PMID- 18568891
OWN - NLM
STAT- MEDLINE
DCOM- 20080924
LR  - 20101118
IS  - 1556-9535 (Electronic)
IS  - 1556-9527 (Linking)
VI  - 27
IP  - 2
DP  - 2008
TI  - The impact of vehicle on the relative potency of skin-sensitizing chemicals in 
      the local lymph node assay.
PG  - 67-75
LID - 10.1080/15569520801904655 [doi]
AB  - The identification and characterization of chemicals that possess 
      skin-sensitizing potential are typically performed using predictive tests. 
      However, human exposure to skin-sensitizing chemicals often occurs via a matrix 
      (vehicle) that differs from that used in these tests. It is thus important to 
      account for the potential impact of vehicle differences when undertaking 
      quantitative risk assessment for skin sensitization. This is achieved through the 
      application of a specific sensitization assessment factor (SAF), scaled between 1 
      and 10, when identifying an acceptable exposure level. The objective of the 
      analysis described herein is to determine the impact of vehicle differences on 
      local lymph node assay (LLNA) EC3 values (concentrations of test chemical 
      required to provoke a 3-fold increase in lymph node cell proliferation). 
      Initially, the inherent variability of the LLNA was investigated by examining the 
      reproducibility of EC3 values for 14 chemicals that have been tested more than 
      once in the same vehicle (4:1 acetone:olive oil, AOO). This analysis reveals that 
      the variability in EC3 value for these chemicals following multiple assessments 
      is <5-fold. Next, data from the literature and previously unpublished studies 
      were compiled for 18 chemicals that had been assessed in the LLNA using at least 
      2 of 15 different vehicles. These data demonstrate that often the variability in 
      EC3 values observed for a given chemical in different vehicles is no greater than 
      the 5-fold inherent variability observed when assessing a chemical in the same 
      vehicle on multiple occasions. However, there are examples where EC3 values for a 
      chemical differ by a factor of more than 10 between different vehicles. These 
      observations were often associated with an apparent underestimation of potency 
      (higher EC3 values) with predominantly aqueous vehicles or propylene glycol. 
      These data underscore the need to consider vehicle effects in the context of 
      skin-sensitization risk assessments.
FAU - Jowsey, Ian R
AU  - Jowsey IR
AD  - Unilever Safety and Environmental Assurance Centre, Colworth Park, Sharnbrook, 
      Bedfordshire, UK. ian.jowsey@smith-nephew.com
FAU - Clapp, Catherine J
AU  - Clapp CJ
FAU - Safford, Bob
AU  - Safford B
FAU - Gibbons, Ben T
AU  - Gibbons BT
FAU - Basketter, David A
AU  - Basketter DA
LA  - eng
PT  - Journal Article
PL  - England
TA  - Cutan Ocul Toxicol
JT  - Cutaneous and ocular toxicology
JID - 101266892
RN  - 0 (Allergens)
RN  - 0 (Organic Chemicals)
RN  - 0 (Pharmaceutical Vehicles)
RN  - 0 (Solvents)
SB  - IM
MH  - Allergens/*pharmacology
MH  - Animals
MH  - Cell Proliferation/*drug effects
MH  - Dermatitis, Allergic Contact/*etiology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Immunization/*methods
MH  - *Local Lymph Node Assay
MH  - Lymph Nodes/*drug effects
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Organic Chemicals/pharmacology
MH  - Pharmaceutical Vehicles/*pharmacology
MH  - Reproducibility of Results
MH  - Risk Assessment
MH  - Solvents/pharmacology
EDAT- 2008/06/24 09:00
MHDA- 2008/09/25 09:00
CRDT- 2008/06/24 09:00
PHST- 2008/06/24 09:00 [pubmed]
PHST- 2008/09/25 09:00 [medline]
PHST- 2008/06/24 09:00 [entrez]
AID - 793841890 [pii]
AID - 10.1080/15569520801904655 [doi]
PST - ppublish
SO  - Cutan Ocul Toxicol. 2008;27(2):67-75. doi: 10.1080/15569520801904655.