Neurobehavioural effects of pesticides with special focus on organophosphorus compounds: which is the real size of the problem?

The risk of neurobehavioural impairment as a consequence of a prolonged, low dose exposure to neurotoxic pesticides is not clearly demonstrated despite numerous publications addressing the topic. We reviewed the 24 papers published on human neurobehavioural effects of organophosphorus and/or carbamates pesticides up to May 1st 2008. Variables evaluated were compound/s addressed, number of subjects, approach to measure or estimate exposure, characteristics of control groups and presence of confounders, methodological approach, and type of alteration, taking into account cognitive, sensory-motor, psychological, and psychomotor measures. A total of 6 papers considered the whole spectrum of functions, the studies yielding positive or uncertain results were 13 (68%) for cognitive function, 11 (69%) for psychomotor function, 11 (65%) for sensory-motor function, and 11 (65%) for psychological function impairment. In 46% of the positive studies a previous severe acute poisoning was reported. Exposure levels were measured only in 5 studies, and very often there were problems in the selection of controls, and firm conclusions on the risk of neurobehavioural effects cannot be reached yet. The main limits of the available data are: limited number of studies and compounds addressed, significant differences in the approach among studies, poor concordance of the results of different studies, and difficulties in controlling confounding factors. Nevertheless, there are sufficient data to conclude that neurobehavioural impairment might be the consequence of an acute poisoning, and possibly the consequence of relatively high and prolonged exposures.

[The impact of personal protective equipment in reducing risk for operators exposed to pesticides: from theory to practice]. / La stima dell'impatto dei dispositivi di protezione nella riduzione del rischio in ambito di regolamentazione dei prodotti fitosanitari: dalla teoria alla pratica.

In Europe, the use of plant protection products is authorized provided the operator risk assessment carried out does not show exposure levels above the health-based triggers. Two models are currently available (German and UK models) to estimate exposure levels of agricultural operators. They consider, among different variables, the use of Personal Protective Equipment (PPE), based on their capacity to reduce exposure through the application of specific "reduction factors", derived from laboratory or field studies. Such factors, which date back to '90s, could be obsolete, as indicated by recent literature, posing problems on the reliability of current estimates. Therefore, the exposure estimates produced in Europe from 2005 to 2007, for 52 active ingredients in 395 scenarios, have been collected and analysed to check whether the application of recent exposure reduction factors might have an impact on the final outcomes. In some case the exposure levels resulted underestimated, highlighting the problem of operator safety with regard to the use of specific PPE and to an adequate training programme.

[Definition of acceptable operator exposure levels (AOELs) to pesticides]. / La definizione di livelli accettabili di esposizione ad antiparassitari per l'operatore (AOELs).

A guidance document entitled "Recommended method for the establishment of Acceptable Operator Exposure Levels" has been prepared within the EU 5th Framework program. The paper describes the main outcomes of the project and the issues that apply particularly to agricultural workers and bystanders and the difficulties in developing an agreed uniform approach. The scientific basis of the process is discussed, to be used by the European Commission and Member States when making decision about the inclusion of an active substance in Annex 1 of Directive 91/414/EEC.

Neurobehavioral effects of pesticides: state of the art.

The authors have reviewed the literature on neurobehavioral toxicity of pesticides to assess the status of knowledge on this matter. Some data suggest that exposure to DDT and fumigants may be associated with permanent decline in neurobehavioral functioning and increase in psychiatric symptoms, but, due to the limited number of studies available and the scarce knowledge on exposure levels, no firm conclusion can be drawn. Data on subjects acutely poisoned with organophosphorous compounds suggest that an impairment in neurobehavioral performance and, in some cases, emotional status may be observed as a long-term sequela, but the possibility still remains that these effects were only an aspecific expression of damage and not of direct neurotoxicity. Studies carried out on subjects chronically exposed to organophosphates, but never acutely poisoned, do not provide univocal results but the slight changes consistently observed in sheep dippers suggest the need of focusing on activities characterized by relatively higher exposure levels. In general, the main limits of existing knowledge are the variability of the testing methods used, which makes it difficult to compare the results of single studies, and the scarce knowledge on exposure levels. A promising approach may be the conduction of prospective longitudinal or cohort studies, where exposure and dose assessment can be more easily controlled, or the evaluation of cohorts of workers a priori selected for the availability of environmental and biological monitoring data. The follow up of the populations under study may give an answer at the problem of the prognostic significance of the observed changes. Also the protocols used to assess neurobehavioral functioning need to be standardized.

