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Biomedical subjects

P Apostoli

Publications and source records attributed to P Apostoli.

At least 37 records · Page 2Linked to original sources
PubMed2000

Are current biomarkers suitable for the assessment of manganese exposure in individual workers?

BACKGROUND: Whole blood and urinary manganese have been measured in occupational and environmental studies for the assessment of exposure. The aim of this study was to assess the relationship between the airborne concentrations of manganese and these biological indicators. METHODS: Environmental and biological monitoring was performed in a group of 94 employees in a ferroalloy production, who were exposed to manganese (Mn) oxides (MnO(2) and Mn(3)O(4)). The results were compared with those from a control group of 87 subjects not exposed to Mn. RESULTS: Mn exposure levels ranged between 5 and 740 micrograms/m(3), with arithmetic and geometric mean and median values being 202.6, 97.6, and 150 micrograms/m(3), respectively. Arithmetic and geometric means for Mn in total blood (MnB) were, respectively, 10.3+/-3.8 and 9.7 micrograms/L in the exposed and 5.9+/-1.7 and 5.7 micrograms/L in the controls. For urinary Mn (MnU), arithmetic and geometric means were, respectively, 4.9+/-3.6 and 3. 8 micrograms/L in the exposed and 1.2+/-1.4 and 0.7 micrograms/L in the controls. On a group comparison, a significant relationship was found between high and low exposed subgroups, identified according to Mn atmospheric concentrations (MnA), for both MnB (F value=38.0, P > 0.0001) and MnU (F value=36.1, P > 0.0001). On a linear relationship, a correlation was observed between MnA and MnB (r=0. 34; r(2)=0.112; P=0.001), whereas no association was found between MnA and MnU. A significant relationship emerged also between MnB and MnU (r=0.48, r(2)=0.23, P < 0.0001). No association was observed between an index of cumulative exposure and the biological indicators of exposure. CONCLUSIONS: These results confirm that MnB and MnU can discriminate groups of occupationally exposed workers from groups of nonexposed subjects. MnB is also related to the intensity of external exposure on a linear relationship, but given a high variability, it is not suitable for individual biological monitoring. Therefore, further research should focus on more accurate biomarkers of Mn exposure.

Biomarkers↗
PubMed2000

The effect of lead on male fertility: a time to pregnancy (TTP) study.

BACKGROUND: Growing attention has been paid in recent decades to the effects on male reproduction of occupational exposures to toxic agents. There is strong evidence that high level exposure to lead, i. e. blood lead level (PbB) > 70 microg/dl, is associated with male infertility and some reports suggest an effect even at lower PbB (i. e. < 50 microg/dl). The aim of this study is to shed more light on the postulated association between occupational exposure to relatively low levels of inorganic lead and reduced fertility in men estimated by the length of time taken to conceive: time to pregnancy (TTP). METHODS: A survival analysis of TTP of the last pregnancy was performed adopting the Kaplan Meier methodology. The target population included 782 lead-exposed workers and 165 controls. 251 lead workers and 119 controls were finally eligible and interviewed. Lead-exposed subjects were distributed into four exposure levels according to their blood lead concentration (i.e. < 20; 20-29; 30-39, and >/= 40 microg/dl). The Cox model was adopted to estimate the Relative Risk of unsuccessful waiting time to pregnancy associated to the exposure to lead. RESULTS: A statistically significant difference in fecundability (shorter TTP) in favor of exposed subjects was detected. Nevertheless, longer TTP was associated within the exposed group to higher levels of PbB, even though the gradient is not statistically significant. The exposed workers revealed an average number of children larger than those not exposed, and a clear gradient of the same variable was evident from the lowest to the highest PbB level. Focusing on subjects with one child only, the Cox model confirmed no significant difference in fecundability between exposed and not exposed, whereas a statistically significant longer TTP was associated to the exposure level >/= 40 microg/dl. CONCLUSIONS: It is not easy to assert or to deny the effect of inorganic lead on male fecundity, quantitatively estimated by TTP, with the data available for this study. In fact, while the general data seem to exclude effects of Pb on male fecundability a more detailed analysis suggests an unfavorable effect at relatively high levels of exposure but some confounding attributable to personal and social conditions of the workers cannot be ruled out. Further investigations with a better control of confounding are needed.

Adult↗
PubMed2000

Effects of four inorganic lead compounds on the proliferation and junctional coupling of cultured REL liver cells.

