N,N-dimethyl-p-toluidine

Endpoint summary

Description of key information

Patch test was performed to evaluate the sensitization potential of the test chemical when used in dental materials. A 79 year old female experienced severew burning of her tongue and soreness for more than a year, starting from few months she started wearing her new dentures.Patch test was performed with European standard series including scrapings of the patients dentures and a dental material series to ascertain the causative agent. The reactions were observed and scored on day 2,3 after patch removal.The patient showed 2+ reaction on day 2,3 to 5% test chemical in petrolatum. hence. the test chemical can be considered to be sensitizing to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from peer reviewed journals

Qualifier:

according to guideline

Guideline:

other: Patch test

Principles of method if other than guideline:

Patch test was performed to evaluate the sensitization potential of the test chemical when used in dental materials

GLP compliance:

not specified

Type of study:

patch test

Justification for non-LLNA method:

No data available

Species:

other: humans

Strain:

not specified

Sex:

female

Details on test animals and environmental conditions:

Source: Department of Dermatology, Free University Academic Hospital, Amsterdam.
Age: 79 years old

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

5% in petrolatum

Adequacy of induction:

not specified

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

5% in petrolatum

Adequacy of challenge:

not specified

No. of animals per dose:

1

Details on study design:

Patch test with European standard series including scrapings of the patients dentures and a dental material series were conducted. The reactions were observed and scored on day 2,3 after patch removal.

Positive control substance(s):

not specified

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5% in petrolatum

No. with + reactions:

1

Total no. in group:

1

Clinical observations:

The patient showed 2+ reaction on day 2,3 to 5% test chemical in petrolatum

Remarks on result:

positive indication of skin sensitisation

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

The patient showed 2+ reaction on day 2,3 to 5% test chemical in petrolatum. Hence, the test chemical can be considered to be sensitizing to skin.

Executive summary:

Patch test was performed to evaluate the sensitization potential of the test chemical when used in dental materials. A 79 year old female experienced severew burning of her tongue and soreness for more than a year, starting from few months she started wearing her new dentures.Patch test was performed with European standard series including scrapings of the patients dentures and a dental material series to ascertain the causative agent. The reactions were observed and scored on day 2,3 after patch removal.The patient showed 2+ reaction on day 2,3 to 5% test chemical in petrolatum. Hence, the test chemical can be considered to be sensitizing to skin.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Various studies have been investigated for assessing the dermal sensitization potential of the test chemical to a greater or lesser extent. The studies include human data for the test chemical.

Patch test was performed to evaluate the sensitization potential of the test chemical when used in dental materials. A 79 year old female experienced severew burning of her tongue and soreness for more than a year, starting from few months she started wearing her new dentures. Patch test was performed with European standard series including scrapings of the patients dentures and a dental material series to ascertain the causative agent. The reactions were observed and scored on day 2,3 after patch removal. The patient showed 2+ reaction on day 2,3 to 5% test chemical in petrolatum. hence. the test chemical can be considered to be sensitizing to skin.

This is supported by another patch test conducted for screening of contact allergens from dental implants. A 62 year old female complained of burning and soreness of the mouth from one month. On close examination, diffuse redness and hard palate was observed. She had recently started using a dental prothesis, which while using the symptoms were noted. The patient was patch tested with GIRDCA series which were negative. So the patient was further with dental material series using petrolatum as vehicle. The patient showed strong reactions[++] to the test chemical [1% in petrolatum] at 48 and 72 hours readings. The patient was adviced to stop using the dental prothesis, after which she showed signs of recovery.Based on the above findings, the test chemical can be considered to be sensitizing to skin.

The above results are supported by Epicutaneous patch tests performed with denture materials to obtain further information regarding the sensitivity caused by them in humans. The materials consisted of denture wearing persons from Department of Prosthetic Densistry and Department of Dermatology during the years 1970 -76. The test group consisted of seven men and 46 women with a mean age of 61 and 67 respectively. The symptoms corresponding to the component of the denture materials were recorded and identified. 39 patients wore a complete lower and upper denture, while the remaining wore a partial denture with a cast metal framework.

