PMID- 12176099
OWN - NLM
STAT- MEDLINE
DCOM- 20021011
LR  - 20190901
IS  - 0278-6915 (Print)
IS  - 0278-6915 (Linking)
VI  - 40
IP  - 11
DP  - 2002 Nov
TI  - Examination of a vehicle for use with water soluble materials in the murine local 
      lymph node assay.
PG  - 1719-25
AB  - The murine local lymph node assay (LLNA) is a validated method for identifying 
      skin sensitization hazard. Vehicle choice can influence the sensitization 
      potential of haptens in both the LLNA and in humans, therefore selection of an 
      appropriate vehicle is important. Suggested vehicles for the LLNA include organic 
      solvents and organic-aqueous mixtures. However, due to its high surface tension 
      and poor wetting qualities, water is not recommended and therefore testing 
      aqueous soluble materials can be problematic. The aims of this investigation were 
      to identify a water-based vehicle that possesses better skin wetting properties 
      than water alone, and to assess its performance relative to other solvents in the 
      LLNA using aqueous soluble haptens. The selected wetting agent was the surfactant 
      Pluronic(R) L92 (L92). Concentrations of L92 of up to 50% did not induce positive 
      responses in the LLNA. 1% aqueous L92 was chosen for further examination. 
      Dose-response analyses were performed with dinitrobenzene sulfonic acid (DNBS) 
      and formaldehyde formulated either in water, 1% L92, dimethyl sulfoxide (DMSO) or 
      dimethyl formamide (DMF). Potassium dichromate (PDC) and nickel sulfate were 
      tested in 1% L92, DMSO or DMF. The highest concentration of potassium dichromate 
      was retested in each vehicle and in water to assess the effect of the wetting 
      agent. Estimates of the relative sensitizing potency in each vehicle were 
      determined by calculation of EC3 values (the estimated concentration required to 
      induce a threshold positive response). While DNBS and formaldehyde produced 
      positive responses in all four vehicles, their relative potency varied among the 
      vehicles. The rank ordering of potencies for both materials was, from highest to 
      lowest, DMF > or = DMSO > 1% L92 > water. Compared with water, use of 1% L92 
      resulted in >2-fold increase in potency for DNBS and >3-fold increase for 
      formaldehyde. PDC was positive in DMF, DMSO and 1% L92. The potency ranking was 
      DMF > or = DMSO > 1% L92. Re-evaluation of 0.5% PDC confirmed that formulations 
      of both DMSO and DMF induced strong proliferative responses, whereas somewhat 
      less proliferation was recorded with the 1% L92 vehicle. PDC in water was without 
      activity. The performance of 1% L92 as a vehicle for nickel sulfate was assessed 
      relative to DMSO and DMF. In DMSO, nickel sulfate produced a stimulation index 
      (SI) >3 at only the highest level. Testing in DMF induced low levels of 
      proliferation, but failed to produce a SI of 3 at any concentration tested. When 
      formulated in 1% L92, nickel sulfate caused a SI of 3 when tested at 2.5%. Based 
      on the results of these experiments, for identification of sensitization hazard 
      of aqueous soluble materials using the LLNA, DMF and DMSO are the preferred 
      vehicles. However, if a test material is not soluble in DMF or DMSO, or if higher 
      test concentrations can be achieved in an aqueous vehicle, then 1% L92 may 
      provide a better alternative to water alone in terms of improved assay 
      performance.
FAU - Ryan, C A
AU  - Ryan CA
AD  - The Procter & Gamble Company, Miami Valley Laboratories, PO Box 538707, 
      Cincinnati, OH 45253-8707, USA. ryan.ca@pg.com
FAU - Cruse, L W
AU  - Cruse LW
FAU - Skinner, R A
AU  - Skinner RA
FAU - Dearman, R J
AU  - Dearman RJ
FAU - Kimber, I
AU  - Kimber I
FAU - Gerberick, G F
AU  - Gerberick GF
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Food Chem Toxicol
JT  - Food and chemical toxicology : an international journal published for the British 
      Industrial Biological Research Association
JID - 8207483
RN  - 0 (Allergens)
RN  - 0 (Bacillus licheniformis 86 surfactant)
RN  - 0 (Haptens)
RN  - 0 (Lipoproteins)
RN  - 0 (Solvents)
RN  - 0 (Wetting Agents)
RN  - 059QF0KO0R (Water)
RN  - 143134-35-4 (2,4-dinitrofluorobenzene sulfonic acid)
RN  - 4FLT4T3WUN (nickel sulfate)
RN  - 7OV03QG267 (Nickel)
RN  - 8696NH0Y2X (Dimethylformamide)
RN  - D241E059U6 (Dinitrofluorobenzene)
RN  - T4423S18FM (Potassium Dichromate)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
SB  - IM
MH  - Allergens/immunology
MH  - Animals
MH  - Dermatitis, Allergic Contact/*immunology
MH  - Dimethyl Sulfoxide/immunology
MH  - Dimethylformamide
MH  - Dinitrofluorobenzene/*analogs & derivatives/immunology
MH  - Female
MH  - Haptens/immunology
MH  - Lipoproteins
MH  - Lymph Nodes/*immunology
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Nickel/immunology
MH  - Potassium Dichromate/immunology
MH  - Solubility
MH  - Solvents
MH  - Water
MH  - Wetting Agents
EDAT- 2002/08/15 10:00
MHDA- 2002/10/12 04:00
CRDT- 2002/08/15 10:00
PHST- 2002/08/15 10:00 [pubmed]
PHST- 2002/10/12 04:00 [medline]
PHST- 2002/08/15 10:00 [entrez]
AID - S0278691502001163 [pii]
AID - 10.1016/s0278-6915(02)00116-3 [doi]
PST - ppublish
SO  - Food Chem Toxicol. 2002 Nov;40(11):1719-25. doi: 10.1016/s0278-6915(02)00116-3.