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ToxSci Advance Access originally published online on June 12, 2008
Toxicological Sciences 2008 105(1):79-85; doi:10.1093/toxsci/kfn117
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© The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Interlaboratory Validation of 1% Pluronic L92 Surfactant as a Suitable, Aqueous Vehicle for Testing Pesticide Formulations Using the Murine Local Lymph Node Assay

Darrell R. Boverhof*, Connie M. Wiescinski*, Phil Botham{dagger}, David Lees{ddagger}, Eric Debruyne§, Marina Repetto-Larsay§, Gregory Ladics, Denise Hoban, Armin Gamer||, Marina Remmele||, Weizheng Wang-Fan|||, Ludwig G. Ullmann|||, Jyotigna Mehta||||, Richard Billington|||| and Michael R. Woolhiser*,1

* Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan 48674 {dagger} Syngenta, Jealott's Hill International Research Centre, Bracknell, Berkshire, UK RG42 6EY {ddagger} Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK SK10 4TJ § Bayer CropScience Toxicology Research Centre, Sophia Antipolis, France The DuPont Company, DuPont Haskell Global Centers for Health & Environmental Sciences, Newark, Delaware || Experimental Toxicology and Ecology, BASF SE, 67056 Ludwigshafen, Germany ||| RCC Ltd, CH-4452 Itingen, Switzerland |||| Human Health Assessment, Dow AgroSciences Limited, Abingdon, UK

1 To whom correspondence should be addressed at The Dow Chemical Company, Toxicology and Environmental Research & Consulting, 1803 Building, Midland, MI 48674. Fax: (989) 638-9305. E-mail: MWoolhiser{at}dow.com

Received April 30, 2008; accepted May 30, 2008


  Abstract

The mouse local lymph node assay (LLNA) has become the preferred test for evaluating the dermal sensitization potential of chemicals and requirements are now emerging for its use in the evaluation of their formulated products, especially in the European Union. However, despite its widespread use and extensive validation, the use of this assay for directly testing mixtures and formulated products has been questioned, which could lead to repeat testing using multiple animal models. As pesticide formulations are typically a specific complex blend of chemicals for use as aqueous-based dilutions, traditional vehicles prescribed for the LLNA may change the properties of these formulations leading to inaccurate test results and hazard identification. The objective of this study was to evaluate the effectiveness of an aqueous solution of Pluronic L92 block copolymer surfactant (L92) as a vehicle in the mouse LLNA across five laboratories. Three chemicals with known sensitization potential and four pesticide formulations for which the sensitization potential in guinea pigs and/or humans had previously been assessed were used. Identical LLNA protocols and test materials were used in the evaluation. Assessment of the positive control chemicals, hexylcinnamaldehyde, formaldehyde, and potassium dichromate revealed positive results when using 1% aqueous L92 as the vehicle. Furthermore, results for these chemicals were reproducible among the five laboratories and demonstrated consistent relative potency determinations. The four pesticide formulations diluted in 1% aqueous L92 also demonstrated reproducible results in the LLNA among the five laboratories. Results for these test materials were also consistent with those generated previously using guinea pigs or from human experience. These data support testing aqueous compatible chemicals or pesticide formulations using the mouse LLNA, and provide additional support for the use of 1% aqueous L92 as a suitable, aqueous-based vehicle.

Key Words: toxicity; acute; LLNA; sensitization.


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