PMID- 26612505
OWN - NLM
STAT- MEDLINE
DCOM- 20160523
LR  - 20181211
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 339
DP  - 2016 Jan 2
TI  - Reactivity measurement in estimation of benzoquinone and benzoquinone 
      derivatives' allergenicity.
PG  - 34-39
LID - S0300-483X(15)30053-6 [pii]
LID - 10.1016/j.tox.2015.11.002 [doi]
AB  - Benzoquinone (BQ) and benzoquinone derivatives (BQD) are used in the production 
      of dyes and cosmetics. While BQ, an extreme skin sensitizer, is an electrophile 
      known to covalently modify proteins via Michael Addition (MA) reaction whilst 
      halogen substituted BQD undergo nucleophilic vinylic substitution (SNV) mechanism 
      onto amine and thiol moieties on proteins, the allergenic effects of adding 
      substituents on BQ have not been reported. The effects of inserting substituents 
      on the BQ ring has not been studied in animal assays. However, mandated 
      reduction/elimination of animals used in cosmetics testing in Europe has led to 
      an increased need for alternatives for the prediction of skin sensitization 
      potential. Electron withdrawing and electron donating substituents on BQ were 
      assessed for effects on BQ reactivity toward nitrobenzene thiol (NBT). The NBT 
      binding studies demonstrated that addition of EWG to BQ as exemplified by the 
      chlorine substituted BQDs increased reactivity while addition of EDG as in the 
      methyl substituted BQDs reduced reactivity. BQ and BQD skin allerginicity was 
      evaluated in the murine local lymph node assay (LLNA). BQD with electron 
      withdrawing groups had the highest chemical potency followed by unsubstituted BQ 
      and the least potent were the BQD with electron donating groups. The BQD results 
      demonstrate the impact of inductive effects on both BQ reactivity and 
      allergenicity, and suggest the potential utility of chemical reactivity data for 
      electrophilic allergen identification and potency ranking.
CI  - Copyright (c) 2015 Elsevier Ireland Ltd. All rights reserved.
FAU - Mbiya, Wilbes
AU  - Mbiya W
AD  - Department of Chemistry, Portland State University, Portland, OR 97207-0751, 
      United States. Electronic address: wilbesm@gmail.com.
FAU - Chipinda, Itai
AU  - Chipinda I
AD  - Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, 
      National Institute for Occupational Safety and Health, Morgantown, WV 26505-2888, 
      United States.
FAU - Simoyi, Reuben H
AU  - Simoyi RH
AD  - Department of Chemistry, Portland State University, Portland, OR 97207-0751, 
      United States.
FAU - Siegel, Paul D
AU  - Siegel PD
AD  - Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, 
      National Institute for Occupational Safety and Health, Morgantown, WV 26505-2888, 
      United States.
LA  - eng
GR  - CC999999/Intramural CDC HHS/United States
GR  - Y01 ES000001/ES/NIEHS NIH HHS/United States
GR  - IAGY1-ES-0001-12/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20151202
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Allergens)
RN  - 0 (Benzoquinones)
RN  - 0 (Sulfhydryl Compounds)
RN  - 0 (Vinyl Compounds)
RN  - 1849-36-1 (4-nitrothiophenolate)
SB  - IM
MH  - Algorithms
MH  - Allergens/*toxicity
MH  - Animal Testing Alternatives
MH  - Animals
MH  - Benzoquinones/*toxicity
MH  - Dermatitis, Allergic Contact/pathology
MH  - Female
MH  - Local Lymph Node Assay
MH  - Methylation
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Quantitative Structure-Activity Relationship
MH  - Skin/pathology
MH  - Structure-Activity Relationship
MH  - Sulfhydryl Compounds/pharmacology
MH  - Vinyl Compounds/chemistry
PMC - PMC4724239
MID - NIHMS745239
OID - NLM: HHSPA745239 [Available on 01/02/17]
OTO - NOTNLM
OT  - Allergic contact dermatitis
OT  - Benzoquinone
OT  - Local lymph node assay
OT  - Michael addition
OT  - Nucleophilic vinylic substitution
OT  - SNV
OT  - Stimulation index
EDAT- 2015/11/28 06:00
MHDA- 2016/05/24 06:00
PMCR- 2017/01/02
CRDT- 2015/11/28 06:00
PHST- 2015/03/23 00:00 [received]
PHST- 2015/10/27 00:00 [revised]
PHST- 2015/11/11 00:00 [accepted]
PHST- 2015/11/28 06:00 [entrez]
PHST- 2015/11/28 06:00 [pubmed]
PHST- 2016/05/24 06:00 [medline]
PHST- 2017/01/02 00:00 [pmc-release]
AID - S0300-483X(15)30053-6 [pii]
AID - 10.1016/j.tox.2015.11.002 [doi]
PST - ppublish
SO  - Toxicology. 2016 Jan 2;339:34-39. doi: 10.1016/j.tox.2015.11.002. Epub 2015 Dec 
      2.