Pietro Sartorelli

Urinary excretion of alkylphosphates in the general population (Italy)

Xenobiotic residues and their metabolites in biological fluids of the general population are an important indicator of exposure to toxic substances dispersed in the environment. Urine samples collected from 124 subjects living in SW Tuscany, Italy were analyzed for alkylphosphates (dimethylphosphate, dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate, diethylthiophosphate, diethyldithiophosphate), aspecific metabolites of organophosphorus insecticides. The compound most frequently found was dimethylthiophosphate which was detectable in 99% of the subjects analyzed, with a geometric mean of 70.7 nmol/g creatinine. The other substances were found in the following percentages of our population, at the following mean concentrations: dimethylphosphate, 87%, 62.8 nmol/g creat.; dimethyldithiophosphate, 48%, 21.1 nmol/g creat.; diethylphosphate, 81%, 27.4 nmol/g creat.; diethylthiophosphate, 73%, 22.8 nmol/g creat.; diethyldithiophosphate, 7%, 13.7 nmol/g creatinine. Subjects eating food (fruit, meat, vegetables) that was not their own produce showed higher urinary concentrations of nearly all the compounds. The other variables considered (sex, age, residence, alcohol, smoking, sampling period) seem to affect the percentages of positive values of the various substances but to different degrees. Age and source of foods were the most important variables for dimethylthiophosphate excretion when mean values were analyzed by Students t-test and analysis of variance (ANOVA).

Biological monitoring of exposure to organophosphorus insecticides by assay of urinary alkyl phosphates: influence of protective measures during manual operations with treated plants

Biological monitoring was carried out by assaying urinary dimethylated alkylphosphates [dimethyldithiophosphate (DMDTP), dimethylthio-phosphate (DMTP), and dimethylphosphate (DMP)] in 11 workers exposed to chlorpyrifos-methyl and azinphosmethyl during operations in a previously sprayed peach orchard. The subjects were divided into groups on the basis of the protective clothing worn. The results were compared with those of a reference group of 99 subjects not occupationally exposed to organophosphorus insecticides. The hand-wash liquid of the workers was also analyzed to evaluate skin contamination. Significantly higher levels of urinary excretion of alkylphosphates were found in all groups than in unexposed controls (Students t test). A good correlation was found between quantities of the active ingredients on the hands and urinary excretion of total dimethylated alkylphosphates (r = 0.788) and of DMTP (r = 0.749) and DMP (r = 0.790) alone. The correlation between azinphos-methyl on the hands and urinary excretion of DMDTP was poor (r = 0.069). Under the working conditions investigated, the main route of absorption seems to be via the skin. Respiratory absorption, however, also appears significant in view of the difference in urinary excretion of dimethylated alkylphosphates found between subjects with and without face masks.

Prediction of percutaneous absorption from physicochemical data: A model based on data of in vitro experiments

Correlations between in vitro percutaneous absorption data and physicochemical properties of industrial chemicals are evaluated in order to develop predictive mathematical models based on said properties. Percutaneous diffusion of 16 pounds of occupational interest, eight of which were polycyclic aromatic hydrocarbons (acenaphthene, anthracene, benzo(a)anthracene, chrysene, phenanthrene, fluorene, naphthalene, pyrene), six organophosphorus insecticides (acephate, chlorpyrifos, dimethoate, fenitrothion, methamidophos, omethoate) and two phenoxycarboxylic herbicides (2,4-D, MCPA), were tested in vitro using monkey (Cercopithecus aetiops) skin. The test apparatus consisted of nine static diffusion cells with normal saline, gentamycin sulphate and 4% bovine serum albumin as receiving solution. Test compounds were applied at various concentrations in 30 microliters of acetone solution and determined, in the receiving phase, by chemical analysis. Values for ln Kow (octanol/water partition coefficient) were correlated with experimentally determined values of the permeability constant Kp (r = 0.90, P < 0.001) and lag time (r = 0.81, P < 0.01). Analysis of variance in a model of multiple linear regression between Kp, ln Kow and water solubility [water] of the compounds, showed that the data had a highly significant fit (P < 0.0001). A more general model which also included molecular weight (MW) and vapour pressure was evaluated as well, but the two variables made no substantial difference. Multiple regression analysis between lag time, ln Kow and [water] was significant (P < 0.0001), whereas introduction of vapour pressure and MW as independent variables did not significantly improve the predictive effect on lag time. Our experimental system, therefore, enables the values of Kp and lag time to be predicted with reasonable precision on the basis of ln Kow and [water] values, using the algorithm derived from the multiple linear regression equation.

