PMID- 18958734
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20091216
LR  - 20081029
IS  - 1547-6901 (Electronic)
IS  - 1547-691X (Linking)
VI  - 4
IP  - 3
DP  - 2007 Jul
TI  - Effect of Prolonged Repeated Exposure to Formaldehyde Donors with Doses Below the 
      EC3 Value on Draining Lymph Node Responses.
PG  - 239-46
LID - 10.1080/15476910701507967 [doi]
AB  - In the Local Lymph Node Assay (LLNA), a stimulation index of 3 (SI = 3) is 
      established as a threshold value for hazard identification of sensitization. The 
      corresponding EC3 value, the effective concentration inducing a threefold 
      increase compared to controls, can possibly predict threshold levels for 
      sensitization in humans. Exposure to a dose below the threshold dose would not 
      result in an induction of an immune response. Each repeated contact would be 
      considered and viewed as a new contact and as long as the dose is below the 
      threshold there will be no response, even after repeated exposures. However, 
      repeated exposure may result in local accumulation eventually resulting in a dose 
      that induces a response above the threshold for immunization. We investigated 
      lymph node responses after short and prolonged exposure to formaldehyde donors, 
      chemicals that are highly reactive with proteins and may thus persist in the 
      skin. The studies were performed with formaldehyde and formaldehyde releasers 
      (formaldehyde, paraformaldehyde, Quaternium-15, 
      2-Chloro-N-(hydroxymethyl)acetamide, and hexamethylenetetramine), at 
      concentrations that induce a SI = 2, i.e., below the threshold for hazard 
      identification. For all test chemicals investigated enhanced lymph node responses 
      were obtained when comparing long-term prolonged exposure to short-term exposure, 
      while three of five chemicals induced responses above SI = 3. Our results show 
      that repeated and prolonged exposure to doses below the EC3 value can induce 
      reactions above the SI = 3, the hazard identification threshold for sensitization 
      in mice. So, when discussing the possible use of the EC3 as benchmark for risk 
      assessment, one should consider duration of exposure and the possibility of local 
      accumulation of the chemical under investigation.
FAU - De Jong, Wim H
AU  - De Jong WH
AD  - Laboratory for Toxicology, Pathology and Genetics, National Institute for Public 
      Health and the Environment, Bilthoven, The Netherlands. w.de.jong@rivm.nl
FAU - De Klerk, Arja
AU  - De Klerk A
FAU - Beek, Marloes Ter
AU  - Beek MT
FAU - Veenman, Christiaan
AU  - Veenman C
FAU - Van Loveren, Henk
AU  - Van Loveren H
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Immunotoxicol
JT  - Journal of immunotoxicology
JID - 101201960
EDAT- 2008/10/30 09:00
MHDA- 2008/10/30 09:01
CRDT- 2008/10/30 09:00
PHST- 2008/10/30 09:00 [pubmed]
PHST- 2008/10/30 09:01 [medline]
PHST- 2008/10/30 09:00 [entrez]
AID - 781831069 [pii]
AID - 10.1080/15476910701507967 [doi]
PST - ppublish
SO  - J Immunotoxicol. 2007 Jul;4(3):239-46. doi: 10.1080/15476910701507967.