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Biomedical subjects

S M Rappaport

Publications and source records attributed to S M Rappaport.

At least 19 recordsLinked to original sources
PubMed2006

Predictors of occupational exposure to styrene and styrene-7,8-oxide in the reinforced plastics industry.

OBJECTIVE: To identify demographic and work related factors that predict blood levels of styrene and styrene-7,8-oxide (SO) in the fibreglass reinforced plastics (FRP) industry. METHODS: Personal breathing-zone air samples and whole blood samples were collected repeatedly from 328 reinforced plastics workers in the Unuted States between 1996 and 1999. Styrene and its major metabolite SO were measured in these samples. Multivariable linear regression analyses were applied to the subject-specific levels to explain the variation in exposure and biomarker levels. RESULTS: Exposure levels of styrene were approximately 500-fold higher than those of SO. Exposure levels of styrene and SO varied greatly among the types of products manufactured, with an 11-fold range of median air levels among categories for styrene and a 23-fold range for SO. Even after stratification by job title, median exposures of styrene and SO among laminators varied 14- and 31-fold across product categories. Furthermore, the relative proportions of exposures to styrene and SO varied among product categories. Multivariable regression analyses explained 70% and 63% of the variation in air levels of styrene and SO, respectively, and 72% and 34% of the variation in blood levels of styrene and SO, respectively. Overall, air levels of styrene and SO appear to have decreased substantially in this industry over the last 10-20 years in the US and were greatest among workers with the least seniority. CONCLUSIONS: As levels of styrene and SO in air and blood varied among product categories in the FRP industry, use of job title as a surrogate for exposure can introduce unpredictable measurement errors and can confound the relation between exposure and health outcomes in epidemiology studies. Also, inverse relations between the intensity of exposure to styrene and SO and years on the job suggest that younger workers with little seniority are typically exposed to higher levels of styrene and SO than their coworkers.

Adolescent↗
PubMed2005

Air samples versus biomarkers for epidemiology.

BACKGROUND: It has been speculated on theoretical grounds that biomarkers are superior surrogates for chemical exposures to air samples in epidemiology studies. METHODS AND RESULTS: Biomarkers were classified according to their position in the exposure-disease continuum-that is, parent compound, reactive intermediate, stable metabolite, macromolecular adduct, or measure of cellular damage. Because airborne exposures and these different biomarkers are time series that vary within and between persons in a population, they are all prone to measurement error effects when used as surrogates for true chemical exposures. It was shown that the attenuation bias in the estimated slope characterising a log exposure-log disease relation should decrease as the within- to between-person variance ratio of a given set of air or biomarker measurements decreases. To gauge the magnitudes of these variance ratios, a database of 12,077 repeated observations was constructed from 127 datasets, including air and biological measurements from either occupational or environmental settings. The within- and between-person variance components (in log scale, after controlling for fixed effects of time) and the corresponding variance ratios for each set of air and biomarker measurements were estimated. It was shown that estimated variance ratios of biomarkers decreased in the order short term (residence time < or =2 days) > intermediate term (2 days < residence time < or =2 months) > long term biomarkers (residence time >2 months). Overall, biomarkers had smaller variance ratios than air measurements, particularly in environmental settings. This suggests that a typical biomarker would provide a less biasing surrogate for exposure than would a typical air measurement. CONCLUSION: Epidemiologists are encouraged to consider the magnitudes of variance ratios, along with other factors related to practicality and cost, in choosing among candidate surrogate measures of exposure.

Air Pollutants↗
PubMed2004

On the importance of exposure variability to the doses of volatile organic compounds.