[Occupational exposure to fungicides in floriculture in Ecuador]. / Esposizione professionale a fungicidi in floricoltori dell'Ecuador.

Floriculture represents one of the major sources of income in the Ecuadorian Andean Region that can be carried out either in open fields as in greenhouses by using chemical compounds, growing hormones and xenobiotics. Among pesticides, ethylenbisdithiocarbamate (EBDTCs) fungicides represent the most extensively used. The aim of the study was the assessment of exposure to EBDTCs in Ecuadorian floricultural workers by the determination of the urinary excretion of the main metabolite of these compounds, ethylenethiourea (ETU). For this purpose, thirty-six floriculture workers and 7 unexposed healthy subjects were recruited for the study. Median level of ETU excretion in agricultural workers before the work shift was 3.2 micrograms/g creatinine, ranging from 0.4 to 34.5 micrograms/g creatinine. After pesticide application, urinary ETU increased to 6.2 micrograms/g creatinine (1.5-26.5) microgram/g creatinine. Urinary ETU resulted significantly higher in overall workers, taken as pre- and post-shift samples, when compared to controls (0.7, 0.4-2.1 micrograms/g creatinine, p < 0.01). According to jobs, applicators showed the highest levels of ETU excretion whereas growing, post-harvesting and maintenance workers showed similar levels of exposure. Higher level ETU excretion was observed in greenhouse compared to open field workers.

[Risk profiles in agriculture: activities in the region of Lombardy]. / Profili di rischio in agricoltura: attività in Regione Lombardia.

Agriculture represents a very complex scenario that needs proper tools. To this aim, in the frame of Special Project "La Prevenzione nell'impiego di Antiparassitari in Agricoltura" promoted by the Region of Lombardy, profiles of exposure and/or risk have been identified as valid approach able to define particular conditions of exposure and risk for the operator in particular settings. The evaluation necessarily needs to identify the most important parameters affecting exposure and their extent on magnitude of exposure. Therefore, field studies should be further performed in order to confirm and improve the profile. The identification of profiles of exposure and risk is an activity still in progress that need to be carefully set up and standardised. The team involved in the study identified priorities deserving much attention in Lombardy, and planned a three years programme aimed at define the profile of exposure and risk in viticulture, maize crop, rice growing, nursery gardening, horticulture in greenhouses, maintenance of gardens, and poplar growing.

Ethylenethiourea in urine as an indicator of exposure to mancozeb in vineyard workers.

In the present study, the personal exposure to mancozeb and/or ethilenethiourea (ETU) in 13 Italian vineyard workers and in 13 subjects without occupational exposure to pesticides was investigated. With this aim, the level of ETU in urine and the dermal exposure to mancozeb were determined. Baseline urinary ETU results were lower than the analytical limit of detection for all controls (<0.5 microg/g creatinine) and for ten workers (median <0.5, range <0.5-3.4 microg/g creatinine). In workers, urinary ETU was significantly increased at the end of shift (2.5, <0.5-95.2 microg/g creatinine) compared with baseline levels. End-shift urinary ETU was higher in operators using open tractors (n=7) than in those using closed tractors (n=5) (16.2 vs. 2.4 microg/g creatinine), but the difference was not significant (P=0.073). End-shift urinary ETU was positively correlated with dermal exposure to mancozeb determined both over the clothes and on the skin (Spearman's rho=0.770 and 0.702, P=0.009 and 0.024, respectively). Wine consumption positively influenced the excretion of ETU.