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1 Respiratory and cardiovascular failure are principle toxic effects of β-blocker overdose. Respiratory arrest is the primary cause of death in β-blocker intoxicated rats. 2 The effect of β-adrenoceptor agonists on respiratory and cardiovascular failure in β-blocker overdose was investigated in a model of acute d,l-propranolol (30 mg kg -1 h-1) intoxication in spontaneously breathing rats. 3 Neither the aselective, hydrophilic β-agonist isoprena line (10, 25, 50 μg kg-1 min-1), nor the β 1-selective, lipophilic β-agonist flerobuterol (1,3,10 μ g kg-1 min-1) and the β2-selective, lipophilic β-agonist clenbuterol (10, 25, 50 μg kg-1 min-1) had any beneficial effect on cardiovascular and respiratory variables or survival time in d,l-propranolol intoxicated spontaneously breathing rats. 4 Isoprenaline (10 μg kg-1 min-1) had no favourable effect on haemodynamic and respiratory variables in artificially ventilated d,l -propranolol intoxicated rats either. 5 Addition of dopamine to isoprenaline resulted in a significant reduction of survival time, primarily caused by a decrease in mean arterial blood pressure, in artificially ventilated d,l-propranolol intoxicated rats. Addition of glucagon to isoprenaline did not affect survival time. 6 Artificial ventilation is the most important supportive measure in d,l-propranolol intoxication in the rat.

1 Respiratory and cardiovascular failure are the princi ple toxic effects of β-blocker overdose. Respiratory arrest is the primary cause of death in β-blocker intoxicated rats. 2 The effect of glucagon, dopamine and the combination of glucagon/dopamine on respiratory and cardiovas cular function and survival time in β-blocker overdose was investigated in a model of acute d, l-propranolol (resp. 30 and 15 mg kg-1 h-1 in rat and rabbit) intoxication in spontaneously breathing rats and artifically ventilated rats and rabbits. 3 Glucagon (initial dose of 100 μg kg-1 (bolus), followed by 1 μg kg -1 min-1), dopamine (25 μg kg-1 min-1 ) or the combination of glucagon/dopamine did not im prove survival time (ST) in d, l-propranolol intoxicated spontaneously breathing rats and artificially venti lated rats and rabbits, although some haemodynamic variables i.e. heart rate (HR), mean arterial blood pressure (MAP), left ventricular pressure (LVPmax) and the differentiated left ventricular pressure (LVdp/ dtmax) temporarily improved. 4 Survival time was considerably reduced in d,l- propranolol intoxicated spontaneously breathing and artifically ventilated rats treated with a combination of glucagon /dopamine, which induced a decrease in PaO2 and pH and an increase in PaCO2 partly due to ventilation/perfusion mismatch. 5 The combination of glucagon/dopamine should be used carefully in the treatment of β-blocker overdose in man.

Plant protection products (PPPs) are pesticides containing at least one active substance that drives specific actions against pests (diseases). PPPs are regulated in the EU and cannot be placed on the market or used without prior authorisation. EFSA assesses the possible risks of the use of active substances to humans and environment. Member States decide whether or not to approve their use at EU level. Furthermore, Member States decide at national level on the authorisation of PPPs containing approved substances. In agriculture, exposure to PPPs and their residues during occupational tasks is estimated prior to product authorisation, using models fed with study‐specific (e.g. absorption, dissipation) and default values. Exposure of workers to pesticide residues reduces with the pesticide's dissipation time during crop‐related tasks. However, the current risk assessment gap is that no methodology is available to calculate the re‐entry interval (REI) for workers, which specifies how long they should wear personal protective clothing during their first entry into pesticide‐sprayed crops. Protective clothing (such as gloves) can reduce pesticide residue exposure to an acceptable level of worker safety. Within the European Food Risk Assessment Fellowship Programme (EU‐FORA) assignment, a methodology was developed to calculate agricultural‐use‐specific and pesticide‐specific REIs for which period workers should wear gloves. This was an assignment of the Dutch Ministry of Social Affairs and Employment. Another important aspect of risk assessment to ensure consumer safety is dietary risk assessment. A critical evaluation of residue studies and metabolism of the pesticide in question in crops results in a residue definition for dietary risk assessment and for enforcement and monitoring to define maximum residue limits allowed legally on or in raw agricultural commodities when applying pesticides according to good agricultural practices. This work was assigned by the Dutch Ministry of Health, Welfare and Sport and contributes to the work of the Joint FAO/WHO Meeting on Pesticide Residues.

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