PMID- 26048650
OWN - NLM
STAT- MEDLINE
DCOM- 20160523
LR  - 20210702
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 147
IP  - 1
DP  - 2015 Sep
TI  - A Dose-Response Modeling Approach Shows That Effects From Mixture Exposure to the 
      Skin Sensitizers Isoeugenol and Cinnamal Are in Line With Dose Addition and Not 
      With Synergism.
PG  - 68-74
LID - 10.1093/toxsci/kfv109 [doi]
AB  - Currently, hazard characterization of skin sensitizers is based on data obtained 
      from studies examining single chemicals. Many consumer products, however, contain 
      mixtures of sensitizers that might interact in such a way that the response 
      induced by a substance is higher than predicted in the hazard assessment. To 
      assess interaction of skin sensitizers in a mixture, a dose-response modeling 
      approach is applied. With this approach, it is possible to assess whether or not 
      responses from mixtures of sensitizers can be predicted from the dose-response 
      information obtained from individual chemicals using dose addition. We selected 
      the skin sensitizers isoeugenol and cinnamal, frequently occurring together in 
      consumer products, to be examined in an adjusted local lymph node assay (LLNA). 
      Cell number and cytokine production (IL-10 and IFN-gamma) of the auricular lymph 
      nodes were measured as hallmarks of the skin sensitization response. We found 
      that dose addition for these 2 skin sensitizers closely predicted the effects 
      from mixtures of both chemicals across the broad dose range tested. Hence, 
      isoeugenol and cinnamal show no synergistic effects in the LLNA. Therefore, 
      hazard assessment and risk assessment of these substances can be performed 
      without taking into account mixture exposure.
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of the Society 
      of Toxicology. All rights reserved. For Permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Kienhuis, Anne S
AU  - Kienhuis AS
AD  - *Centre for Health Protection and.
FAU - Slob, Wout
AU  - Slob W
AD  - Centre for Nutrition, Prevention and Health Services, National Institute for 
      Public Health and the Environment (RIVM), 3721 MA Bilthoven, The Netherlands.
FAU - Gremmer, Eric R
AU  - Gremmer ER
AD  - *Centre for Health Protection and.
FAU - Vermeulen, Jolanda P
AU  - Vermeulen JP
AD  - *Centre for Health Protection and.
FAU - Ezendam, Janine
AU  - Ezendam J
AD  - *Centre for Health Protection and janine.ezendam@rivm.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150604
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Complex Mixtures)
RN  - 0 (Cytokines)
RN  - 3T8H1794QW (Eugenol)
RN  - 5M0MWY797U (isoeugenol)
RN  - 7864XYD3JJ (Acrolein)
RN  - SR60A3XG0F (cinnamaldehyde)
SB  - IM
MH  - Acrolein/*analogs & derivatives/toxicity
MH  - Algorithms
MH  - Animals
MH  - Complex Mixtures/*toxicity
MH  - Cytokines/biosynthesis
MH  - Dermatitis, Allergic Contact/*pathology
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Drug Synergism
MH  - Eugenol/*analogs & derivatives/toxicity
MH  - Female
MH  - Local Lymph Node Assay
MH  - Lymph Nodes/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Models, Biological
MH  - Risk Assessment
OTO - NOTNLM
OT  - LLNA
OT  - dose addition
OT  - dose response
OT  - mixture
OT  - skin sensitization
OT  - synergism
EDAT- 2015/06/07 06:00
MHDA- 2016/05/24 06:00
CRDT- 2015/06/07 06:00
PHST- 2015/06/07 06:00 [entrez]
PHST- 2015/06/07 06:00 [pubmed]
PHST- 2016/05/24 06:00 [medline]
AID - kfv109 [pii]
AID - 10.1093/toxsci/kfv109 [doi]
PST - ppublish
SO  - Toxicol Sci. 2015 Sep;147(1):68-74. doi: 10.1093/toxsci/kfv109. Epub 2015 Jun 4.