Francesca Caloni

Animal poisoning in Europe. Part 2: Companion animals

This is the second in a series of three review articles on animal poisoning in Europe and focuses on cases in pet animals and horses in five European countries (Belgium, France, Greece, Italy and Spain) reported over the last decade. In the participating countries, dogs were the most commonly poisoned species, particularly younger animals. The majority of cases in companion animals resulted from exposure to insecticides, although rodenticides (especially anticoagulants and strychnine) posed a significant risk. In all five countries, horses and cats appeared to be more susceptible to plant toxins. Intoxications with herbicides, metals, household products and drugs for veterinary and human use were reported sporadically. The review demonstrates the importance of increased awareness so as to minimise poisoning episodes and emphasises the need to establish a European system for the recording of poisoning data.

Animal poisoning in Europe. Part 3: Wildlife

This review article is the third in a series on animal poisoning in Europe and represents a collation of published and non-published wildlife poisoning data from Belgium, France, Greece, Italy and Spain over the last 10 years. Birds, particularly waterfowl and raptors, were more commonly reported as victims of poisoning than wild mammals. In addition to specific but important toxicological disasters, deliberate primary or secondary poisonings are of concern to all countries. Metals (particularly lead arising from sporting/hunting activities) and pesticides (mainly anticholinesterases and anticoagulants) are frequent causes of poisoning, and often have fatal consequences. A more unified and consistent approach throughout European countries to improve the reporting and the analytical confirmation of wildlife poisoning would help to reduce the number of cases of malicious or negligent animal poisoning.

Animal poisoning in Europe. Part 1: Farm livestock and poultry.

The lack of a reference Veterinary Poison Control Centre for the European Union (EU) means that clinicians find it difficult to obtain information on poisoning episodes. This three-part review collates published and unpublished data obtained from Belgium, France, Greece, Italy and Spain over the last decade in order to provide a broader toxicoepidemiological perspective. The first article critically evaluates the national situation in the five European countries and concludes that information for livestock and poultry is limited and fragmentary compared to other animal groups. The analysis has revealed that clinical cases of poisoning are only occasionally studied in depth and that cattle are the species most frequently reported. Several plants and mycotoxins, a few pesticides and metals, together with contaminants of industrial origin, such as dioxins, are responsible for most of the recorded cases.

Caco-2/tc7 cell line characterization for intestinal absorption : how reliable is this in vitro model for the prediction of the oral dose fraction absorbed in human?

Caco-2 cell line is one of the most used in vitro model to study intestinal absorption of compounds at screening level. Several clones have been isolated from Caco-2 cell line and characterized for their activities. Among them, TC7 clone was isolated from a late passage of the parental Caco-2 line and has shown to consist of a more homogeneous population with respect to the most representative functions of the small intestinal enterocytes, with more developed intercellular junctions. On the basis of these characteristics, it was selected within the framework of the EU A-Cute-Tox project to check its suitability to predict intestinal transport. In the present study, drugs, synthetic or natural chemicals have been characterized for their absorption profile in TC7 cells cultivated on semi-permeable filters for 21 days. The absorption experiments have been performed with the highest nontoxic concentration as determined in a preliminary set of cytotoxicity tests. The apparent permeability coefficient (P(app)) has been extrapolated by calculating the passage of the test compound from the donor to the receiver compartment as a time function. The samples have been collected at different time intervals and the concentration of the test compounds analyzed by analytical methods (HPLC, GC, GC/MS). The P(app) obtained with the TC7 clone are comparable to those obtained with the parental cell line. However, some drawbacks related to the experimental system have been highlighted (i.e. low mass balance, adsorption to the plastics), on the basis of which some compounds were excluded from the analysis. In order to check the predictability of the model, a regression analysis has been performed by plotting P(app) values vs. the fraction absorbed in humans (FA, expressed as % of the administered dose). Additional elaborations have highlighted that the specific absorption pathway (passive, active and carrier-mediated) and other factors (i.e. efflux proteins and/or metabolic activity) can strongly affect the robustness of the prediction model. On the basis of the obtained results, TC7 clone has shown to be a model for passive diffusion as reliable as the parental cell line. However, we have remarked the non-suitability of the TC7 cells to predict intestinal absorption: (i) for highly lipophilic compounds; (ii) for poorly absorbed compounds; or (iii) when transporter-mediated routes and/or first pass metabolism are involved. The preliminary study of those factors likely influencing compound biokinetics, as well as the characterization of the cellular model with respect to metabolic and transporter competence, would help in the interpretation of data.

