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Biomedical subjects

R P Bos

Publications and source records attributed to R P Bos.

At least 19 recordsLinked to original sources
PubMed2003

Exposure to dust and particle-associated 1-nitropyrene of drivers of diesel-powered equipment in underground mining.

A field study was conducted in two mines in order to determine the most suitable strategy for ambient exposure assessment in the framework of a European study aimed at validation of biological monitoring approaches for diesel exhaust (BIOMODEM). Exposure to dust and particle-associated 1-nitropyrene (1-NP) was studied in 20 miners of black coal by the long wall method (Czech Republic) and in 20 workers in oil shale mining by the room and pillar method (Estonia). The study in the oil shale mine was extended to include 100 workers in a second phase (main study). In each mine half of the study population worked underground as drivers of diesel-powered trains (black coal) and excavators (oil shale). The other half consisted of workers occupied in various non-diesel production assignments. Exposure to diesel exhaust was studied by measurement of inhalable and respirable dust at fixed locations and by personal air sampling of respirable dust. The ratio of geometric mean inhalable to respirable dust concentration was approximately two to one. The underground/surface ratio of respirable dust concentrations measured at fixed locations and in the breathing zones of the workers was 2-fold or greater. Respirable dust was 2- to 3-fold higher in the breathing zone than at fixed sampling locations. The 1-NP content in these dust fractions was determined by gas chromatography-mass spectrometry/mass spectrometry and ranged from 0.003 to 42.2 ng/m(3) in the breathing zones of the workers. In mine dust no 1-NP was detected. In both mines 1-NP was observed to be primarily associated with respirable particles. The 1-NP concentrations were also higher underground than on the surface (2- to 3-fold in the coal mine and 10-fold or more in the oil shale mine). Concentrations of 1-NP in the breathing zones were also higher than at fixed sites (2.5-fold in the coal mine and 10-fold in the oil shale mine). For individual exposure assessment personal air sampling is preferred over air sampling at fixed sites. This study also suggests that particle-associated 1-NP much better reflects the ambient exposure to diesel exhaust particles than dust concentrations. Therefore, measurement of particle-associated 1-NP is preferred over measurement of dust concentrations by gravimetry, when linking ambient exposure to biomonitoring outcomes such as protein and DNA adducts and excretion of urinary metabolites of genotoxic substances.

Air Pollutants, Occupational↗
PubMed2003

Exposure related mutagens in urine of rubber workers associated with inhalable particulate and dermal exposure.

AIMS: To determine the relation of the inhalation and dermal exposure routes and mutagenic activity in the urine of rubber workers (n = 105). METHODS: Mutagenic activity of ambient total suspended particulate matter (TSPM), surface contamination wipes, and Sunday and weekday urine samples was assessed with S typhimurium YG1041 in the presence of a metabolic activation system. Each subject was grouped into one of two exposure categories for dermal exposure (high (>/=25 revertants/cm(2)), low (<25 revertants/cm(2))) based on the mutagenic activity detected on likely skin contact surfaces and into two airborne mutagenic exposure categories (high (>/=210 revertants/m(3)), low (<210 revertants/m(3))). The potential influence of skin aberrations and acetylation status (NAT2) on urinary mutagenicity levels was also evaluated. RESULTS: A non-significant increase of +1605 revertants/g creatinine in urinary mutagenicity during the workweek relative to levels observed on Sunday was observed for the total population. Subsequent multivariate regression analyses, with the subjects' weekday urinary mutagenicity levels as the dependent variable, revealed associations with environmental and mainstream tobacco smoke exposure, with the level of mutagenic contamination on surfaces with which the subjects had likely contact, with the subjects' inhalable particulate exposure level, with observed mild skin aberrations, and when the subjects had a slow acetylation phenotype. Similar associations, although weaker were observed with Sunday urinary mutagenicity levels as well, except for the association with slow acetylation phenotype. Based on measured exposure levels it could be estimated that a high potential for exposure to surface contamination with mutagenic activity increased weekday urinary mutagenicity by about 62% when compared to low exposed workers, while high inhalable particulate exposure levels increased weekday urinary mutagenicity levels by about 21%. Subjects with mild skin aberrations had an additional, non-significant, increase in weekday urinary mutagenic activity compared to subjects without any skin aberrations. DISCUSSION: Results suggest that the dermal exposure route may contribute more to the level of genotoxic compounds in urine of rubber workers than the inhalation route. Although the study was limited in size, the results warrant further investigation in the importance of and ways to effectively control the dermal exposure route in the rubber industry.

