PMID- 10617213
OWN - NLM
STAT- MEDLINE
DCOM- 20000330
LR  - 20190721
IS  - 0105-1873 (Print)
IS  - 0105-1873 (Linking)
VI  - 41
IP  - 6
DP  - 1999 Dec
TI  - Influence of application vehicle on skin sensitization to 
      methylchloroisothiazolinone/methylisothiazolinone: an analysis using the local 
      lymph node assay.
PG  - 325-9
AB  - The murine local lymph node assay (LLNA) is a method for the identification of 
      skin sensitizing chemicals in which activity is measured as a function of 
      proliferative responses induced in draining lymph nodes following topical 
      exposure of mice to the test material. More recently, the LLNA has also been used 
      for the determination of relative skin sensitizing potency based upon the 
      mathematical derivation of an EC3 value, this being the estimated concentration 
      of test chemical necessary to provoke a 3-fold increase in lymph-node 
      cell-proliferative activity compared with concurrent vehicle-treated controls. 
      Here we describe the use of the LLNA to determine the influence of vehicle on the 
      skin-sensitizing potency of methylchloroisothiazolinone/methylisothiazolinone 
      (MCI/MI), the active ingredient of preservatives such as Kathon CG. To this end, 
      LLNA responses to MCI/ MI were measured using the vehicles 4:1 acetone:olive oil 
      (AOO), methyl ethyl ketone, dimethylsulfoxide, dimethylformamide, propylene 
      glycol (PG) and acetone. It was found that the vehicle in which MCI/MI was 
      applied had a substantial impact on activity, with derived EC3 values varying 
      from 0.0049% with AOO to 0.048% with PG. With the other vehicles, EC3 values 
      ranged from 0.0068 to 0.0076%. The skin sensitizing potency of MCI/MI as judged 
      from LLNA responses is consistent with what is known of the requirements for 
      sensitization in humans. It is proposed that the LLNA not only provides a method 
      for determination of relative skin sensitizing potency, but is also appropriate 
      for assessing the influence of vehicle matrix on sensitizing activity.
FAU - Warbrick, E V
AU  - Warbrick EV
AD  - AstraZeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
FAU - Dearman, R J
AU  - Dearman RJ
FAU - Basketter, D A
AU  - Basketter DA
FAU - Kimber, I
AU  - Kimber I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Contact Dermatitis
JT  - Contact dermatitis
JID - 7604950
RN  - 0 (Allergens)
RN  - 0 (Pharmaceutical Vehicles)
RN  - 0 (Thiazoles)
SB  - IM
MH  - Allergens/*adverse effects
MH  - Animals
MH  - Dermatitis, Allergic Contact/*etiology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Lymph Nodes/pathology
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Patch Tests
MH  - Pharmaceutical Vehicles/*adverse effects
MH  - Thiazoles/*adverse effects
EDAT- 2000/01/05 09:00
MHDA- 2000/04/01 09:00
CRDT- 2000/01/05 09:00
PHST- 2000/01/05 09:00 [pubmed]
PHST- 2000/04/01 09:00 [medline]
PHST- 2000/01/05 09:00 [entrez]
AID - 10.1111/j.1600-0536.1999.tb06181.x [doi]
PST - ppublish
SO  - Contact Dermatitis. 1999 Dec;41(6):325-9. doi: 
      10.1111/j.1600-0536.1999.tb06181.x.