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Abstracts / Toxicology L

n the brain, while other analogues were found in other tissuess well as in feed, stomach content and vomit. Furthermore, theathological examination showed damage in the cerebellum. Com-arative studies of the in vivo tremorgenic effects of penitrem And analogues showed higher potency of penitrem A. Studies usingrain preparations demonstrated region-specific receptor bindingrofiles suggesting allosteric modulation of these receptors in fore-rain and convulsant-like effect in cerebellum. We conclude thatenitrem A is a potent neurotoxin affecting dogs and the toxicechanism may, at least partly, be due to effects on brain receptors.

oi:10.1016/j.toxlet.2012.03.231

06-13xperimental pigweed poisoning in Iranian fat-tailed sheep

halil Badiei, Mehrdad Pourjafar, Saeid Nazifi, Mohsen Ghane,asim Pakniat

School of Vet Med, Shiraz University, Iran

Poisonous plants can cause serious injury to animals, particu-arly if they graze. Purslane (also known as pigweed) is an ediblelant that is cultivated in Fars province (Iran) and may be con-umed by ruminants with a risk of poisoning. As field cases occurccasionally in this region our aim was to induce pigweed poison-ng experimentally to reveal more information on this poisoning inheep.

In this experiment 5 Iranian fat tailed sheep aged 8 to 10 monthsere used. Before the experiment all the animals were kept in stan-ard conditions for 2 weeks and fed hey. After that, for the first 3ays of the experiment, all animals were fed hey and purslane, inqual parts. Between the third to seventy days, the animals wereed only purslane and water ad libitum.

During the experimental period clinical signs in animalsncluded diarrhea, weakness, increased heart and respiratory rates.fter slaughtering the animals, liver and kidney damage and con-estion of lung and brain tissues were detectable. Increased activityf serum AST and GGT enzymes and significant increases in con-entration of serum creatinin, methemoglobin, haptoglobin, serummyloid A were observed at different time intervals. Haematologyevealed leukocytosis, neutrophilia, lymphopenia and significantp < 0.05) decrease of PCV and red blood cell counts. It has beentated that vascular damage by calcium oxalate monohydrate andhe nitrate content of the plant are major causes of these changes.he kidney damage may be related to precipitation of the calciumxalate monohydrate crystals in renal tubules.

oi:10.1016/j.toxlet.2012.03.232

06-14systematic comparison between young and older workers:

andling chemicals exposure

laude Emond

University of Montreal, Canada

Purpose: As a person ages, the body changes, and the efficiencyf functions that ensure homeostasis is reduced. Therefore, it is rea-onable to expect that the impacts on the ability of older workers to

anage stress might be different in comparison to younger work-

rs. The aim of this work was to analyze changes in the physiologicalnd biochemical parameters that may influence the responses

211S (2012) S43–S216 S59

of older workers to chemical exposures regardless of theirages.

Methods: For this project, we conducted a comprehensive lit-erature review, using research tools such as MEDLINE, TOXNET,and other specialized medical books and references. We proposedgrouping workers by stratum to compare different age groups (peo-ple aged between 18 and 70 years). This approach fills the gapsin which the loss of capacity reduces the body’s ability to handlechemical exposures.

Results and conclusion(s): The results suggest that many physio-logical systems change with age. For example, the gastrointestinaltransit decreases with age, thereby increasing the residence timeof drugs and possibly the amount absorbed. A decrease of liver per-fusion with age can increase the half-life of chemical reactivity;however, it does not seem that cytochrome P450 changes with age.A decrease in hepatic drug metabolism observed with age mightbe related to a reduction in organ mass. Using this approach, thelevels of physiological and biochemical parameters are extracted,compiled, and compared. Physicians and toxicologists in occupa-tional health may use the results to identify constraints for agingworkers with a perspective view toward prevention.

doi:10.1016/j.toxlet.2012.03.808

P07: Computational Toxicology

P07-01A novel infrastructure for chemical safety predictions withfocus on human health

Ola Spjuth 1, Egon Willighagen 2, Ulf Hammerling 3, LennartDencker 1, Roland Grafström 2

1 Uppsala University, Sweden, 2 Karolinska Institutet, Sweden,3 National Food Administration, Sweden

A major objective of Computational Toxicology is to provide reli-able and useful estimates in silico of (potentially) harmful actionsof chemicals in humans. Predictive models are commonly based onin vitro and in vivo data, and aims at supporting risk assessmentin various areas, including the environmental protection, food, andpharmaceutical sectors. The field is however hampered by the lackof standards, access to high quality data, validated predictive mod-els, as well as means to connect toxicity data to genomics data.

We present a framework and roadmap for a novel public infras-tructure for predictive computational toxicology and chemicalsafety assessment, consisting of: (1) a repository capable of aggre-gating high quality toxicity data with gene expression data, (2)a repository where scientists can share and download predic-tive models for chemical safety, and (3) a user-friendly platformwhich makes the services and resources accessible for the scien-tific community. Databases under the framework will adhere toopen standards and use standardized open exchange formats inorder to interoperate with emerging international initiatives, suchas the FP7-funded OpenTox and ToxBank projects.

The infrastructure will strengthen and facilitate already ongo-ing activities within in silico toxicology, open up new possibilitiesfor incorporating genomics data in chemicals safety modeling(toxicogenomics), as well as deepen the exploitation of signal trans-duction networks. The initiative will lay the foundation needed to

boost decision support in risk assessment in a wide range of fields,including drug discovery, food safety, as well as agricultural andecological safety assessment.

doi:10.1016/j.toxlet.2012.03.234