Acetylation↗
PubMed2002

BIOMarkers for occupational diesel exhaust exposure monitoring (BIOMODEM)--a study in underground mining.

Methods for the assessment of exposures to diesel exhaust were evaluated, including various biomarkers of internal exposure and early biological effects. The impact of possible biomarkers of susceptibility was also explored. Underground workers (drivers of diesel-powered excavators) at an oil shale mine in Estonia were compared with surface workers. Personal exposures to particle-associated 1-nitropyrene (NP) were some eight times higher underground than on the surface. Underground miners were also occupationally exposed to benzene and polycyclic aromatic hydrocarbons, as indicated by excretion of urinary metabolites of benzene and pyrene. In addition, increased O(6)-alkylguanine DNA adducts were detected in the white blood cells of underground workers, suggesting higher exposure to nitroso-compounds. However, no differences between underground and surface workers were observed in the levels of other bulky DNA adducts determined by 32P-postlabelling, or in DNA damage. The study indicated that smoking, diet and residential indoor air pollution are important non-occupational factors to consider when interpreting biomonitoring results.

Adult↗
PubMed2002

Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations.

To estimate the genotoxic risk of occupational exposure to antineoplastic drugs, chromosomal aberration (CAs) frequencies in peripheral lymphocytes were determined for 20 nurses handling antineoplastics and 18 referents matched for age and sex. Urinary cyclophosphamide (CP) excretion rates, which are used as a marker for drug handling, were also measured on these nurses. We have observed significant frequencies of CAs (about 2.5-fold increase) including chromatid breaks, gaps, and acentric fragments for nurses handling antineoplastics as compared to control subjects (p < 0.05, p < 0.01, excluding and including gaps, respectively). The mean value of CP excretion rate for 12 nurses was 1.63 microg/24 h, suggesting that when the nurses handled CP (and other antineoplastic drugs) this particular compound was absorbed. Our study has shown that increased genetic damage was evident in nurses, at population level, due to occupational exposure to antineoplastics. Until the effects of handling antineoplastics from low-level exposure are known, it will be important to keep the exposure to a minimum.

Adult↗
PubMed2001

Mutagenic exposure in the rubber manufacturing industry: an industry wide survey.

Mutagenic exposure conditions in several rubber manufacturing companies (n=9) in The Netherlands were studied. Mutagenicity of total suspended particulate matter in air (TSPM) and of wipe samples from possible contact surfaces were measured in the Ames mutagenicity assay with Salmonella typhimurium YG1041 in the presence of a metabolic activation system. Large differences in median mutagenicity of TSPM samples were observed between companies (range 49-1056rev/m(3)) and to a lesser extent between production functions (range 129-402rev/m(3)). The production function curing revealed overall the highest TSPM mutagenicity levels. Forty-one percent of the surface wipe samples revealed mutagenic activity ranging from 26 to 665rev/cm(2). Mixing had the largest proportion of positive samples resulting in a median surface mutagenic contamination of 39rev/cm(2). Surface mutagenic contamination, averaged per department/company combination, showed only a weak correlation with TSPM mutagenicity (r=0.28, P=0.05). Company, production function and total soluble matter (e.g. mass collected upon extraction with organic solvents with different polarity) explained 79 and 81% of the variability in mutagenicity of TSPM and surface contamination levels, respectively. "Company" was identified as the most important exposure determinant for mutagenic activity in TSPM and surface wipe samples. This indicates the importance of company specific determinants like production volume and rubber chemicals used for the encountered mutagenic exposure conditions. Detection of substantial mutagenic activity on possible contact surfaces supports furthermore the potential importance of the dermal route in the uptake of genotoxic compounds of workers in the rubber manufacturing industry.

