Biologic monitoring of exposure to organophosphorus pesticides in 195 Italian children.

One hundred ninety-five 6- to 7-year-old children who lived in the municipality of Siena (Tuscany, Italy), underwent biologic monitoring to evaluate urinary excretion of several alkylphosphates that are metabolites of organophosphorus pesticides. We evaluated dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP), and diethyldithiophosphate (DEDTP). We obtained urine samples taken in the children's schools, and each sample was accompanied by a questionnaire about lifestyle and dietary habits. We found DMP and DMTP in detectable concentrations in the greatest number of samples (96 and 94%, respectively). The DMP values were geometric mean (GM) 116.7, [geometric standard deviation (GSD) 2.5], and a range of 7.4-1,471.5 nmol/g creatinine. The corresponding DMTP values were GM 104.3 (GSD 2.8) and a range of 4.0-1,526.0 nmol/g creatinine. DMDTP, DEP, DETP, and DEDTP concentrations were GM 14.1, (GSD 3.0), and a range of 3.3-754.6 nmol/g creatinine in 34% of the children; GM 33.2, (GSD 2.4), and a range of 5.1-360.1 nmol/g creatinine in 75% of the children; GM 16.0, (GSD 2.9), and a range of 3.1-284.7 in 48% of the children; and GM 7.7, (GSD 2.1), and a range of 2.3-140.1 in 12% of the children, respectively. The significant variable for urinary excretion of these metabolites in children was pest control operations performed inside or outside the house in the preceding month; however, the presence of a vegetable garden near the house rarely emerged. The urinary excretion of alkylphosphates in children was significantly higher than in a group of the adult population resident in the same province.

Dermal exposure assessment of polycyclic aromatic hydrocarbons: in vitro percutaneous penetration from lubricating oil.

OBJECTIVES: Percutaneous penetration of polycyclic aromatic hydrocarbons (PAHs) is affected by various factors connected to exposure conditions. The nature of the matrix, such as that of oil, can strongly affect their percutaneous penetration. Risk assessment should consider these effects. We examined the effect of matrix on percutaneous penetration of PAHs, particularly that of lubricating oil. METHODS: The test apparatus consisted of an in vitro static diffusion cell system using full-thickness monkey (Cercopithecus aetiops) skin as the membrane and saline solution with gentamycin sulfate and 4% bovine serum albumin as receptor fluid. Chemical analysis of PAHs in the samples obtained from cells was carried out by inverse-phase HPCL, and the results were read by spectrofluorimetry. RESULTS: Comparing the penetration of 13 PAHs from a lubricating oil and from acetone solution with artificial sweat resulted in a significantly slower passage from the oil matrix for acenaphthene, anthracene, phenanthrene, fluoranthene, naphthalene, pyrene, fluorene (Mann-Whitney U test, P < 0.05). No significant differences in the passage were found for chrysene because, in the test with oil, its concentration was very often below the detection limit. For benzo[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, and benzo[a]pyrene it was possible to demonstrate a passage through the skin only when compounds were applied in acetone solution with artificial sweat. CONCLUSIONS: The results of the study suggest the necessity of dermal penetration data relevant for risk assessment, obtained under experimental conditions similar to the real exposure conditions.

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.

[Non-bioavailability of carcinogenic polycyclic aromatic hydrocarbons contained in coal dust]. / Sulla non biodisponibilità degli idrocarburi policiclici aromatici cancerogeni contenuti nella polvere di carbone.

The aim of the study was to ascertain whether polycyclic aromatic hydrocarbons (PAHs) especially 3,4-benzo(a)pyrene, could be eluted from coal dust that comes into contact with biological fluids or crosses the skin barrier. A fine-grained coal dust with known PAH content was placed into contact with homogenized pig lung or human gastric juices, and also applied to monkey skin, using the cutaneous window method. The results demonstrate that, in the in vitro systems used, PAHs contained in coal dust are not eluted by lung homogenate or gastric juices, nor are they capable of crossing the skin barrier. These results justify and support the interpretation given to the results of experimental carcinogenicity studies on coal dust which never succeeded in demonstrating a higher incidence of cancer, particularly lung cancer, in treated animals.

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.

[Percutaneous absorption of phenanthrene: an in vitro study of the monkey skin]. / Assorbimento percutaneo del fenantrene: studio in vitro su cute di scimmia.