Patch tests were performed on the skin of the back of the patients according to ICDRG Guidelines. Readings were performed after 48 and 72 hours. A positive reaction was indicated by erythema and infiltration without (+) or with papules or vesicles (++).Concentrations of the test chemical were evaluated as non-toxic after testing on 20 normal individuals. Positive skin reactions were observed in 15/53 patients tested with 30% test chemical in olive oil at 48 and 72 hours. Hence the test chemical can be considered to be sensitizing to skin.

These results are also supported by a study where 791 patients were tested with denture mateirals recommended by German Contact Dermatitis Group and IVDK. Patch tests were performed in accordance with the procedures accepted by ICDRG AND DKG. 2% test chemical in petrolatum was applied in Finn Chambers on Scanpor tape to the skin of 725 patients. Patch test application time was 2 days. Readings were taken in duplicates until at least day 3. A test reaction was rated as positive in the case of erythema, infiltration and papules[+], additional vesciles [++] or additional confluent vesciles [+++]. Statistical analysis was done using SAS systems. Questionable positive reactions were observed in 10/725 patients and + reaction [erythema, infiltration and papules] was observed in 1/725. The overall % of positive reactions was 0.1%.

Based on the above findings, it can be concluded that the test chemical has the potential to cause sensitization to skin.

These results are further supported by a Patch test performed to evaluate the causative components causing Allergic Contact Dermatitis from Two-component Acrylic Resin used by manicurist. A 35-year-old female noticed itching at the tips of her fingers when touching artificial nail materials three months after she started to use them. She complained of severe itchy eczema around her nails and onycholysis one year later. She was patch tested with the four kinds of products[liquid monomers, primers, accelators, removers] using petrolatum as vehicle. Readings were performed 1 day and 5 days after occlusion for 2 days (day 3 and day 7) according to the International Contact Dermatitis Research Group (ICDRG) standard.The symptoms disappeared under treatment with topical corticosteroid, but numbness at the tips of her fingers continued for the next month. She experienced recurrence of her symptoms after she used the same artificial nail materials again on one of her customers; therefore, she gave up using those substances. Apart from the positive reactions observed for the liquid monomers, primers, accelarators, a (+) reaction was noted in the patient when tested with 2% test chemical in petrolatum on day 7.Hence, the test chemical can be considered to be sensitizing to skin.

These results are also supported by another patch testing performed with a standard routine series and a standardized denture-dental (acrylate and metal) series to evaluate the possible role of local hypersensitivity reactions to denture or dental components as etiologic factors in Burning Mouth Syndrome. In 22 patients (19 women, 3 men, mean age 56 years) classified with BMS, clinical and laboratory investigations were performed, with particular emphasis on the role of contact hypersensitivity. Twenty of the 22 patients wore a complete or partial denture. Patch tests were performed on the back with a standardized method with the routine series (ICDRG series) suppIemented with an acrylate series, a dental metal series, and a spices series.Dental metal allergens were used in concentrations as indicated in the literature. Standardized allergens from the acrylate series were obtained commercially (Chemotechnique Diagnostics). Spices were tested as indicated previously. 24 Fifty control subjects tested were negative to the allergens of the spices series. 24 Material obtained by scraping the patients' dentures or dental inlays was tested if possible. Denture cleaning products were also tested. Positive reactions were seen in 3 of 22 patients tested with the test chemical.Hence, the test  chemical can be considered to be sensitizing to skin.

Based on the available patch test results, the test chemical can be considered to have a potential to cause sensitization to skin. Hence, the test chemical was considered to be skin sensitizer and classified under the category “Category 1” as per CLP Regulation.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available patch test results, the test chemical can be considered to have a potential to cause sensitization to skin. Hence, the test chemical was considered to be skin sensitizer and classified under the category “Category 1” as per CLP Regulation.