PMID- 18759875 OWN - NLM STAT- MEDLINE DCOM- 20081210 LR - 20121115 IS - 1600-0536 (Electronic) IS - 0105-1873 (Linking) VI - 59 IP - 2 DP - 2008 Aug TI - Proliferative responses in the local lymph node assay associated with concomitant exposure to 1,4-phenylenediamine and methyldibromo glutaronitrile: evidence for synergy? PG - 90-5 LID - 10.1111/j.1600-0536.2008.01349.x [doi] AB - 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. METHOD: 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. RESULT: 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. FAU - Jowsey, Ian R AU - Jowsey IR AD - Unilever Safety and Environmental Assurance Centre, Colworth Park, Sharnbrook, Bedfordshire, MK44 1LQ, UK. ian.jowsey@smith-nephew.com FAU - Basketter, David A AU - Basketter DA FAU - Irwin, Anita AU - Irwin A LA - eng PT - Journal Article PL - England TA - Contact Dermatitis JT - Contact dermatitis JID - 7604950 RN - 0 (Allergens) RN - 0 (Nitriles) RN - 0 (Phenylenediamines) RN - 0 (Preservatives, Pharmaceutical) RN - U770QIT64J (4-phenylenediamine) RN - YX089CPS05 (1,2-dibromo-2,4-dicyanobutane) SB - IM MH - Allergens/*administration & dosage MH - Animals MH - Cell Proliferation/drug effects MH - Dermatitis, Allergic Contact/*etiology/pathology MH - Drug Interactions MH - Local Lymph Node Assay MH - Lymph Nodes/drug effects/pathology MH - Mice MH - Nitriles/*administration & dosage/toxicity MH - Phenylenediamines/*administration & dosage/toxicity MH - Preservatives, Pharmaceutical/*administration & dosage/toxicity MH - Risk Assessment MH - Skin/*drug effects EDAT- 2008/09/02 09:00 MHDA- 2008/12/17 09:00 CRDT- 2008/09/02 09:00 PHST- 2008/09/02 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/09/02 09:00 [entrez] AID - COD1349 [pii] AID - 10.1111/j.1600-0536.2008.01349.x [doi] PST - ppublish SO - Contact Dermatitis. 2008 Aug;59(2):90-5. doi: 10.1111/j.1600-0536.2008.01349.x.