title: Proliferative responses in the local lymph node assay associated with concomitant exposure to 1,4-phenylenediamine and methyldibromo glutaronitrile: evidence for synergy?
abstract: BACKGROUND
  A key consideration when undertaking risk assessments should be the potential for synergy between contact allergens. Previously, this concept has only been investigated during elicitation in contact allergic individuals.
  
  
  OBJECTIVE
  To determine whether there exists evidence for synergy between contact allergens during the induction phase of skin sensitization using the mouse local lymph node assay (LLNA) as a model system.
  
  
  METHODS
  Proliferative responses in draining lymph nodes were assessed with increasing concentrations of 1,4-phenylenediamine (PPD), methyldibromo glutaronitrile (MDBGN), and a combination of PPD and MDBGN.
  
  
  RESULTS
  Data from each of two independent experiments show that lymph node cell proliferation associated with combined exposure to PPD and MDBGN was, in general, only modestly increased relative to that predicted from a simple summation of their individual responses.
  
  
  CONCLUSIONS
  Although the increase in response is very modest, it does imply a relationship between this combination of sensitizers that may not be simply additive in terms of their ability to stimulate proliferative responses in draining lymph nodes. The reproducibility of this observation should be confirmed in future studies with additional pairs of contact allergens to ascertain whether or not this represents evidence of synergy.
authors.affiliation: Unilever Safety and Environmental Assurance Centre, Colworth Park, Sharnbrook, Bedfordshire, MK44 1LQ, UK. ian.jowsey@smith-nephew.com
authors.forename: Ian R
authors.initials: IR
authors.lastname: Jowsey
authors.forename: David A
authors.initials: DA
authors.lastname: Basketter
authors.forename: Anita
authors.initials: A
authors.lastname: Irwin