Marco Maroni

Biological monitoring of pesticide exposure: a review of analytical methods.

A wide range of studies concerned with analytical methods for biological monitoring of exposure to pesticides is reviewed. All phases of analytical procedures are assessed, including sampling and storage, sample preparation and analysis, and validation of methods. Most of the studies aimed at measuring metabolites or unchanged compounds in urine and/or blood as biological indicators of exposure or dose. Biological indicators of effect, such as cholinesterase, are also evaluated. The principal groups of pesticides are considered: organophosphorus pesticides, carbamate pesticides, organochlorine pesticides, pyrethroid pesticides, herbicides, fungicides and other compounds. Choice of the method for biological monitoring of exposure depends on the study population: a detection limit of 1 microg/l or less is required for the general population; higher values are adequate for occupationally exposed subjects. Interpretation of results is also discussed. Since biological indices of exposure are only available for a few compounds, biological reference values, established for the general population, may be used for comparison with levels of professionally exposed subjects.

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.

The speciation of the chemical forms of arsenic in the biological monitoring of exposure to inorganic arsenic

Total As content may be determined in blood and urine by means of an AAS method that involves reduction of As to its volatile hydride and ashing at 600 degrees C with MgO and Mg (NO3)2. Separation of inorganic As (InAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMAA) by ion-exchange chromatography, followed by direct AAS analysis, allows the determination of each As species in the urine. In a reference population of 148 subjects with only normal environmental exposure to As, total As concentration in the urine averages 17.2 +/- 11.1 micrograms/l. Urinary As consists of 10% each of InAs, MMAA and DMAA, the remaining 70% consisting of other forms of organic As. Blood As concentration averages 5.1 +/- 6.9 micrograms/l and correlates significantly with the urinary concentration of InAs and the sum of its metabolites (InAs + MMAA + DMAA). Inorganic arsenic undergoes methylation in the organism. After ingestion of high quantities of As2O3, the time course of excretion of its metabolites indicates that As methylation occurs by a saturable mechanism. In workers exposed to As2O3, InAs, MMAA and DMAA are the only chemical forms of As excreted in the urine that are relevant to a study of occupational exposure. Blood As concentration is proportional to exposure and correlates only with urinary DMAA excretion; DMAA seems to be the most appropriate single indicator of exposure. At high levels of exposure (total As excretion above 200 micrograms/l), As accumulates in the organism and DMAA excretion reflects its accumulation. At low levels of exposure (total As excretion below 50 micrograms/l) a short-term accumulation does not occur and the best biological indicator of exposure is InAs excretion. Seafood ingestion brings about a marked increase in urinary excretion of total As that lasts for 24-48 h and is not accompanied by any increase in InAs, MMAA or DMAA excretion. Organic As from seafood does not mix with the pool of inorganic As in the organism and may be separately detected in urine. In the biological monitoring of human exposure to As, particularly in the case of high urinary values, the speciation of the chemical forms of As in urine is necessary in order to establish with certainty the source, industrial or alimentary, of exposure.

Immune parameters in biological monitoring of pesticide exposure: current knowledge and perspectives

Exposure to pesticides can cause a number of effects on the immune system, varying from a slight modulation of immune functions to the development of clinical immune diseases. The aim of this study has been reviewing published data on immune effects of pesticides in humans, with particular attention for effects observed in absence of any other change, and to the possibility of identifying a dose effect relationship. Some evidence of immunotoxic effects in man involve organophosphorus compounds, some organochlorine insecticides (OC), some carbamates, some phenoxy herbicides, dithiocarbamates, and pentachlorophenol (PCP). The alterations are usually observed in absence of any other change; in some cases, data suggest the presence of a dose effect relationship. The prognostic significance of the observed changes is still unclear. The Authors propose a tier approach to assess immune effects in humans.

Allergens in indoor air: environmental assessment and health effects.

It has been suggested that the increase in morbidity and mortality for asthma and allergies, may also be due to an increase in exposure to allergens in the modern indoor environment. Indoor allergen exposure is recognised as the most important risk factor for asthma in children. House dust mites, pets, insects, plants, moulds and chemical agents in the indoor environment are important causes of allergic diseases. House dust mites and their debris and excrements that contain the allergens are normally found in the home in beds, mattresses, pillows, carpets and furniture stuffing, but they have also been found in office environments. Domestic animals such as cats, dogs, birds and rodents may cause allergic asthma and rhinoconjunctivitis. The exposure usually occurs in homes, but also in schools and kindergartens where domestic animals are kept as pets or for education; moreover, cat and dog owners can bring allergens to public areas in their clothes. Allergy to natural rubber latex has become an important occupational health concern in recent years, particularly among healthcare workers; when powdered gloves are worn or changed, latex particles get into the air and workers are exposed to latex aerosolised antigens. To assess the environmental risk to allergen exposure or to verify if there is a causal relationship between the immunologic findings in a patient and his/her environmental exposure, sampling from the suspected environment may be necessary.

