PMID- 8655100
OWN - NLM
STAT- MEDLINE
DCOM- 19960730
LR  - 20190830
IS  - 0278-6915 (Print)
IS  - 0278-6915 (Linking)
VI  - 34
IP  - 5
DP  - 1996 May
TI  - Preclinical skin sensitization testing of antihistamines: guinea pig and local 
      lymph node assay responses.
PG  - 495-506
AB  - Preclinical test methods for allergic contact sensitivity have been widely used 
      for sensitization hazard identification and, with consideration of human exposure 
      conditions, have also been valuable tools for sensitization risk assessment. For 
      many years, the guinea pig has been the test species of choice with a variety of 
      test methods developed to assess the sensitization response. More recently the 
      local lymph node assay (LLNA) in mice has been developed to provide a more 
      objective index of sensitization potential. The standardized methods have proven 
      to be very well suited to most situations in which potential skin sensitization 
      of a chemical needs to be assessed before human exposure. A potential difficulty 
      with all these relatively limited exposure preclinical test methods, however, is 
      in the ability to detect weak contact allergens that prove to be significant 
      clinical allergens due to chronic topical exposure, exposure to compromised skin, 
      and/or highly exaggerated exposure through transdermal delivery. This has been 
      shown with the transdermal drug clonidine and might also be the case for topical 
      antihistamines. The latter are considered significant clinical contact allergens, 
      although predictive preclinical test data are minimal or lacking. A series of 
      guinea pig (modified Buehler) tests with two common antihistamine compounds 
      (triprolidine and diphenhydramine) and LLNA on these and two other compounds 
      (chlorpheniramine and promethazine) was conducted. Positive Buehler test results 
      required use of penetrating vehicle systems and a modified nine-induction patch 
      regimen. Positive LLNA responses were obtained with all four materials (to 
      varying degrees) only if the application site was pre-abraded or a penetrating 
      vehicle (dimethylformamide) was used. These data support the notion that 
      preclinical sensitization test methods can be modified to increase sensitivity. 
      This may be critical for preclinical assessment of topical/transdermal drugs or 
      other materials with chronic or high-concentration exposures in man.
FAU - Robinson, M K
AU  - Robinson MK
AD  - Human Safety Department, Procter & Gamble Company and Procter & Gamble 
      Pharmaceuticals, Miami Valley Laboratories, Cincinnati, OH 45253, USA.
FAU - Cruze, C A
AU  - Cruze CA
LA  - eng
PT  - Journal Article
PL  - England
TA  - Food Chem Toxicol
JT  - Food and chemical toxicology : an international journal published for the British 
      Industrial Biological Research Association
JID - 8207483
RN  - 0 (Histamine H1 Antagonists)
RN  - 2L8T9S52QM (Triprolidine)
RN  - 3U6IO1965U (Chlorpheniramine)
RN  - 8GTS82S83M (Diphenhydramine)
RN  - FF28EJQ494 (Promethazine)
SB  - IM
MH  - Animals
MH  - Chlorpheniramine/toxicity
MH  - Dermatitis, Allergic Contact/etiology/immunology
MH  - Diphenhydramine/toxicity
MH  - Evaluation Studies as Topic
MH  - Guinea Pigs
MH  - Histamine H1 Antagonists/*toxicity
MH  - Immunologic Tests/*methods
MH  - Lymph Nodes/*drug effects/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred ICR
MH  - Promethazine/toxicity
MH  - Sensitivity and Specificity
MH  - Skin/*drug effects/immunology
MH  - Toxicity Tests
MH  - Triprolidine/toxicity
EDAT- 1996/05/01 00:00
MHDA- 1996/05/01 00:01
CRDT- 1996/05/01 00:00
PHST- 1996/05/01 00:00 [pubmed]
PHST- 1996/05/01 00:01 [medline]
PHST- 1996/05/01 00:00 [entrez]
AID - 0278691596873613 [pii]
AID - 10.1016/0278-6915(96)87361-3 [doi]
PST - ppublish
SO  - Food Chem Toxicol. 1996 May;34(5):495-506. doi: 10.1016/0278-6915(96)87361-3.