Air Pollutants, Occupational↗
PubMed2000

Mutagenic profile of rubber dust and fume exposure in two rubber tire companies.

The aim of this study was to evaluate current mutagenic activity of ambient rubber dust and fume exposure in the mixing and curing departments of two rubber tire companies situated in The Netherlands and Sweden. Salmonella typhimurium strains YG1021, YG1024 and YG1041 were used to study the possible presence of mutagenic nitroarenes and aromatic amines. A large difference in mutagenic activity was found between the two companies. While the rubber tire company situated in The Netherlands revealed overall high mutagenic activity of rubber dust and fumes in the mixing and curing departments, respectively, 430 and 279 rev/m(3) (YG1041), the Swedish company showed almost no mutagenic activity, respectively, 18 and 54 rev/m(3) (YG1041). Further identification of the mutagenic profile showed that mutagenic activity was exclusively observed in S. typhimurium strains with elevated levels of O-acetyltransferase activity (YG1041 and YG1024) in the presence of a metabolic active liver S9 fraction, possibly indicating the presence of indirect mutagenic aromatic amines. These results show that although production processes and lay-out within rubber tire companies are comparable, differences in rubber chemicals used and overall level of control measures (e.g., good housekeeping, cleanliness) are likely to result in substantial differences in mutagenic exposure levels between companies.

Acetyltransferases↗
PubMed2000

[Lavage almost never indicated after an autointoxication].

In many Dutch hospitals gastric lavage leaving charcoal and a laxative is the treatment of choice after autointoxication. Gastric lavage is not without risks. No difference has been demonstrated in efficacy and safety of gastric lavage combined with administration of activated charcoal on the one hand and just administration of activated charcoal on the other. In theory, gastric lavage might be useful in patients presenting shortly after the selfpoisoning (up to 2 hours) and in the case of delayed gastric emptying up to 4 hours. Gastric lavage is indicated without doubt in patients presenting shortly after ingestion of toxic substances which are poorly adsorbed by charcoal (for instance lithium). In case of a mild intoxication (for example with benzodiazepines), the risks of drug toxicity do not outweigh those of lavage, regardless of the time elapsed after ingestion. If gastric lavage is applied, it should be performed properly, i.e. with warm water (38 degrees C), with a 36-40 Fr. tube, using aliquots of 200-300 ml. In a minority of the intoxications whole bowel lavage should be employed.

Charcoal↗
PubMed2000

Identification of dermal exposure pathways in the rubber manufacturing industry.

Current existing dermal exposure assessment strategies are predominantly based on regulatory protocols. In order to develop effective and efficient strategies more data driven approaches are needed. In a recently developed conceptual model for dermal exposure, compartments, barriers and mass transport processes relevant for dermal exposure were described. We systematically applied this conceptual model to the rubber manufacturing industry to assess dermal exposure to cyclohexane soluble matter (CSM) and used quantitative data to design an exposure assessment strategy. Identification of the spatial distribution of the dermal contamination showed high CSM surface concentrations for the upper body. Moreover, because of the high correlation between dermal exposure at the wrist and calculated total body exposure (r=0.89, P<0.01) an exposure assessment strategy based on only one pad sampler was employed to estimate CSM surface concentrations in the skin contaminant layer. Qualitative and quantitative evaluation of the relevant compartments and related mass transport processes demonstrated the importance of deposition of airborne contaminants and direct transfer of contaminants from sources and surfaces to the skin contaminant layer. Interestingly, the importance of the different exposure pathways varied considerably between production functions. The use of a model driven exposure assessment strategy in the rubber manufacturing industry revealed relevant skin regions, compartments and mass transport processes and enabled development of an effective and efficient strategy for dermal exposure assessment and hazard control in this particular occupational setting.