BACKGROUND: Chronic, low-level exposure to inorganic lead (Pb) has been involved in a number of human diseases, including tumors. In this study, the effect of four different inorganic Pb compounds (acetate, chloride, monoxide, and sulfate) was evaluated, in vitro, on liver-derived REL cells, known to be very sensitive to tumor promoters. METHODS: Cytotoxicity and effects on intercellular communication (GJIC) were evaluated, respectively, by cell- density/proliferation and dye-transfer assays. Pb concentration in the media solutions used for each treatment was quantified by atomic absorption spectroscopy-electrothermal atomization. RESULTS: Each of the Pb compounds we tested showed a typical dose- and time-related effect on REL cell proliferation, this effect not being related to the free metal concentration. Contrary to classical tumor promoters, none of the compounds significantly affected REL GJIC (1-hour treatment). CONCLUSIONS: Our results are indicative of specificity in the effects of the different Pb compounds. The mechanism(s) of their action need further investigations.

Animals↗
PubMed1999

Biological monitoring of occupational exposure to inorganic arsenic.

OBJECTIVES: This study was undertaken to assess reliable biological indicators for monitoring the occupational exposure to inorganic arsenic (iAs), taking into account the possible confounding role of arsenicals present in food and of the element present in drinking water. METHODS: 51 Glass workers exposed to As trioxide were monitored by measuring dust in the breathing zone, with personal air samplers. Urine samples at the end of work shift were analysed for biological monitoring. A control group of 39 subjects not exposed to As, and eight volunteers who drank water containing about 45 micrograms/l iAs for a week were also considered. Plasma mass spectrometry (ICP-MS) was used for the analysis of total As in air and urine samples, whereas the urinary As species (trivalent, As3; pentavalent, As5; monomethyl arsonic acid, MMA; dimethyl arsinic acid, DMA; arsenobetaine, AsB) were measured by liquid chromatography coupled with plasma mass spectrometry (HPLC-MS) RESULTS: Environmental concentrations of As in air varied widely (mean 84 micrograms/m3, SD 61, median 40) and also the sum of urinary iAs MMA and DMA, varied among the groups of exposed subjects (mean 106 micrograms/l, SD 84, median 65). AsB was the most excreted species (34% of total As) followed by DMA (28%), MMA (26%), and As3 + As5 (12%). In the volunteers who drank As in the water the excretion of MMA and DMA increased (from a median of 0.5 to 5 micrograms/day for MMA and from 4 to 13 micrograms/day for DMA). The best correlations between As in air and its urinary species were found for total iAs and As3 + As5. CONCLUSIONS: To avoid the effect of As from sources other than occupation on urinary species of the element, in particular on DMA, it is proposed that urinary As3 + As5 may an indicator for monitoring the exposure to iAs. For concentrations of 10 micrograms/m3 the current environmental limit for iAs, the limit for urinary As3 + As5 was calculated to be around 5 micrograms/l, even if the wide variation of values needs critical evaluation and application of data. The choice of this indicator might be relevant also from a toxicological point of view. Trivalent arsenic is in fact the most active species and its measure in urine could be the best indicator of some critical effects of the element, such as cancer.

Adult↗
PubMed1999

Objectives, designs and populations of the European Asclepios study on occupational hazards to male reproductive capability.

The main objective of the Asclepios program was to examine occupational risk factors for the male reproductive system. The program focused on occupational exposure to fungicides (farmers, greenhouse workers, and vineyard workers), styrene (laminators in the reinforced plastics industry) and inorganic lead (battery workers, foundry workers, and lead smelters). Questionnaire studies of time to pregnancy were combined with longitudinal and cross-sectional studies of semen quality. The 8 data-collecting centers addressed 6553 male workers and contributed time-to-pregnancy values on the 3077 most recent pregnancies. Data collection was by interview or self-collection. The average response rate across all exposures and centers was 69.8%. The Asclepios project is the first international multicenter research project on environmental risks to male reproductive function. A protocol for epidemiologic research on occupational risk factors to the male reproductive system was developed, and links between epidemiologic and experimental units were established. The majority, but not all, of the studies was completed within the given time frame.

Adult↗
PubMed1998

Decreased drug accumulation and increased tolerance to DNA damage in tumor cells with a low level of cisplatin resistance.

In an attempt to examine the cellular changes associated with cisplatin resistance, we selected a cisplatin-resistant (A43 1/Pt) human cervix squamous cell carcinoma cell line following continuous in vitro drug exposure. The resistant subline was characterized by a 2.5-fold degree of resistance. In particular, we investigated the expression of cellular defence systems and other cellular factors probably involved in dealing with cisplatin-induced DNA damage. Resistant cells exhibited decreased platinum accumulation and reduced levels of DNA-bound platinum and interstrand cross-link frequency after short-term drug exposure. Analysis of the effect of cisplatin on cell cycle progression revealed a cisplatin-induced G2M arrest in sensitive and resistant cells. Interestingly, a slowdown in S-phase transit was found in A431/Pt cells. A comparison of the ability of sensitive and resistant cells to repair drug-induced DNA damage suggested that resistant cells were able to tolerate higher levels of cisplatin-induced DNA damage than their parental counterparts. Analysis of the expression of proteins involved in DNA mismatch repair showed a decreased level of MSH2 in resistant cells. Since MSH2 seems to be involved in recognition of drug-induced DNA damage, this change may account for the increased tolerance to DNA damage observed in the resistant subline. In conclusion, the involvement of accumulation defects and the increased tolerance to cisplatin-induced DNA damage in these cisplatin-resistant cells support the notion that multiple changes contribute to confer a low level of cisplatin resistance.

