Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: acceptabel well-documented publication, which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Identification of causative chemicals of allergic contact dermatitis using a combination of patch testing in patients and chemical analysis - Application to cases from rubber gloves
Author:
Kaniwa, M.A., K. Isama, A. Nakamura, H. Kantoh, K. Hosono, M. Itoh, K. Shibata, T. Usuda, K. Asahi, T. Osada, K. Matsunaga and H. Ueda
Year:
1994
Bibliographic source:
Contact Dermatitis, 1994, 31, 65-71

Materials and methods

Principles of method if other than guideline:
Investigation of 5 cases of allergic contact dermatitis from rubber gloves using patch testing and chemical analysis of causative rubber products by GC and HPLC.
GLP compliance:
not specified
Type of study:
patch test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
DMA obtained from Tokyo Kasei (Japan)
tested via HPLC showed only a single peak, so the substances were used without further purification
DMA solved in white petrolatum at a concentration of 1 %.

In vivo test system

Test animals

Species:
human
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
human 31 years, male
human, 49 years, male
human, 51 years, female
human, 38 years, male
human, 31 years, female

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: happened in the past, after wearing gloves
Vehicle:
petrolatum
Remarks:
white petrolatum
Concentration / amount:
concentration 1 %, or 2 % in white petrolatum respectivly.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Remarks:
white petrolatum
Concentration / amount:
concentration 1 %, or 2 % in white petrolatum respectivly.
No. of animals per dose:
no applicable
Positive control substance(s):
not required

Results and discussion

Any other information on results incl. tables

Case 1: reacted to TMTD-ZDMC as a group (glvoes A, but DMA was also detected in the chemical anaylsis of gloves A)

Case 2: reacted to TMTD-TMTM-ZDMC as a group (gloves C)

Case 3: reacted to TMTD-TMTM-ZDMC-DMA as a group (gloves E)

Case 4: no data refering to DMA or ZDMC (gloves C)

Case 5: reacted to TMTD-TMTM-ZDMC-DMA as a group

DMA was in gloves A and C detectable via GC or HPLC.

Applicant's summary and conclusion

Conclusions:
DMA is a substance which can challenge an allergic dermatitis, when beeing in contact with the skin.
Executive summary:

The corresponding amine to ZDMC is DMA, and both substances are able to challenge an allergic dermatitis.

Thesis: allergenic compounds with a dimethylamino substituent, such as TMTD, TMTM, ZDMC and DMA should not be compounded in rubber gloves worn in direct contact with the skin.

In earlier investigations DMA and ZDMC were already identified as agents which cross-react with TMTD.

Additionally, in the thesis is reported, that causative are the agents DTCs but later the patients react to thiurams (non-causative and cross-reactive DTC).

So hypothesis: DTCs such as ZDMC, ZDEC, ZDBC and ZEPC and amines such as DMA, DEA and PIP, should be paid great attention to as noteworthy causative candidates in cases of allergic contact dermatitis from rubber gloves. Thiurams are then usefull to detect sensitization to DTCs and /or amines.