Bias↗
PubMed2000

Weekly patterns in smoking habits and influence on urinary cotinine and mutagenicity levels: confounding effect of nonsmoking policies in the workplace.

Lifestyle factors such as smoking have been shown to influence urinary mutagenicity. Therefore, these factors have to be considered carefully when evaluating occupational genotoxic exposures. We investigated day-to-day variability in active and passive tobacco smoke exposure by studying urinary cotinine levels and determined their influence on observed urinary mutagenicity. Urinary cotinine was assessed for 105 subjects employed in the rubber manufacturing industry in the Netherlands on Sunday, Wednesday, and Thursday. Urinary mutagenicity was measured by the Salmonella typhimurium strain YG1041 with metabolic activation for the Sunday urine sample and a pooled weekday urine sample. A sharp decrease in urinary cotinine concentration was observed during the week compared to Sunday for smokers (39%; P < 0.01) and nonsmokers (23%). Different smoking habits on Sunday resulted in higher regression coefficients for categorical proxies for smoking habits and urinary mutagenicity levels. However, regression coefficients for urinary cotinine and urinary mutagenicity were similar for the Sunday and weekday urine samples (beta = 0.29 and beta = 0.28, respectively). Consequently, these estimates were used to adjust urinary mutagenicity for tobacco smoke intake. Cotinine-adjusted urinary mutagenicity levels were comparable between smokers and nonsmokers, and a similar increase in urinary mutagenicity of 39% and 34%, respectively, was observed for both smokers and nonsmokers due to occupational genotoxic exposures or other changes in lifestyle factors. These results indicate that the introduction of nonsmoking policies in the workplace has reduced exposure to mainstream and environmental tobacco smoke, resulting in a temporal variation in lifestyle-related mutagenicity. Therefore, adequate adjustment for daily tobacco smoke exposure is a necessity when using the urinary mutagenicity assay to evaluate possible genotoxic exposures in the workplace.

Adult↗
PubMed1999

Urinary cyclophosphamide excretion and micronuclei frequencies in peripheral lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics.

In this study, urinary cyclophosphamide (CP) excretion rate, as well as micronuclei (MN) in peripheral lymphocytes and in buccal epithelial cells were determined for 26 nurses handling antineoplastics and 14 referents matched for age and sex. In urine samples of 20 out of 25 exposed nurses CP excretion rate was found in a range of 0.02-9.14 microg CP/24 h. Our results of the analyses of CP in urine demonstrates that when the nurses were handling CP (and other antineoplastic drugs) this particular compound was observed in urine. The mean values (+/-SD) of MN frequencies (%) in peripheral lymphocytes from the nurses and controls were 0.61 (+/-0. 32) and 0.28 (+/-0.16), respectively (p<0.01). The mean value (+/-SD) of MN frequency (%) in buccal epithelial cells of nurses was 0.16 (+/-0.19) and also mean MN frequency in buccal epithelial cells for controls was found to be as 0.08 (+/-0.08), (p>0.05). Age, sex and smoking habits have not influenced the parameters analyzed in this study. Handling time of antineoplastics, use of protective equipment and handling frequency of drugs have no effect on urinary and cytogenetic parameters analyzed. No correlation was found between the urinary CP excretion and the cytogenetic findings in nurses. Neither could we find any relationship between two cytogenetic endpoints. Our results have identified the possible genotoxic damage of oncology nurses related to occupational exposure to at least one antineoplastic agent, which is used as a marker for drug handling. As a whole, there is concern that the present handling practices of antineoplastic drugs used in the several hospitals in Ankara will not be sufficient to prevent exposure.