Dioxin and PCB contamination of fish and shellfish: Assessment of human exposure. Review of the international situation

Abbreviations: ADI, acceptable daily intake; LOAEL, least observable adverse effect level; NOAEL, no observable adverse effect level; PCB, polychlorinated biphenyl; PCDD/F, polychlorinated dibenzodioxins and dibenzofurans; SCF, Scientific Committee on Food; TCDD, tetrachlorodibenzodioxin; TDI, tolerable daily intake; TEF, toxic equivalency factor; TEQ, toxic equivalent of 2,3,7,8-TCDD; TWI, tolerable weekly intake

Effects of a trichothecene, T-2 toxin, on proliferation and steroid production by porcine granulosa cells

Fusarium mycotoxins, such as trichothecenes and zearalenone, are produced by molds and contaminate a large variety of grains and feedstuffs worldwide. Mycotoxins of Fusarium fungi include the trichothecenes, deoxynivalenol and T-2 toxin (T2), and zearalenone, and have been implicated in poor reproductive performance in pigs. However, direct ovarian effects of T2 toxin have not been reported. Therefore, porcine granulosa cells (GC) from small follicles (1-5mm) were cultured for 2 days in 5% fetal bovine serum and 5% porcine serum-containing medium followed by 2 days in serum-free medium containing various doses of FSH, insulin-like growth factor-I and T2 (at various doses/combinations) to evaluate the influence of T2 on steroid production and cell proliferation. T2 at 1, 3, 30 and 300 ng/mL completely inhibited FSH plus IGF-I-induced estradiol production, whereas 0.3 ng/mL of T2 inhibited estradiol production by 40%. Progesterone production was less sensitive to the inhibitory effects of T2 with 0.3 ng/mL having no effect and 1 ng/mL inhibiting progesterone production by only 30%. At 30 and 300 ng/mL, T2 completely inhibited FSH plus IGF-I-induced progesterone production. The impact of T2 on the dose-response to IGF-I (0, 3, 10 and 30 ng/mL) was also evaluated; T2 blunted the stimulatory effect of 3-30 ng/mL of IGF-I on steroid production and cell proliferation. Serum-induced granulosa cell proliferation was decreased (P<0.05) by 40% after 1 day and by 56% after 2 days of T2 treatment. The present studies indicate for the first time that T2 may be able to alter in growth of the granulosa layer within ovarian follicles in addition to their effect on steroidogenesis. In conclusion, T2 has potent direct dose-dependent effects on granulosa cell proliferation and steroidogenesis. These direct ovarian effects could be one mechanism whereby contaminating Fusarium mycotoxins in feedstuffs could impact reproductive performance in swine.

Effects of fusariotoxins in the equine species.

Fumonisins, trichothecenes and zearalenone are the most commonly occurring Fusarium mycotoxins in cereal grains and animal feed. In this review, the toxicity of these mycotoxins in horses is considered with particular reference to recent data on specific and proposed syndromes. Compared to other animal species, very little information is available on the adverse effects of fusariotoxins in horses. Fumonisin B(1) (FB(1)) is the causative agent of leukoencephalomalacia, which is typified by depression, aimless circling, head pressing, paresis, ataxia, blindness and death. FB(1) has also been shown to cause liver damage and cardiovascular dysfunction. Exposure to deoxynivalenol in conjunction with other fusariotoxins seems to be associated with reduction of feed intake and decrease in bodyweight, whilst the T-2 Fusarium mycotoxin may typically induce oral lesions and zearalenone has been implicated in reproductive disorders. Many questions remain on the synergic effects of fusariotoxins and on a possible relationship between mycotoxins and equine colic.