Biological monitoring of human exposure to atrazine

Atrazine exposure was evaluated in six manufacturing workers by personal and biological monitoring. Total atrazine exposure varied from 10 to 700 mumol per workshift and total urinary atrazine excretion accounted for 1-2% of the external dose. The spectrum of the urinary atrazine metabolites comprises bi-dealkylated (80%), deisopropylated (10%), deethylated (8%) and unmodified atrazine (2%). The metabolites are eliminated in urine in slightly longer than 24 h: 50% of the amount is excreted in the first 8 h following the workshift.

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 (Spearmans rho=0.770 and 0.702, P=0.009 and 0.024, respectively). Wine consumption positively influenced the excretion of ETU.

Toxicological and immune findings in workers exposed to Pentachlorophenol (PCP)

Pentachlorophenol (PCP) is a pesticide used worldwide in industrial and domestic applications. Data available on the effects of technical-grade PCP on the immune system are insufficient and equivocal; some data indicate inhibitory effects, whereas others suggest stimulating effects. This study was performed to evaluate toxicological and immune findings in 32 subjects who had prolonged exposure to PCP in a wood factory and in 37 controls. PCP concentrations were determined in plasma and urine of all subjects. Lymphocyte subsets of CD3-, CD4-, and CD8-positive cells were evaluated, and the proliferative response of peripheral blood mononuclear cells (PBM) to mitogens was assessed. The results suggested the absence of major laboratory and clinical signs of PCP-dependent immune deficiency. A weak effect of long-term exposure to PCP on the functional immune response could not be ruled out because of the finding of a decreased response to 5% PHA in the high-exposure group. A weak effect against hepatocyte membrane was evidenced by the finding of raised serum concentration of glycocholic, taurodeoxycholic, and glycochenodeoxycholic acids in subjects directly exposed to PCP for more than 10 y.

Personal carbon monoxide exposure levels: contribution of local sources to exposures and microenvironment concentrations in Milan

In the framework of the EXPOLIS study in Milan, Italy, 48-h carbon monoxide (CO) exposures of 50 office workers were monitored over a 1-year period. In this work, the exposures were assessed for different averaging times and were compared with simultaneous ambient fixed-site concentrations. The effect of gas cooking and smoking and different methods of commuting on the microenvironment and exposure levels of CO were investigated. During the sampling the subjects completed a time–microenvironment–activity diary differentiating 11 microenvironments and three exposure influencing activities: gas cooking, smoking and commuting. After sampling, all exposure and time allocation data were stored in a relational database that is used in data analyses. Ambient 48-h and maximum 8-h distributions were similar compared to the respective personal exposures. The maximum 1-h personal exposures were much higher than the maximum 8-h exposures. The maximum 1-h exposures were as well higher than the corresponding ambient distribution. These findings indicate that high short-term exposures were not reflected in ambient monitoring data nor by long-term exposures. When gas cooking or smoking was present, the indoor levels at “home-” and in “other indoor” microenvironments were higher than without their presence. Compared with ambient data, the latter source was the most affective to increase the indoor levels. Exposure during commuting was higher than in all other microenvironments; the highest daily exposure contribution was found during “car/taxi” driving. Most of the CO exposure is acquired in indoor microenvironments. For the indoor microenvironments, ambient CO was the weakest predictor for “home indoor” concentrations, where the subjects spent most of their time, and the strongest for “other indoor” concentrations, where the smallest fraction of the time was spent. Of the main indoor sources, gas cooking, on average, significantly raised the indoor exposure concentrations for 45 min and tobacco smoking for 30 min. The highest exposure levels were experienced in street commuting. Personal exposures were well predicted, but 1-h maximum personal exposures were poorly predicted, by respective ambient air quality data. By the use of time–activity diaries, ETS exposure at the workplaces were probably misclassified due to differences in awareness to tobacco smoke between smokers and nonsmokers.

Assessment of human exposure to atrazine through the determination of free atrazine in urine

Studies on metabolism and excretion of atrazine in man are not available in the literature. The present study has investigated human exposure to atrazine during its industrial production by means of assessment of ambient exposure and determination of free atrazine in urine. Four workers exposed to atrazine during its manufacture and packaging in a production plant, volunteered for the study. Atrazine was determined in airborne dust of the working environment obtained by personal sampling, on skin pads according to the WHO standard method, and on the skin of the hands of the workers by means of a washing procedure. Urine was collected before, during, and after exposure. A 24 hr collection before the first workshift, all the urine voided during the monitoring period, subdivided in 8 hr fractions; and one or more 12 hr samples after the end of the exposure period were collected.