Exposure to methylmercury due to consumption of fish in the Mediterranean

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Abstracts / Toxicology Letters 164S (2006) S1–S324

Supported by UO1-ES010337 and R37-GM18360 from the National Institutes of Health. doi:10.1016/j.toxlet.2006.06.025 18 Neuromuscular function and acetylcholinesterase activity in OP poisoning Horst Thiermann 1 , Ladislaus Szinicz 1 , Peter Eyer 2 , Thomas Zilker 3 , Franz Worek 1 1 Bundeswehr

Institute of Pharmacology and Toxicology, Munich, Germany; 2 Walther-Straub-Institute of Pharmacology and Toxicology, Munich, Germany; 3 Toxicological Department of 2nd Medical Clinic, Technical University, Munich, Germany The most important toxic mechanism in poisoning by organophosphorus compounds (OP) is inhibition of acetycholinesterase (AChE), leading finally to death due to respiratory arrest. The disturbance of physiological functions at the level of muscarinic receptors may be antagonized competitively by antimuscarinics as atropine. However, at the respiratory muscle, namely the diaphragm, nicotinic transmission dominates, calling for other strategies, e.g. reactivation of inhibited AChE, to cope with paralysis. For this purpose, oximes were introduced in therapy about 50 years ago. Although good effectiveness was demonstrated in vitro and in animal studies, their use in human therapy is a matter of debate until now. Such a dispute calls for unravelling the reasons for this ambiguous judgement. In numerous experimental assays it was shown that several oximes are able to reactivate AChE inhibited by several OPs. However, it has to be taken into account that oxime effectiveness is dependent on the oxime itself, the respective OP and its post-inhibitory reactions (ageing, spontaneous reactivation), as well as on the presence of OP. By using the phrenicus-diaphragm preparation of the mouse, it could be shown that obidoxime was able to reactivate muscle AChE inhibited by paraoxon and to restore muscle force when the poison load was not too high. An increase in muscle AChE-activity was associated with an increase in muscle force and almost complete recovery of neuromuscular transmission at AChE levels higher than 40% of control. To assess whether similar effects can be observed in OP-poisoned patients, valuable information have to be extracted from individual clinical cases. To this end, the clinical course of poisoning as well as effectiveness of antidotal therapy were investigated in patients with need of artificial ventilation being treated with atropine and obidoxime.

The analysis revealed that sufficient reactivation of OPinhibited non-aged AChE was possible, if the poison load was not too high and the effective oxime concentrations were administered early and long enough. When RBC-AChE-activity was higher than some 30%, neuromuscular transmission was undisturbed indicating absence of nicotinic signs and symptoms. Accordingly, oximes at appropriate doses, should be given as early as possible and as long as reactivation may be expected. Furthermore, investigation of neuromuscular transmission during OP-poisoning should be included in clinical routine programmes to monitor the course of OP-poisoning. Finally, it was concluded that low atropine dosing (several milligrams) should be sufficient to cope with muscarinic symptoms during oxime therapy. doi:10.1016/j.toxlet.2006.06.026 W2 Mercury—Exposure and Health Effects 19 Exposure to methylmercury due to consumption of fish in the Mediterranean Milena Horvat, Darija Gibiˇcar Jozef Stefan Institute, Ljubljana, Slovenia Daily intakes and retention of mercury from food is generally difficult to estimate accurately. In most food stuffs Hg concentration is below 20 ng/g. Mercury is known to bioconcentrate in aquatic organisms and it is biomagnified in aquatic food webs. For example, mercury in small fish is normally bellow 100 ␮g/kg, while in sward fish, shark and tuna values frequently exceed 1200 ␮g/kg. For that reason, it is generally assumed that population groups dependent on fish protein intake are exposed to higher Hg intake. There are a number of studies carried out at the national level to estimate daily intakes of toxic substances. In case of mercury the main problem is that these reports provide data on total mercury concentrations and the percentage of Hg as monomethylmercury (MeHg) is not known. In some surveys the percentage of Hg originating from fish is provided and it is assumed that the percentage of Hg as MeHg is from 60% to 90%. Therefore fish and fish products represent the major source of MeHg to general population. However, in Hg contaminated sites other food produced in contaminated soil may also contribute considerably to intake of inorganic Hg and MeHg. The Mediterranean region is well known for the elevated presence of Hg due to natural sources. A number of Hg mines were operational for centuries, fos-