Adult↗
PubMed1999

Biological fate of [14C]-1-nitropyrene in rats following intragastric administration.

1-Nitropyrene (1-NP), a weak carcinogen associated with diesel exhaust particles, has previously been detected in workplace atmospheres with in-use diesel engines and in the general environment. In order to gain insight in its biological fate, a single dose of [14C]-1-NP (27.6 microCi, 750 mg/kg body weight, b.w.) was administered intragastrically to rats and the presence of metabolites in blood and tissue homogenates, and radioactivity associated with blood proteins and tissue DNA, were studied. Early peak levels of radioactivity observed in blood and tissue homogenates indicated a rapid absorption of [14C]-1-NP from the gastrointestinal tract. Metabolite patterns observed in plasma, liver and kidney homogenates strongly suggested an important role of the intestinal microflora in the enterohepatic recirculation, but not in nitroreduction of 1-NP prior to absorption from the gastrointestinal tract. This might explain the low levels of radioactivity associated with blood proteins, since 1-nitrosopyrene, a product of nitroreduction of 1-NP, is likely to be involved in protein binding. Levels of radioactivity associated with plasma proteins were approximately four times higher than the levels of radioactivity associated with hemoglobin (401.0 and 84.1 pmol/g protein per micromol 1-NP kg b.w., respectively, at 24 h). Maximal 25% of the associated radioactivity was released following mild alkaline hydrolysis of either hemoglobin or plasma proteins. 1-Aminopyrene was the only released compound after hydrolysis of hemoglobin. In addition to 1-aminopyrene, two more polar unidentified metabolites were detected following hydrolysis of plasma proteins. Association of radioactivity with DNA was highest in the liver at the first moments of observation (7.4 pmol 14C Eq./mg DNA per micromol 1-NP kg b.w.), but decreased rapidly to levels lower than observed for kidney DNA (max. 3.0 pmol 14C Eq./mg DNA per micromol 1-NP kg b.w. at 24 h). In lungs 8-50 times less radioactivity was associated with DNA than observed in the liver and kidneys. The results of this study show, that 1-NP undergoes an extensive and complex biotransformation in vivo, resulting in a variety of metabolites present in blood and tissue homogenates and a diversity of blood protein adducts. Concentrations of plasma metabolites, blood protein adducts and DNA adducts were rather low. In addition, previous studies also showed relatively low concentrations of metabolites present in urine. Therefore, sensitive and selective methods will be needed in order to evaluate the biological fate of 1-NP, associated with diesel exhaust particles, in humans.

Animals↗
PubMed1999

Drugs hazardous to healthcare workers. Evaluation of methods for monitoring occupational exposure to cytostatic drugs.

We review the literature concerning possible health risks for individuals (e.g. healthcare workers and pharmaceutical plant employees) occupationally exposed to cytostatic drugs. Cytostatic drugs possess toxic properties and may therefore cause mutagenic, carcinogenic and teratogenic effects. Hence, individuals handling these drugs in the course of their employment may face health risks. For this reason, it is important to monitor occupational exposure to these drugs. An overview of exposure monitoring methods is presented and their value is discussed. Most studies involve nonselective methods for biological monitoring and biological effect monitoring, such as the urinary mutagenicity assay and analysis of chromosomal aberrations and sister-chromatid exchanges in peripheral blood lymphocytes. The disadvantages of these biological methods are that their sensitivity is low and it cannot be proved beyond any doubt that the results found were caused by occupational exposure to cytostatic drugs. For occupational health services it is important to have sensitive and specific methods for monitoring exposure to cytostatic drugs. One of the most promising methods seems to be the determination of cyclophosphamide in urine using gas chromatography-tandem mass spectrometry. Several studies have demonstrated exposure to cyclophosphamide and other cytostatic drugs, even when protective measures were taken and safety guidelines were followed. To estimate the magnitude of any health effects arising from this exposure, we calculated the risk of cancer due to occupational exposure to cyclophosphamide on the basis of available human and animal dose-response data and the amounts of cyclophosphamide found in urine. The initial results show an extra cancer risk for pharmacy technicians and nurses.