Biological monitoring of exposure to chlorpyrifos-methyl by assay of urinary alkylphosphates and 3,5,6-trichloro-2-pyridinol.

The results of biological monitoring by assay of urinary 3,5,6-trichloro-2-pyridinol and alkylphosphates (DMP, DMTP) in groups of 9 and 2 workers exposed to chlorpyrifos-methyl during vine spraying and manual leaf thinning 5-11 d after spraying, respectively, are reported. The results are compared with those of a control group of 46 subjects not occupationally exposed to organophosphate insecticides. Significantly higher urinary excretion of metabolites (Mann-Whitney U-test) was found in both groups than in controls. Levels of 3,5,6-trichloro-2-pyridinol (mean +/- SD) were 15.9 + 10.6 nmol/g creatinine (n = 33) for controls, 92.4 + 162.5 nmol/g creatinine (n = 20) for manual workers, and 675.5 + 1110.8 nmol/g creatinine (n = 48) for workers spraying and mixing the insecticide. Levels of DMP (mean +/- SD) were 63.8 + 100.1 nmol/g creatinine (n = 42), 123.0 + 79.0 nmol/g creatinine (n = 20), and 577.2 + 1003.2 nmol/g creatinine (n = 61), respectively, for the same 3 groups. Levels of DMTP (mean +/- SD) were 153.4 + 164.4 nmol/g creatinine (n = 43), 489.3 + 288.3 nmol/g creatinine (n = 20), and 297.6 + 215.4 nmol/g creatinine (n = 61), respectively, for the same 3 groups. Good correlations were found between urinary excretion of 3,5,6-trichloro-2-pyridinol and DMP (r = .776 for manual workers; r = .775 for workers mixing and spraying the insecticide) or DMTP (r = .558 and r = .746, respectively for the same 2 groups). The peak of excretion of the three metabolites was found in urine samples collected the night after the spraying or leaf thinning operations.

In vitro percutaneous penetration of methyl-parathion from a commercial formulation through the human skin.

OBJECTIVE: To compare in vitro percutaneous absorption of methyl-parathion dissolved in an acetone vehicle and in the form of a commercial formulation. METHODS: Penetration through the human skin was measured in Franz diffusion cells with full thickness skin from a human cadaver as the membrane. The two tailed non-parametric Mann-Whitney U test was used to compare the cumulative diffusion of methyl-parathion in the receptor fluid of the cells at various time intervals. RESULTS: In vitro skin penetration of methyl-parathion was significantly higher with the commercial formulation. The percentage of the applied dose absorbed after 24 hours was 5.20% v 1.35%. The mean lag time was < 8 hours. CONCLUSION: Assessments of uptake and internal dose after exposure to pesticides should be based on the commercial products rather than active ingredients, because of the crucial role of the vehicle, as shown in this study.

Multiroute exposure assessment and excretion of urinary metabolites of fenitrothion during manual operations on treated ornamental plants in greenhouses.

Abstract. The results of environmental and biological (five subjects) monitoring of exposure to fenitrothion during manual operations on treated ornamental plants in greenhouses are reported. Urinary excretion [GM (GSD)] of alkylphosphates [dimethylphosphate (DMP) + dimethylthiophosphate (DMTP)] (nmol/g creat) was 244.8 (1.8), 174.0 (2.0), and 354.4 (1.6) respectively, on the first (Monday), third (Wednesday), and fifth (Friday) days of work. These levels were not significantly higher than those recorded in a control group (21 subjects) in which urinary excretion [GM (GSD)] of DMP + DMTP was 102.8 (4.2) nmol/g creat. Air concentrations of fenitrothion (nmol/m3) ranged from 45.5 to 81.2 on Monday, 17.3 to 27.1 on Wednesday, and 9.7 to 19.1 on Friday. Dose estimates showed that the respiratory-absorbed doses of fenitrothion accounted, on the average (GM), for 94.7%, 93.1%, and 91.5% of the total absorbed dose on Monday, Wednesday, and Friday, respectively. Multiple regression analysis showed a significant correlation (r2 = 0.595) between urinary excretion of DMP + DMTP, respiratory-absorbed dose, and skin-absorbed dose, estimated on Monday and Wednesday. Total estimated absorbed doses did not exceed the acceptable daily intake for fenitrothion. Serum and erythrocyte cholinesterase activities were not significantly different before and after exposure.