Abstracts / Toxicology Letters 164S (2006) S1–S324

sil fuel exploitation (such as oil and natural gas, where Hg is present as a by-product) is also one of the important reason for mercury emissions into the environment. In such regions co-exposure of inorganic Hg and MeHg may occur. The paper will address the outcomes of studies on mercury in fish carried out in the Mediterranean region and compare them with other oceans of the world. Apart from the literature data, the main source of data presented will obtained through Regional Seas Programme of UNEP and the International Atomic Energy Agency. In particular, the Long-term Programme for Pollution Monitoring and Research in the Mediterranean Sea (MED POL) carried out by the Mediterranean Action Plan (MAP) of UNEP through its various phases since 1975 up to now will be presented. This also includes the data management through UNEP-MAP and various studies carried out by the World Health Organization in the period from 1982 to 1988 as well as recent national studies (2000–2005) carried out in Northern Italy and Greece where mercury intakes and consequently elevated Hg concentrations were reported. doi:10.1016/j.toxlet.2006.06.027 20 Health effects of inorganic mercury Lars Barregard Salgrenska University Hospital and Academy, Gotenberg, Sweden The most common exposure to inorganic Hg is by inhalation of mercury vapour (Hg0 ) in occupational settings or from dental amalgam fillings. Low-level exposure occurs via Hg0 in ambient air, and inorganic Hg in the diet. Exposure to methyl mercury (MeHg) results in some inorganic Hg, since MeHg is demethylated in vivo. Exposure is usually assessed using urinary Hg excretion. Typical mean U–Hg levels in the general population of Europe and the US are 0.5–2 ␮g/g creatinine (␮g/gC). The major target organs for inorganic Hg are the central nervous system (CNS) and the kidneys. In the CNS, high exposure causes unspecific symptom, emotional changes, memory loss, and tremor. After shortterm exposure these effects are generally reversible, but persisting CNS damage may occur after long-term exposure. As for the kidney, immunologically mediated nehpritis is rare. Much more common is the effect on renal tubules with an increase in urinary enzymes or low molecular weight proteins. This early effect is generally reversible and not necessarily adverse.

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Recent advances in knowledge are the reports of the growing impact of gold mining on exposure to Hg0 with adverse health effects at heating of gold–mercury amalgam in South America and Asia. For the general population in Europe and the US, high exposure to Hg0 from dental amalgam has been shown in long-term chewing gum users. In contrast, a large EU-funded project (EMECAP) showed that the contribution of Hg0 from air around chloralkali plants is small. In low-level exposed Norwegian and Swedish chloralkali workers reversible effects on renal tubules were recently found at exposure levels of only 10–15 ␮g/gC. There are also effects on selenium metabolism and on the thyroid (inhibition of Se-containing deiodinase), although probably not adverse. Low Se populations may be more vulnerable regarding renal effects of mercury. Some US studies indicate that dentists with very low U–Hg may suffer subtle CNS effects, but this was not confirmed by others. It has been proposed that certain polymorphisms (e.g. CPOX4 ) could affect the sensitivity of CNS to effects of mercury. Two high-quality epidemiological studies on lowlevel exposure to Hg0 were presented this year. More that 1000 children in the US and Portugal were followed for 5–7 years after placement of amalgam or composites, in controlled randomized clinical trials. No effects of amalgam could be shown on the CNS (neurobehavioral tests) or kidneys (microalbuminuria). doi:10.1016/j.toxlet.2006.06.028 21 Mercury exposure in the Amazon, Brazil: Contributions from health studies Volney de M. Camara 1 , Elizabeth Santos 2 1 Federal

Brazil;

University of Rio de Janeiro,Rio de Janeiro, Chagas Institute, Brazil

2 Evandro

This is presenting some studies developed by UFRJ and IEC. A study on Hg exposure levels in 3020 newborns (NB) and mothers from Itaituba, Par´a showed: mercury mean in mothers’ blood 11.53 ␮g/L and the 16.68 ␮g/L for newborns. The correlation between the Hg concentration in newborn and mothers was strongly positive (r = 0.8019; p = 0.000). A comparative research on indoor mercury exposure (n = 365) pointed 13 individuals presenting mercury urine levels up to 86.0 ␮g/L. A research project for preventing indoor burning of mercury–gold amalgams decreased urinary Hg in residents from 2.90 to 1.49 ␮g/L. Researchers in four riverine communities not impacted by goldmining suggested