Antineoplastic Agents↗
PubMed1998

Effect of airborne particles from selected indoor and outdoor environments on gap-junctional intercellular communication.

The effect of airborne particles from diesel exhaust, rubber and metal industry, urban air and biological sources (poultry, pig farming, compost industry) on gap-junctional intercellular communication (GJIC) were compared, using HEPA1c1c7 cells. Particles as such were compared with aqueous and organic extracts. Significant inhibition of GJIC by particle suspensions was only observed for the diesel and rubber samples, and for one biological sample (compost). Up to 83% of the inhibition of the whole suspension could be attributed to the particles as such. Washing the particles with organic solvents (aceton, methanol, hexane) did not result in a significant loss of activity from the particles, although the organic fractions showed a significant activity towards GJIC. More active organics was eluted from the rubber industry particles than from the diesel particles by the organic solvent. It is suggested that cancer promoting potential as measured by inhibition of GJIC may vary widely depending on the particle source, and that this effect may be exerted by the particles as such and/or by means of tightly bound bio-active material to the surface.

Agriculture↗
PubMed1998

Mutagenicity and dark toxicity of the second-generation photosensitizer bacteriochlorin a.

Bacteriochlorin a (BCA) is an effective second-generation photosensitizer both in vitro and in vivo. BCA has a high molecular absorption coefficient (32,000 M-1 cm-1) at 760 nm. At this wavelength tissue penetration of light is almost optimal and melanin absorption is relatively low. BCA is preferentially retained in a number of tumour model systems and is rapidly cleared from non-cancerous tissues, thus inducing no or minor skin photosensitivity. Mutagenicity of BCA has been tested using the Salmonella typhimurium strains TA97, TA98, TA100, TA102 and TA104. In all tester strains used, BCA induces, in the dark, a minute increase in the number of revertants. No linear correlation between the number of revertants and the BCA dose is observed. Incubation of isolated rat hepatocytes with BCA, in the dark, does not result in increased cell death as measured by leakage of cytosolic lactate dehydrogenase. A convenient bioassay to test possible genotoxicity in vivo is the established Somatic Mutation and Recombination Test (SMART) on Drosophila melanogaster. Bacteriochlorin was tested for induction of loss of heterozygosity in the white/white+ eye mosaic assay, which predominantly measures homologous mitotic recombination in somatic cells of Drosophila after treatment of larval stages. BCA did not induce loss of heterozygosity above the level of the incorporated controls, with or without illumination. Based on these results, obtained in prokaryotic and eukaryotic cells and in vivo, we are inclined to conclude that the dark toxicity and mutagenic properties of BCA, as measured by the applied bioassays, are negligible.

Animals↗
PubMed1998

Sensitive and selective detection of urinary 1-nitropyrene metabolites following administration of a single intragastric dose of diesel exhaust particles (SRM 2975) to rats.