Toxicological effects of aflatoxins in horses

Aflatoxins are a group of mycotoxins principally produced by Aspergillus flavus and A. parasiticus, which are both natural contaminants of food and feedstuff. Aflatoxin B(1) is the most prevalent member of this group that is normally detected and is the most powerful hepatocarcinogen known. Few naturally occurring episodes of aflatoxicosis in horses have been reported in the literature. Indeed, the published information about aflatoxin exposure, metabolism and the effects on horses is limited and controversial, possibly indicating a lack of awareness rather than the rarity of the occurrence. The target organ in horses, as in other animal species, is the liver and horses suffering from aflatoxicosis show signs of inappetence, depression, fever, tremor, ataxia and cough. Necropsy findings include a yellow-brown liver with centrilobular necrosis, icterus, haemorrhage, tracheal exudates and brown urine. A possible link between aflatoxin exposure and chronic obstructive pulmonary disease has been hypothesised.

Effects of fumonisin B1 alone and combined with deoxynivalenol or zearalenone on porcine granulosa cell proliferation and steroid production.

Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in corn in combination with deoxynivalenol (DON) and zearalenone. The aim of this study was to determine if FB1, alone and combined with DON or α-zearalenol (ZEA), zearalenone major active metabolite, can affect granulosa cell proliferation, steroid production, and gene expression in swine. Porcine granulosa cells were cultured for 2 days in serum-containing medium followed by 1 or 2 days in serum-free medium with or without added treatments. Fumonisin B1 had inhibitory effects on granulosa cell proliferation. Deoxynivalenol strongly inhibited cell growth, and no significant difference was detected in combination with FB1. α-Zearalenol showed a stimulatory effect on granulosa cell numbers even in combination with FB1. Regarding steroid production, FB1 increased progesterone production, and FB1 had no effect on estradiol production. Deoxynivalenol strongly inhibited progesterone and estradiol production, and FB1 had no significant effect on this response. α-Zearalenol increased progesterone production, and its combination with FB1 produced additive effects. α-Zearalenol had no effect on estradiol production, whereas it decreased estradiol production when co-treated with FB1. Fumonisin B1 was found to decrease CYP11A1 messenger RNA abundance, and the stimulatory effect of FB1 on progesterone production was found to be not dependent on 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity suggesting that FB1 increases progesterone production through a different mechanism. The results show that these Fusarium mycotoxins can influence porcine granulosa cell proliferation and steroid production, thereby demonstrating their potential reproductive effects on swine.

Epidemiology of intoxication of domestic animals by plants in Europe

This review focuses on some of the most important poisonous plants in Europe and provides an overview of the poisoning episodes that have occurred in European countries. Poisoning of livestock and companion animals by plants is a relatively common occurrence. In Europe livestock and horses are commonly poisoned by Datura stramonium (Jimson weed), Senecio spp. (ragworts and groundsels), Quercus spp. (oak), Taxus baccata (European yew), Nerium oleander (oleander), Pteridium aquilinum (bracken fern), Robinia pseudoacacia (black locust) and Rhododendron spp. (rhododendrons and azaleas). Poisoning may occur when the fresh plant is ingested in pasture or when it contaminates hay or silage. In pets, the greatest majority of plant poisonings are the result of ingestion of house or garden plants, such as Cycas revoluta (Sago palm), Ricinus communis (castor bean), Allium spp., Euphorbia pulcherrima (poinsettia), Lilium spp., Convallaria majalis (Lily of the valley), Pyracantha spp. (firethorn), Rhododendron spp. (rhododendrons and azaleas), Melia azedarach (Chinaberry tree), Taxus baccata (European yew) and Nerium oleander (oleander).