The connection between occupational exposure to volatile organic compounds (VOCs) and the resulting internal doses is complicated by variability in air levels from day to day and by nonlinear kinetics of metabolism. We investigated long-term liver doses of VOCs and their metabolites using a physiologically based toxicokinetic model, to which 10,000 random 8-h exposures were inputted. Three carcinogenic VOCs were studied (i.e., benzene, perchloroethylene, and acrylonitrile); these compounds are all bioactivated in the liver and represent a wide range of an important toxicokinetic parameter Vmax/QL x KM. For each VOC, simulations were performed using mean air concentrations (muX) between 0.0003 and 1 mg/l (which covers both linear and saturated metabolism) and using coefficients of variation of exposure (CVX) between 0.23 and 2.18 (which includes most occupational settings). Two long-term measures of internal dose were examined, i.e., the area under the liver concentration-time curve (AUCL) and the area under the metabolic rate-time curve (AURC). Interestingly, both AUCL and AURC were linear functions of cumulative exposure (CE, mg x h/l air) even when metabolism was saturated and CVX was large. Yet, at a given CE, both AUCL and AURC were affected by CVX, with the magnitude of the effect increasing with Vmax/QL x KM (i.e., perchloroethylene < benzene < acrylonitrile). Nonetheless, the effects of CVX were typically only a few percent and should be of little consequence unless a VOC has large values of Vmax/QL x KM, muX,and CVX. We conclude that CE should be a sufficient predictor of the dose of either the parent chemical (VOC) or its metabolite in the liver, even when metabolism is nonlinear. We also observed that AUCL and AURC were sensitive to changes in values of model parameters in the high-variability scenarios, suggesting that (when CVX is large) the population variability of AUCL and AURC can be quite large at a fixed CE.

Acrylonitrile↗
PubMed2003

Excessive exposure to silica in the US construction industry.

Exposures to respirable dust and silica were investigated among 36 construction sites in the USA. Personal measurements (n = 151) were analyzed from 80 workers in four trades, namely bricklayers, painters (while abrasive blasting), operating engineers and laborers. Painters had the highest exposures (median values for respirable dust and silica: 13.5 and 1.28 mg/m(3), respectively), followed by laborers (2.46 and 0.350 mg/m(3)), bricklayers (2.13 and 3.20 mg/m(3)) and operating engineers (0.720 and 0.075 mg/m(3)). Mixed models were fitted to the log-transformed air levels to estimate the means and within- and between-worker variance components of the distributions in each trade. We refer to the likelihood that a typical worker from a given trade would be exposed, on average, above the occupational exposure limit (OEL) as the probability of overexposure. Given US OELs of 0.05 mg/m(3) for respirable silica and 3 mg/m(3) for respirable dust, we estimated probabilities of overexposure as between 64.5 and 100% for silica and between 8.2 and 89.2% for dust; in no instance could it be inferred with certainty that this probability was <10%. This indicates that silica exposures are grossly unacceptable in the US construction industry. While engineering and administrative interventions are needed to reduce overall air levels, the heterogeneous exposures among members of each trade suggest that controls should focus, in part, upon the individual sites, activities and equipment involved. The effects of current controls and workplace characteristics upon silica exposures were investigated among operating engineers and laborers. Silica exposures were significantly reduced by wet dust suppression (approximately 3-fold for laborers) and use of ventilated cabs (approximately 6-fold for operating engineers) and were significantly increased indoors (about 4-fold for laborers). It is concluded that urgent action is required to reduce silica exposures in the US construction industry.

Algorithms↗
PubMed2003

Commentary: two seminal contributions of S. A. Roach to the evaluation and control of hazardous substances in air.

S. A. Roach was a pioneer in the assessment and control of hazardous substances in the working environment during the second half of the 20th century. The two papers discussed in this commentary are generally regarded as his most important scientific contributions. The first paper (Roach, 1977) dealt with the determinants of the body burdens of toxic air contaminants. Using simple kinetic models, he showed how levels of toxicants rise and fall in the body according to the patterns of airborne exposures received during relevant time windows. This led to several useful rules of thumb, including the timing of grab samples for 'fast acting' substances, the appropriate duration of air samples relative to the biological half time, how to deal with unusual work schedules, and how to integrate exposure assessment with control. He also offered sage advice regarding the meaning and interpretation of exposure limits, the importance of repeated monitoring, and the extent to which unacceptable levels of exposure might be reduced. In concluding this work, Roach emphasized that the hygienist can fulfill a central role in occupational health simply by intervening to reduce the body burden. The second paper (Roach, 1981) dealt with the design of effective ventilation systems to control worker exposure to toxic airborne contaminants. By developing a series of simple differential equations, Roach evaluated the impact of turbulent diffusion upon industrial ventilation. He emphasized that the stationary contaminant concentration was proportional to the contaminant generation rate and that velocity alone was not a sufficient design criterion to control exposures. Rather, he argued that the equivalent ventilation rate (the ratio of the contaminant generation rate to the steady concentration in the breathing zone) should be the guiding criterion for ventilation design. Throughout both papers, Roach used fundamental principles to tie together exposure assessment and engineering control, and pointed the way to a science for occupational hygiene. The profession can still learn a great deal from these seminal contributions.

