PMID- 11158712
OWN - NLM
STAT- MEDLINE
DCOM- 20010412
LR  - 20220311
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 59
IP  - 2
DP  - 2001 Feb
TI  - Skin sensitization testing in potency and risk assessment.
PG  - 198-208
AB  - The purpose of this article is to review, and make recommendations for, the use 
      of relevant skin sensitization test methods, for the purposes of determination of 
      relative potency and the threshold dose necessary for the induction of skin 
      sensitization, and for risk assessment. In addressing the first area, the utility 
      of three guinea pig tests (the guinea pig maximization test, the occluded patch 
      test, and the open epicutaneous test) of the local lymph node assay (LLNA) and of 
      human volunteer testing for the assessment of relative potency and identification 
      of thresholds for sensitization were considered. The following conclusions were 
      drawn. (1) Although attempts have been made to modify the guinea pig maximization 
      test for the purposes of deriving dose-response relationships, this method is 
      usually unsuitable for determination of relative sensitizing potency. (2) Guinea 
      pig methods that do not require the use of adjuvant and which employ a relevant 
      route of exposure (the occluded patch test and the open epicutaneous test) are 
      more appropriate for the assessment of relative skin-sensitizing potency. (3) The 
      LLNA is suitable for the determination of relative skin sensitizing potency, and 
      the adaptation of this method for derivation of comparative criteria such as EC3 
      values (the estimated concentration of test chemical required to induce a 
      stimulation index of 3 in the LLNA) provides an effective and quantitative basis 
      for such measurements. (4) For all the methods identified above, potency is 
      assessed relative to other chemical allergens of known skin sensitizing 
      potential. The estimation of likely threshold concentrations is dependent upon 
      the availability of suitable benchmark chemicals of known potency for human 
      sensitization. (5) Human testing (and specifically, the Human Repeat Insult Patch 
      Test) can provide information of value in confirming the absence of skin 
      sensitizing activity of formulations and products under specific conditions of 
      use and exposure. Based on the above, the following recommendations are made. (1) 
      If results are already available from suitable guinea pig tests, then judicious 
      interpretation of the data may provide information of value in assessing relative 
      skin sensitizing potency. This option should be explored before other analyses 
      are conducted. (2) The LLNA is the recommended method for new assessments of 
      relative potency, and/or for the investigation of the influence of vehicle or 
      formulation on skin sensitizing potency. (3) Whenever available, human skin 
      sensitization data should be incorporated into an assessment of relative potency. 
      With respect to risk assessment, the conclusion drawn is that all the available 
      data on skin-sensitizing activity in animals and man should be integrated into 
      the risk-assessment process. Appropriate interpretation of existing data from 
      suitable guinea pig studies can provide valuable information with respect to 
      potency, as the first step in the development of a risk assessment. However, for 
      de novo investigations, the LLNA is the method favored for providing quantitative 
      estimations of skin-sensitizing potency that are best suited to the risk 
      assessment process. Finally, human testing is of value in the risk assessment 
      process, but is performed only for the purposes of confirming product safety.
FAU - Kimber, I
AU  - Kimber I
AD  - Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 
      4TJ, United Kingdom. Ian.Kimber@CTL.zeneca.com
FAU - Basketter, D A
AU  - Basketter DA
FAU - Berthold, K
AU  - Berthold K
FAU - Butler, M
AU  - Butler M
FAU - Garrigue, J L
AU  - Garrigue JL
FAU - Lea, L
AU  - Lea L
FAU - Newsome, C
AU  - Newsome C
FAU - Roggeband, R
AU  - Roggeband R
FAU - Steiling, W
AU  - Steiling W
FAU - Stropp, G
AU  - Stropp G
FAU - Waterman, S
AU  - Waterman S
FAU - Wiemann, C
AU  - Wiemann C
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Allergens)
SB  - IM
MH  - Allergens/*toxicity
MH  - Animals
MH  - Dermatitis, Allergic Contact/*etiology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Guinea Pigs
MH  - Humans
MH  - Local Lymph Node Assay
MH  - Mice
MH  - Risk Assessment
MH  - Skin Tests/*methods/standards
RF  - 76
EDAT- 2001/02/07 11:00
MHDA- 2001/04/17 10:01
CRDT- 2001/02/07 11:00
PHST- 2001/02/07 11:00 [pubmed]
PHST- 2001/04/17 10:01 [medline]
PHST- 2001/02/07 11:00 [entrez]
AID - 10.1093/toxsci/59.2.198 [doi]
PST - ppublish
SO  - Toxicol Sci. 2001 Feb;59(2):198-208. doi: 10.1093/toxsci/59.2.198.