PMID- 20500014
OWN - NLM
STAT- MEDLINE
DCOM- 20110512
LR  - 20131121
IS  - 1537-6524 (Electronic)
IS  - 1537-6516 (Linking)
VI  - 21
IP  - 2
DP  - 2011 Feb
TI  - Hazard identification of strong dermal sensitizers.
PG  - 86-92
LID - 10.3109/15376516.2010.484622 [doi]
AB  - Dermal reactions are the most frequently reported chemical health-related 
      occupational hazard. Identifying dermal sensitizers is important for improving 
      workplace safety. This paper takes a close look at the physico-chemical 
      properties and results from the Local Lymph Node Assay (LLNA) to better 
      understand and predict potent dermal sensitizers. The LLNA was used to identify 
      28 pharmaceutical agents or chemical intermediates as potent dermal sensitizers, 
      EC3 < 1%. Certain parameters were examined to determine if there was any 
      predictability to identify potent dermal sensitizers. These included a computer 
      structure activity analysis using Derek for Windows, molecular weight (Mw), 
      calculated log P, and the log-linear extrapolation approach for estimating the 
      potency. With Derek for Windows, 13 compounds were identified as negative and 15 
      as positive for structural alerts, the most common being haloalkanes, and 
      hydrazines. Additional mechanisms of reactivity were postulated for the remaining 
      compounds. The examination of the Mw showed that all molecules had Mw < 550 Da. 
      For 21 compounds, the interpolated vs extrapolated methods for determining the 
      EC3 value were compared. For eight of the 21 compounds, the extrapolated EC3 was 
      in the correct order of magnitude, eight were incorrect (five were too high and 
      three were too low) and five could not be calculated. The use of a tiered 
      approach including examination of the structural and physico-chemical properties 
      and the LLNA to identify potent dermal sensitizers is integral in the selection 
      of effective safe handling guidance to protect from sensitization hazards.
FAU - Gould, Janet C
AU  - Gould JC
AD  - Pharmaceutical Development, Bristol-Myers Squibb Co., New Brunswick, NJ 08903, 
      USA. janet.gould@bms.com
FAU - Taylor, Stephan
AU  - Taylor S
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20100525
PL  - England
TA  - Toxicol Mech Methods
JT  - Toxicology mechanisms and methods
JID - 101134521
RN  - 0 (Irritants)
RN  - 0 (Pharmaceutical Preparations)
SB  - IM
MH  - Animals
MH  - Dermatitis, Allergic Contact/*etiology/immunology/pathology
MH  - Dose-Response Relationship, Drug
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - Humans
MH  - Irritants/*adverse effects/chemistry/immunology
MH  - Local Lymph Node Assay
MH  - Lymph Nodes/drug effects/immunology/pathology
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Pharmaceutical Preparations/chemistry/classification
MH  - Reproducibility of Results
MH  - Risk Assessment
MH  - Skin/*drug effects
MH  - Structure-Activity Relationship
MH  - Toxicity Tests
EDAT- 2010/05/27 06:00
MHDA- 2011/05/13 06:00
CRDT- 2010/05/27 06:00
PHST- 2010/05/27 06:00 [entrez]
PHST- 2010/05/27 06:00 [pubmed]
PHST- 2011/05/13 06:00 [medline]
AID - 10.3109/15376516.2010.484622 [doi]
PST - ppublish
SO  - Toxicol Mech Methods. 2011 Feb;21(2):86-92. doi: 10.3109/15376516.2010.484622. 
      Epub 2010 May 25.