Air Pollutants, Occupational↗
PubMed2003

Benzene and naphthalene in air and breath as indicators of exposure to jet fuel.

AIMS: To estimate exposures to benzene and naphthalene among military personnel working with jet fuel (JP-8) and to determine whether naphthalene might serve as a surrogate for JP-8 in studies of health effects. METHODS: Benzene and naphthalene were measured in air and breath of 326 personnel in the US Air Force, who had been assigned a priori into low, moderate, and high exposure categories for JP-8. RESULTS: Median air concentrations for persons in the low, moderate, and high exposure categories were 3.1, 7.4, and 252 microg benzene/m3 air, 4.6, 9.0, and 11.4 microg benzene/m3 breath, 1.9, 10.3, and 485 microg naphthalene/m3 air, and 0.73, 0.93, and 1.83 microg naphthalene/m3 breath, respectively. In the moderate and high exposure categories, 5% and 15% of the benzene air concentrations, respectively, were above the 2002 threshold limit value (TLV) of 1.6 mg/m3. Multiple regression analyses of air and breath levels revealed prominent background sources of benzene exposure, including cigarette smoke. However, naphthalene exposure was not unduly influenced by sources other than JP-8. Among heavily exposed workers, dermal contact with JP-8 contributed to air and breath concentrations along with several physical and environmental factors. CONCLUSIONS: Personnel having regular contact with JP-8 are occasionally exposed to benzene at levels above the current TLV. Among heavily exposed workers, uptake of JP-8 components occurs via both inhalation and dermal contact. Naphthalene in air and breath can serve as useful measures of exposure to JP-8 and uptake of fuel components in the body.

Aerospace Medicine↗
PubMed2001

Determination of styrene and styrene-7,8-oxide in human blood by gas chromatography-mass spectrometry.

Methods of isotope-dilution gas chromatography-mass spectrometry (GC-MS) are described for the determination of styrene and styrene-7,8-oxide (SO) in blood. Styrene and SO were directly measured in pentane extracts of blood from 35 reinforced plastics workers exposed to 4.7-97 ppm styrene. Using positive ion chemical ionization, styrene could be detected at levels greater than 2.5 microg/l blood and SO at levels greater than 0.05 microg/l blood. An alternative method for measurement of SO employed reaction with valine followed by derivatization with pentafluorophenyl isothiocyanate and analysis via negative ion chemical ionization GC-MS-MS (SO detection limit=0.025 microg/l blood). The detection limits for SO by these two methods were 10-20-fold lower than gas chromatographic assays reported earlier, based upon either electron impact MS or flame ionization detection. Excellent agreement between the two SO methods was observed for standard calibration curves while moderate to good agreement was observed among selected reinforced plastics workers (n = 10). Levels of styrene in blood were found to be proportional to the corresponding air exposures to styrene, in line with other published relationships. Although levels of SO in blood, measured by the direct method, were significantly correlated with air levels of either styrene or SO among the reinforced plastics workers, blood concentrations were much lower than previously reported at a given exposure to styrene. The two assays for SO in blood appear to be unbiased and to have sufficient sensitivity and specificity for applications involving workers exposed to styrene and SO during the manufacture of reinforced plastics.

Air↗
PubMed2001

Characterization of metabolic activation of pentachlorophenol to quinones and semiquinones in rodent liver.