It is well known that polycyclic aromatic hydrocarbons (PAHs) are absorbed through the skin of experimental animals and humans. However dermal uptake of PAHs is difficult to assess due to the lack of specific studies. The aim of this study was to obtain in vitro percutaneous absorption data for phenanthrene. In vitro penetration was measured with excised monkey (Cercopithecus Aethiops) skin in Franz diffusion cells, using a saline solution with 4% bovine serum albumin and gentamicin sulfate as receptor fluid. In two different groups of 7 and 2 cells, 38.1 and 95.3 nmol/cm2 respectively of phenanthrene were applied in an acetone vehicle. The absorption rate in the first group of 7 cells was 0.025 nmol/cm2/h (S.D. = 0.012), the lag time 11.7 (S.D. = 7.0) h and the breakthrough time 70 m (S.D. = 55 m). In the second group of 2 cells, the average absorption rate was 0.066 nmol/cm2/h and the average lag time 11.8 h. The percutaneous absorption at 24, 48 and 72 hours in the 7 cell group was 0.72% (S.D. = 0.52), 2.51% (S.D. = 1.76) and 3.9% (S.D. = 2.0) of the applied dose respectively. In the 2-cell group 1.1%, 2.78% and 4.5% of the applied dose was absorbed at 24, 48 and 72 hours. The results of the present study confirm the extent of percutaneous absorption of phenanthrene. The data can be compared with dermal absorption values of other PAHs obtained under the same experimental conditions.

[General anesthesia without nitrogen monoxide. Its use in abdominal surgery]. / Anestesia generale senza protossido d'azoto. Impiego in chirurgia addominale.

In view of the problems relating to the routine use of nitrogen monoxide in general anesthesia, the authors drew up an anesthesiological protocol excluding the use of N2O and replacing its analgesic effect with higher doses of fentanyl and a higher inspired percentage of isoflurane. Twenty-three patients due to undergo abdominal surgery were included in the study. The established anesthetic protocol was evaluated by the constant measurement of PAOS/D and heart rate, as well as lacrimation and sweating. Satisfactory results were achieved using this protocol in almost all patients, although further modifications to the protocol are planned to make the technique more stable and manageable.

[Subarachnoid anesthesia and peridural anesthesia: which are the causes of total failure? A clinical case]. / Anestesia sub-aracnoidea e anestesia peridurale: quali le cause di un completo insuccesso? Caso clinico.

The paper reports the case of patient undergoing cystoscopy and subsequently radical cystectomy suffering from BPCO and pulmonary emphysema who received sub-arachnoid anesthesia during the first operation and peridural anesthesia during the second, with total failure both times. The techniques were correctly performed and on both occasions it was necessary to resort to general anesthesia in order to perform the operation.

Atherosclerosis and aging. A morphometric study on arterial lesions of elderly and very elderly necropsy subjects.

A histomorphometric study was performed on arterial wall lesions of different arterial regions (arch, thoracic, abdominal parts of the aorta; right and left common and internal carotid arteries; coronary arteries; and basilar and middle cerebral arteries), collected from 108 elderly and very elderly (greater than 90 years of age) subjects who underwent necropsy. Lumen stenosis percentage, mean intimal thickening, and mean thickness of the media were measured by means of a computerized system using a manual input and graphic printout; statistical tests were performed using variance and regression analysis. Results showed that the arterial wall lesions in patients over 60 years of age tend to be stabilized in all regions studied except for the cerebral region, where the lesions tend to have a continuous progression related to age, even in a group of subjects over 90 years of age.

Delayed intimal lesion development in cerebral arteries versus aortic and carotid arteries of spontaneously hypertensive rats.

The development of intimal lesions is delayed in spontaneously hypertensive rats (SHR) in cerebral versus aortic and carotid arteries. The reason for this delayed involvement needs further study.

Delayed development of intimal lesions in cerebral arteries of spontaneously hypertensive rats subjected to a short-term atherogenic diet (TEM observations).

In adult spontaneously hypertensive rats, subjected to an atherogenic diet (2% cholic acid in a 5% hypercholesterolic diet) for 19 weeks both aortic and carotid artery lesions were already detectable on TEM examination while the cerebral arteries did not show any lesions. Similar findings have been previously obtained in rabbits and in monkeys on atherogenic diets.