US EPA

5371262 

Journal Article 

Models for contact sensitization--novel approaches and future developments 

Oliver, GJ; Botham, PA; Kimber, I 

1986 

Yes 

British Journal of Dermatology
ISSN: 0007-0963
EISSN: 1365-2133 

BLACKWELL SCIENCE LTD 

OXFORD 

115 Suppl 31 

31S 

53-62 

English 

3488758 

10.1111/j.1365-2133.1986.tb02110.x 

WOS:A1986F060700012 

The current status of animal tests used for evaluating contact sensitization were reviewed and novel approaches for assessing sensitization potential were discussed. Similarities in current tests include the use of guinea pigs, a protocol with a sensitization phase followed by a challenge phase, the subjective assessment of a skin response, and an evaluation of sensitization potential based on response incidence. Novel approaches discussed concentrate on hapten protein conjugation, T-lymphocyte response following antigen recognition, and antigen presentation. The hapten protein conjugation approach is based on the principle that sensitizing chemicals of low molecular weight appear to require the formation of high molecular weight adducts within the skin before they can be recognized by the immune system. Primary T-lymphocyte responses in the auricular lymph node induced by a variety of nitrobenzene derivatives, including dinitrochlorobenzene (97007) (DNCB), 2,4-dinitrofluorobenzene (70348) (DNFB), 2,4-dinitrothiocyanobenzene (1594565) (DNTB), and 2,4-dichloronitrobenzene (89612) (DCNB) were examined. Their sensitizing capacity in BALB/c-mice was determined after sensitization with the chemical on the flank and subsequent challenge to both ears with reduced concentrations. DNCB, DNFB, and DNTB elicited contact sensitization, while DCNB failed to induce a response. In the antigen presentation approach, the role of both the primary interactive signal (the association between hapten and Langerhans cells) and the secondary amplification signal (epidermal cell thymocyte activating factor) in stimulating a T-cell response in contact sensitivity was researched. Although the way in which topically applied chemicals interact with cells in the skin and the draining lymph nodes is critical in determining whether a T-lymphocyte response occurs, it is not possible to advocate a determinant selection hypothesis for the mechanism of contact sensitivity. The authors conclude that the need for continued improvement in methods for identifying contact sensitizers was displayed.