Asbestos exposure assessment by mineralogical analysis of bronchoalveolar lavage fluid.

Mineralogical analysis of bronchoalveolar lavage fluid (BALF) by electron microscopy can represent the most suitable method for assessing asbestos exposure. However, it has been claimed that no standardized or systematic approach to the subject of mineralogical analysis exists. This study aimed to evaluate BALF mineralogical analysis by transmission electron microscopy as biomarker of asbestos fiber load. BALF was examined in 108 exposed workers and 57 patients who underwent diagnostic fiberoptic bronchoscopy for various clinical purposes. Asbestos bodies in BALF were counted with a phase-contrast microscope. Fibers were counted and analyzed by transmission electron microscopy, which showed a significant difference between the two populations and positive results for all exposed subjects. Only 82.2% of the exposed population tested positive for asbestos bodies. Subjects with long-term exposure had higher concentrations of fibers than did those with more recent exposure, probably because of the higher workplace exposure levels in the past. The results of the study confirm that fiber concentration in BALF can be considered as a reliable biomarker of past asbestos exposure, even many years after the end of exposure.

The European Status Quo in legal recognition and patient-care services of occupational skin cancer

Skin cancer is the most common malignancy in Caucasian populations worldwide and ultraviolet radiation (UVR) is known for being the number one carcinogen. As, especially in outdoor workers, UVR is an inevitable carcinogen, the prevention and management of UVR‐related skin cancers in these at‐risk populations represent a collective challenge for dermatologists and healthcare policymakers likewise.

Serum erythropoietin and blood lead concentrations

The aim of the study was to test the hypothesis that high blood lead levels are associated with depressed serum erythropoietin concentrations in workers occupationally exposed to lead. The results in exposed workers and in a control group of unexposed subjects were compared. Blood lead values were ≤20 μg/dl in unexposed subjects and ≥30 μg/dl in exposed subjects. The two groups of exposed workers and the control population were matched for sex and age. Hemoglobin levels were not affected by blood lead values and did not differ significantly between the three groups. The two-tailed, nonparametric Mann-Whitney U-test was used to compare unpaired groups. The Spearman rank correlation test was used to evaluate the dose-effect relationship between Pb and EPO. The analysis of the data indicate that erythropoietin values are significantly lower in exposed subjects than in controls. However no correlation was demonstrated between blood lead concentrations and erythropoietin in any group.

Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from coal dust.

To understand the dermal uptake of chemicals bound to soil and dust, information on the neat substance is helpful but does not seem sufficient. Because of its content of polycyclic aromatic hydrocarbons (PAHs) coal is suspected to be carcinogenic. However, experimental carcinogenity studies on coal dust never succeeded in demonstrating a higher incidence of cancer in treated animals. The aim of the study was to assess dermal penetration through human skin of PAHs from coal dust. A sample of coal dust was grinded and sieved, using the particle size of <30 μm. An in vitro static diffusion cell system validated by in vitro/in vivo comparison has been used to study dermal penetration through human skin of PAHs from coal dust compared with their percutaneous absorption as pure compounds. No percutaneous penetration of PAHs was observed in the cells where coal dust was applied, while dermal penetration was demonstrated for PAHs applied in an acetone solution. Results agree with the literature that PAHs are poorly absorbed through the skin from solids. Dermal risk assessment of PAHs should take into account not only the degree and the extent of skin contamination, but also their bioavailability, which is heavily influenced by the physico-chemical characteristics of the matrix.