1-Nitropyrene (1-NP) has been proposed as a marker for exposure to diesel exhaust particles (DEP). Since the extent of the actual intake of 1-NP adsorbed on DEP will be relatively low, sensitive and selective methods are needed regarding human exposure assessment. Two analytical methods are presented for the assessment of 1-NP metabolites in urine of male Sprague-Dawley rats administered a single intragastric dose of native DEP (SRM 2975, 20 mg, 35.7 microgram of 1-NP/g). Enzymatically hydrolyzed urine was extracted using Blue Rayon. The extracts were analyzed directly, using HPLC with postcolumn on-line reduction and fluorescence detection (HPLC-Flu), or were processed further for GC/MS/MS analysis. Although sensitive to several metabolites, the HPLC-Flu method lacked selectivity for quantitation of some important metabolites in rat urinary extracts, and therefore seems suitable for screening purposes only. With regard to GC/MS/MS analysis, derivatization with heptafluorobutyrylimidazole (HFBI) yielded low limits of determination for hydroxy-1-aminopyrenes, hydroxy-N-acetyl-1-aminopyrenes (converted to derivatized hydroxy-1-aminopyrenes by the reagent), and 1-aminopyrene (1.8-9.2 fmol on the column). Derivatization of hydroxy-1-nitropyrenes yielded relatively high limits of determination, and therefore, hydroxy-1-nitropyrenes were reduced to hydroxy-1-aminopyrenes prior to derivatization with HFBI. Intragastric administration of DEP to rats resulted in urinary excretion of 6-hydroxy-N-acetyl-1-aminopyrene, 8-hydroxy-N-acetyl-1-aminopyrene, 6-hydroxy-1-nitropyrene, 8-hydroxy-1-nitropyrene, and 3-hydroxy-1-nitropyrene (7, 1.2, 1.6, 0.3, and 0.5% of the dose within 12 h, respectively). 1-Nitropyrene, N-acetyl-1-aminopyrene, and 3-, 6-, and 8-hydroxy-1-aminopyrene were not observed as urinary metabolites following administration of a single dose of DEP. The observed excretion pattern and urinary metabolite concentrations suggest that 1-NP present on unmodified DEP becomes bioavailable to a large extent and is metabolized in the same way as was previously observed following administration of pure 1-NP. The presented methods are promising for assessment of human exposure to 1-NP, e.g., following exposure to DEP, because of the possibility of analyzing large volumes of urine, the conversion of three types of metabolites to one (the amino metabolites), and the low detection limits that are achieved.

Animals↗
PubMed1997

Determination of hemoglobin adducts following oral administration of 1-nitropyrene to rats using gas chromatography-tandem mass spectrometry.

1-Nitropyrene (1-NP) has successfully been used as a marker for environmental monitoring of exposure to diesel exhaust. This study presents a sensitive and selective method for detection of Hb adducts after oral administration of a single dose 1-NP to rats, by measuring 1-aminopyrene (1-AP) after in vitro hydrolysis of the adducts. Released 1-AP was extracted with hexane and derivatized with heptafluorobutyric acid anhydride prior to GC-MS-MS analysis. Optimal conditions for the release of 1-AP were hydrolysis under nitrogen, in 1 M NaOH at 70 degrees C for 60 min. Analysis of a stock solution of Hb adducts of 1-NP utilizing these conditions showed to be reproducible over a period of several weeks with a coefficient of variance of 9.5%. The determination limit was 10-20 pg 1-AP per 70-90 mg globin. A study of the time course of Hb adduct formation showed a fast absorption and an early peak concentration of released 1-AP, approximately 39 pg 1-AP/mg globin at 3 h after exposure. After the maximum was reached, 1-AP concentrations decreased bi-phasically. Initially a fast decline was observed, followed by a slow decrease to 5.9+/-1.9 pg 1-AP/mg globin at 24 h after administration.

Administration, Oral↗
PubMed1997

Occupational exposure to antineoplastic agents and parameters for renal dysfunction.

To study the nephrotoxic effects of occupational exposure to antineoplastic agents, the early renal effect parameters retinol-binding protein (RBP) and albumin (ALB) were determined in the urine of 11 hospital workers involved in the preparation and administration of antineoplastic agents and in 23 hospital workers not involved in drug handling, who served as nonexposed controls. No significant difference was found between the exposed group and the nonexposed control group with respect to the early renal effect parameters RBP and ALB. Although it was demonstrated that the hospital workers were exposed to cyclophosphamide (CP) and probably other antineoplastic agents, the results of the present study show that these exposure levels did not cause nephrotoxic effects.

Adult↗