substance does not has to be classified and has no obligatory labelling requirement for sensitization by skin contact.

Executive summary:

Interpretation of results:

Not induce delayed contact hypersensivity in the murine LLNA. Mean DPM/animal values for the experimental grous treated with test substance concentration 20, 40 an 80% were 323, 253 and 305 DPM respectively. The mean DPM/animal value for the vehicule control group was 437 DPM.

The SI values calculated for the substance concentrations 20, 40 an 80% were 0.7, 0.6 and 0.7 respectively.

Since there was no indication that the test substance elicits an SI >= 3 when teste up to 80%. TOLFAMATO was considered not to be a skin sensitizer. It was established that the EC3 value (the estimated test substance concentration that will give a SI=3) (If any) exceeds 80%.