PMID- 14623479
OWN - NLM
STAT- MEDLINE
DCOM- 20040324
LR  - 20220311
IS  - 0273-2300 (Print)
IS  - 0273-2300 (Linking)
VI  - 38
IP  - 3
DP  - 2003 Dec
TI  - Proposal for a risk assessment methodology for skin sensitization based on 
      sensitization potency data.
PG  - 269-90
AB  - In this paper, we propose a quantitative risk assessment methodology for skin 
      sensitization aiming at the derivation of 'safe' exposure levels for sensitizing 
      chemicals, used e.g., as ingredients in consumer products. Given the limited 
      number of sensitizers tested in human sensitization tests, such as the human 
      repeat-insult patch test (HRIPT) or the human maximization test (HMT), we used 
      EC3 values from the local lymph node assay (LLNA) in mice because they provide 
      the best quantitative measure of the skin sensitizing potency of a chemical. A 
      comparison of LLNA EC3 values with HRIPT and HMT LOEL, and NOEL values was 
      carried out and revealed that the EC3, expressed as area dose, can be used as a 
      surrogate value for the human NOEL in risk assessment. The 
      uncertainty/extrapolation factor approach was used to derive (a) an 'acceptable 
      non-sensitizing area dose' (ANSAD) to protect non-allergic individuals against 
      skin sensitization and (b) an 'acceptable non-eliciting area dose' (ANEAD) to 
      protect allergic individuals against elicitation of allergic contact dermatitis. 
      For ANSAD derivation, interspecies, intraspecies and time extrapolation factors 
      are applied to the LLNA EC3. For ANEAD derivation, additional application of a 
      variable sensitization-elicitation extrapolation factor is proposed. Values for 
      extrapolation factors are derived and discussed, the proposed methodology is 
      applied to the sensitizers methylchloroisothiazolinone/methylisothiazolinone, 
      cinnamic aldehyde and nickel and results are compared to published risk 
      assessments.
FAU - Griem, Peter
AU  - Griem P
AD  - Wella AG, Department of Product Safety-Toxicology, Berliner Allee 65, D-64274, 
      Darmstadt, Germany. Peter.Griem@clariant.com
FAU - Goebel, Carsten
AU  - Goebel C
FAU - Scheffler, Heike
AU  - Scheffler H
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Netherlands
TA  - Regul Toxicol Pharmacol
JT  - Regulatory toxicology and pharmacology : RTP
JID - 8214983
RN  - 0 (Allergens)
SB  - IM
MH  - Allergens/adverse effects
MH  - Animals
MH  - *Data Interpretation, Statistical
MH  - Denmark
MH  - Dermatitis, Allergic Contact/etiology/*physiopathology
MH  - Guidelines as Topic
MH  - Humans
MH  - Hypersensitivity/etiology/*physiopathology
MH  - Local Lymph Node Assay
MH  - Mice
MH  - Patch Tests/methods
MH  - *Research Design
MH  - Risk Assessment/*methods
EDAT- 2003/11/19 05:00
MHDA- 2004/03/25 05:00
CRDT- 2003/11/19 05:00
PHST- 2003/11/19 05:00 [pubmed]
PHST- 2004/03/25 05:00 [medline]
PHST- 2003/11/19 05:00 [entrez]
AID - S0273230003000941 [pii]
AID - 10.1016/j.yrtph.2003.07.001 [doi]
PST - ppublish
SO  - Regul Toxicol Pharmacol. 2003 Dec;38(3):269-90. doi: 10.1016/j.yrtph.2003.07.001.