Four posters describe studies performed at CXR to investigate the mode of action (MOA) and human relevance of rodent toxicities observed with a number of agrochemicals.  A further poster describes the first in vivo studies to show the utility of double nuclear receptor knockout rats in determining MOA.  The final poster describes a mechanistic approach to characterise absorption of structurally related chemicals to support REACH submissions.

The research presented includes:

• A poster authored with BASF, describing in vitro studies with hepatocytes isolated from constitutive androstane receptor (CAR) knockout rats, and their utility in determining MOA
• A poster authored with BASF  describing in vitro studies to determine the human relevance of CAR-mediated rat hepatocellular tumors
• Two posters reporting in vitro studies performed at CXR to determine the MOA and human relevance of rodent liver tumours.  The first of these is authored with Adama and BASF, the second with Monsanto
• A poster demonstrating the first characterisation of the hepatic effects of Phenobarbital and Pregnenolone 16α-Carbonitrile in CAR and pregnane X receptor (PXR) double knockout rats.
• A poster authored with the H4R REACH Consortium describing the use of everted intestinal sacs to estimate relative absorption of a structurally-related family of chemicals

For further details, please contact johnmcmanus@cxrbiosciences.com , or come see us at stand 520 at SOT.

A full list of posters follows:

Monday Afternoon, March 14, 1:15 PM to 4:30 PM

CC Exhibit Hall

Poster Session: Mixtures, Health and Environmental Impacts of Manmade and Naturally Released Toxicants

Author Attended: 3:00 PM–4:30 PM

#1442 (Poster Board Number P171)

An In Vitro Absorption Screen with Rosin/Resins Using Everted Rat Intestinal Sacs. L.Higgins (1), R. Powrie (1), M. Penman (2), S. Green (2), R. Lobbes (2), L. Rodenburg (2), and C. Elcombe (1).

1: CXR Biosciences, Dundee, United Kingdom; and 2: Hydrocarbon Resins & Rosin Resins REACH Consortium (H4R), Brussels, Belgium.

Tuesday Morning, March 15, 9:30 AM to 12:45 PM

CC Exhibit Hall

Poster Session: Carcinogenesis II

Author Attended: 11:15 AM–12:45 PM

#2068 (Poster Board Number P512)

Prochloraz: Further In Vitro Data Comparing Responses in Male Wild-Type Mouse and Human Cultured Hepatocytes Completes the Human Relevance Framework.

C. Strupp (1), S. Melching-Kollmuss (2), L. Chatham (3), D. Lowes (3), I. Fegert (2), and C. Elcombe (3).

1: Adama Europe, Schaffhausen, Switzerland; 2: BASF SE, Ludwigshafen, Germany; and 3: CXR Biosciences Ltd., Dundee, United Kingdom

Tuesday Afternoon, March 15, 1:15 PM to 4:30 PM

CC Exhibit Hall

Poster Session: Receptors

Author Attended: 3:00 PM–4:30 PM

#2433 (Poster Board Number P456)

Use of Two Compounds to Validate Wild-Type (WT) and Constitutive Androstane Receptor (CAR) Knock-Out Rat Hepatocyte Cultures.

A. Vardy (2), B. Elcombe (2), C. Elcombe (2), I. Fegert (1), M. Goettel (1), and N. Honarvar (1).

1: BASF SE, Ludwigshafen, Germany; and 2: CXR Biosciences, Dundee, United Kingdom.

#2436 (Poster Board Number P459)

Characterisation of the Hepatic Effects of Phenobarbital (PB) and Pregnenolone 16Α-Carbonitrile (PCN) in Constitutive Androstane Receptor (CAR, Nr1i3) and Pregnane X Receptor (PXR, Nr1i2) Double Knockout Rats.

L. Chatham, C. Haines, and C. Elcombe. CXR Biosciences, Dundee, United Kingdom.

Wednesday Morning, March 16, 9:30 AM to 12:45 PM

CC Exhibit Hall

Poster Session: Risk Assessment 3

Author Attended: 11:15 AM–12:45 PM

#2706 (Poster Board Number P213)

Human Relevance of Constitutive Androstane Receptor (CAR)-Mediated Rat Hepatocellular Tumors by Fluxapyroxad.

C. Werner (2), M. Goettel (2), N. Honarvar (2), A. Vardy (3), B. Elcombe (3), C. Elcombe (3), A.M. Doi (1), and I. Fegert (2).

1: BASF Corporation, Research Triangle Park, NC; 2: BASF SE, Ludwigshafen, Germany; and 3: CXR Biosciences Ltd, Dundee, United Kingdom.

Thursday Morning, March 17, 9:30 AM to 12:45 PM

Great Hall A

Poster Session: Late-Breaking Poster Session 3

# 3724 (Poster Board number P416)

Further evaluation of the CAR/PXR MOA and Human Relevance of silthiofam-induced rat liver tumours.

Lynsey Chatham (1), J Kronenberg (2), C Elcombe (1).

1: CXR Biosciences Ltd, Dundee, UK. 2: Monsanto Company, St Louis, USA.