Antineoplastic Agents↗
PubMed1998

Significance and utility of reference values in occupational medicine.

Although it is generally accepted that reference values can be included among the instruments of modern occupational medicine, problems arise when applying them from clinical chemistry to the needs of occupational medicine. Here some general aspects regarding reference values beginning from their theoretical basis, their significance and importance and their possible use in occupational medicine are reviewed. Furthermore, their relationship with other more familiar 'guideline values', such as action levels and limit values, is demonstrated.

Guidelines as Topic↗
PubMed1998

Application of high performance liquid chromatography/tandem mass spectrometry in the environmental and biological monitoring of health care personnel occupationally exposed to cyclophosphamide and ifosfamide.

Twenty four workers (10 involved in the preparation and 14 in administration) exposed to cyclophosphamide (CP) and ifosfamide (IF) in two Italian hospitals were monitored. The extent of exposure was assessed by the analysis of air samples, wipe samples, pads and gloves. Urinary excretion at the beginning and at the end of the work shift was also measured by liquid-liquid extraction and analysis by high performance liquid chromatography/tandem mass spectrometry. Three out of 24 air samples were positive for CP or IF. In wipe samples, CP concentrations ranging from < 0.001 to 82.4 micrograms/dm2 in Hospital A (32 samples) and from 0.2 to 383.3 micrograms/dm2 in Hospital B (17 samples), were found. IF concentrations varied from < 0.001 to 90.9 micrograms/dm2 in Hospital A and from 0.01 to 141.5 micrograms/dm2 in Hospital B. Pads (from 11 to 13 for each operator) were contaminated with CP and IF especially on arms, legs and chest. The use of a plastic-backed liner on the working tray in the laminar flow hoods was demonstrated to compromise the containment properties of the hood. Urine samples were positive for CP in 50% of the workers (range: 0.1-2.1 micrograms/L), whereas IF was detected in 2 subjects only (range: 0.1-0.8 microgram/L). The results of this investigation demonstrate that vertical laminar airflow hoods, when incorrectly used, might represent a source of contamination and that higher risk may depend on lack of educational programmes and observance of preventive guidelines.

Air↗
PubMed1998

Multiple exposure to arsenic, antimony, and other elements in art glass manufacturing.

Art glass manufacturing is one of the most interesting examples of exposure to complex mixtures. Among the raw materials used are silica sand, borax, carbonates, nitrates of Ca, Na, K, and a great number of compounds that are mainly oxides of As, Sb, Al, Zn, Cr, Ni, Sn, Se, Cd, Mn, Cu, Co, Fe, Nd, Er, Eu, and La. In six art glass factories that use As or Sb as fining agents, the exposure to these elements was investigated in 32 workers by means of environmental and biological monitoring. Analysis was conducted by atomic absorption spectrometry (AAS) and inductively coupled plasma mass spectrometry (ICP-MS). The results confirmed that As, which is the main carcinogen in glass production, reaches high air concentrations and is generally above the American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value-time-weighted average (TLV-TWA) of 10 micrograms/m3. When partly substituted by antimonial compounds, As air concentrations dropped dramatically, while the air levels of Sb (which is considered less toxic but is classified as a class 2B carcinogen by IARC) were relatively low and below the ACGIH TLV-TWA of 500 micrograms/m3. Exposure to As and Sb also differed in the three types of jobs investigated: As was high in oven chargers, Sb was higher in batch mixers, and both elements were low in makers-formers. Eleven to 18 elements were detected: arsenic, Al, Ba, Sb, Pb, and Zn were the elements most frequently measured (in tens, and in some cases hundreds, of micrograms/m3), followed by B, Li, Mn, Se, Sn, Sr, Ce, La, and Nd (in micrograms or in some cases tens of micrograms/m3. The results of biological monitoring for As, Sb, and other elements were in agreement with environmental monitoring data. We concluded that multiple detection of elements is a useful tool (or the evaluation of exposure to complex mixtures such as those used in the art glass industry and that such detection also allows a more accurate evaluation of related epidemiological data.

Antimony↗
PubMed1998

Arsenobetaine is not a major metabolite of arsine gas in the rat.

Many organisms can easily dispose of toxic inorganic arsenic species through gradual methylation of the element and further urinary excretion. In order to clarify the urinary excretion of arsenobetaine observed in a human case of intoxication by arsine, the capacity of highly methylated arsenical synthesis has been investigated in rats acutely exposed during 1 h to increasing concentrations of the same gas [4 to 80 mg AsH3/m3]. Urinary metabolites of arsenic were determined with good agreement in two (Belgian and Italian) laboratories using two different analytical procedures. The sum of inorganic, mono- and dimethylated metabolites of arsenic in urine was shown to be related to the intensity of exposure to arsine. A biphasic relationship was observed: 1 h exposure to > 60 mg AsH3/m3 led to metabolite excretion which is roughly 10 times higher than for exposure levels below that limit, suggesting the saturation of a binding site reserve and the availability for metabolism of a greater proportion of the As absorbed above this threshold. Arsenobetaine production, if any, could only be detected when its presence in food was excluded; in addition, amounts appeared negligible and could be disregarded as a common arsenic metabolite in rats.

Air Pollutants, Occupational↗
PubMed1998

Determination of urinary 2,5-hexanedione in the general Italian population.

OBJECTIVE: Determination of the urinary levels of 2.5-hexanedione (2,5-HD) was performed in subjects belonging to the Italian general population to define the reference value for this metabolite. MATERIALS AND METHODS: Urine samples were collected from 123 healthy Italian subjects who had not been occupationally exposed to n-hexane or methyl-n-butyl ketone (60 men and 63 women; 53 living in urban areas and 70 living in rural areas; 36 smokers and 87 nonsmokers; 65 aged above 35 years and 58 aged below 35 years). The determinations were performed by a gas chromatography method using a flame ionization detector (FID). A quality-control step was realized by analysis of 78 of these samples by high-performance liquid chromatography (HPLC) with UV detection. RESULTS AND DISCUSSION: The distribution of 2,5-HD concentration was log-normal and the corresponding centiles at the 95% confidence interval were as follows: the 50th centile, 0.270 mg/l for men and 0.191 mg/l for women; the 75th centile, 0.352 and 0.330 mg/l, respectively, for men and women; and the 95th centile, 0.762 and 0.582 mg/l, respectively, for men and women. The reference value, calculated as the upper unilateral 95% tolerance interval at 95% of confidence, was 0.795 mg/l for men and 0.627 for women.

Adult↗
PubMed1998

Metabolic interferences in subjects occupationally exposed to binary styrene-acetone mixtures.

OBJECTIVE: To investigate the excretion of styrene metabolites (mandelic acid, MA, and phenylglyoxylic acid, PGA) in workers employed in plastic manufacturing to verify the possible influence of coexposure to acetone on styrene metabolism. METHODS: This study was carried out on 50 workers employed in 3 factories producing polyester buttons. The workers were divided into three groups according to three different levels of acetone exposure. The trend of excretion for metabolites was examined during and after work shifts. Styrene and acetone were monitored on Thursday during the entire work shift by passive dosimeters placed on the lapel of the workers' uniforms, desorbed by carbon disulfide, and analyzed by gas chromatography. Biological monitoring was performed by determination of the urinary metabolites of styrene in urine samples collected on Thursday at the middle and the end of the work shift. MA and PGA were determined by a high-pressure liquid chromatographic method. RESULTS: The styrene concentrations ranged between 16 and 439 mg/m3, and in ten samples they exceeded the TLV-TWA (213 mg/m3). The acetone concentration ranged between 15 and 700 mg/m3 (TLV-TWA 1780 mg/m3), with the mean value being 208 mg/m3. During cleaning operations higher exposures to acetone demonstrated, with concentrations ranging between 500 and 3400 mg/m3. The amounts of MA and PGA determined at the end of workshifts did not significantly differ between the groups with different levels of acetone coexposure. Analysis of variance (ANOVA) between the groups confirmed that MA and PGA excretion did not significantly differ, although the metabolite values measured on the "morning of the day after" appeared higher in those groups with high levels of acetone exposure and were related to the average airborne concentrations of the solvent. In addition, the range and degree of correlation between styrene in air and biological levels of metabolites were modified by coexposure to acetone. CONCLUSIONS: Our data demonstrate that amounts of MA and PGA did not differ in groups with different levels of acetone exposure, but when the acetone air concentration increased the degree of correlation between styrene and MA and PGA decreased. Furthermore, coexposure to acetone levels similar to those described herein may hamper the use of urinary metabolites for the assessment of exposure to styrene, especially on an individual basis.

Acetone↗