Pentachlorophenol (PCP), a widely used biocide, induces liver tumors in mice but not in rats. Metabolic activation of PCP to chlorinated quinones and semiquinones in liver cytosol from Sprague-Dawley rats and B6C3F1 mice was investigated in vitro (1) with microsomes in the presence of either beta-nicotinamide adenine dinucleotide phosphate (NADPH) or cumene hydroperoxide (CHP), (2) with CHP in the absence of microsomes, and (3) with horseradish peroxidase (HRP) and H2O2. Mono-S- and multi-S-substituted adducts of tetrachloro-1,4-benzoquinone (Cl4-1,4-BQ) and Cl4-1,2-BQ and their corresponding semiquinones [i.e. tetrachloro-1,4-benzosemiquinone (Cl4-1,4-SQ) and tetrachloro-1,2-benzosemiquinone (Cl4-1,2-SQ)] were measured by gas chromatography-mass spectrometry (GC-MS). Qualitatively, the metabolites of PCP were the same in both rats and mice for all activation systems. Induction of PCP metabolism by either 3MC or PB-treated microsomes was observed in NADPH- but not in CHP-supported systems. In rats, the amount of induction was comparable with either 3MC or PB. 3MC was a stronger inducer than PB in mice and also induced a greater amount of metabolism than in rats. This suggests that induction of specific P450 isozymes may play a role in the toxicity of PCP to mice. Both HRP/H2O2 and CHP led to production of the full spectrum of chlorinated quinones and semiquinones, confirming the direct oxidation of PCP. CHP (with or without microsomes) converted PCP into much greater quantities of quinones and semiquinones than did microsomal P450/NADPH or HRP/H2O2 in both species. This implies that, under conditions of oxidative stress, endogenous lipid hydroperoxides may increase PCP metabolism sufficiently to enhance the toxicity and carcinogenicity of PCP.

Animals↗
PubMed2001

Urinary benzene as a biomarker of exposure among occupationally exposed and unexposed subjects.

Urinary benzene (UB) was investigated as a biomarker of exposure among benzene-exposed workers and unexposed subjects in Shanghai, China. Measurements were performed via headspace solid phase microextraction of 0.5 ml of urine specimens followed by gas chromatography-mass spectrometry. This assay is simple and more sensitive than other methods (detection limit 0.016 microg benzene/l urine). The median daily benzene exposure was 31 p.p.m. (range 1.65-329 p.p.m.). When subjects were divided into controls (n = 41), those exposed to < or =31 p.p.m. benzene (n = 22) and >31 p.p.m. benzene (n = 20), the median UB levels were 0.069, 4.95 and 46.1 microg/l, respectively (Spearman r = 0.879, P < 0.0001). A linear relationship was observed between the logarithm of UB and the logarithm of benzene exposure in exposed subjects according to the following equation: ln(UB, microg/l) = 0.196 + 0.709 ln (exposure, p.p.m.) (r = 0.717, P < 0.0001). Considering all subjects, linear relationships were also observed between the logarithm of UB and the corresponding logarithms of four urinary metabolites of benzene, namely t,t-muconic acid (r = 0.938, P < 0.0001), phenol (r = 0.826, P < 0.0001), catechol (r = 0.812, P < 0.0001) and hydroquinone (r = 0.898, P: < 0.0001). Ratios of individual metabolite levels to total metabolites versus UB provide evidence of competitive inhibition of CYP450 enzymes leading to increased production of phenol and catechol at the expense of hydroquinone and muconic acid. Among control subjects UB was readily detected with a mean level of 0.145 microg/l (range 0.027-2.06 microg/l), compared with 5.63 microg/l (range 0.837-26.38 microg/l) in workers exposed to benzene below 10 p.p.m. (P < 0.0001). This suggests that UB is a good biomarker for exposure to low levels of benzene.

Benzene↗
PubMed2001

Physiological modeling of the relative contributions of styrene-7,8-oxide derived from direct inhalation and from styrene metabolism to the systemic dose in humans.

Workers in the reinforced plastics industry are exposed to large quantities of styrene and to small amounts of the carcinogen, styrene-7,8-oxide (SO), in air. Since SO is also the primary metabolite of styrene, we modified a published physiologically based pharmacokinetic (PBPK) model to investigate the relative contributions of inhaled SO and metabolically derived SO to the systemic levels of SO in humans. The model was tested against air and blood measurements of styrene and SO from 252 reinforced plastics workers. Results suggest that the highly efficient first-pass hydrolysis of SO via epoxide hydrolase in the liver greatly reduces the systemic availability of SO formed in situ from styrene. In contrast, airborne SO, absorbed via inhalation, is distributed to the systemic circulation, thereby avoiding such privileged-access metabolism. The best fit to the model was obtained when the relative systemic availability (the ratio of metabolic SO to absorbed SO per unit exposure) equaled 2.75 x 10(-4), indicating that absorbed SO contributed 3640 times more SO to the blood than an equivalent amount of inhaled styrene. Since the ratio of airborne styrene to SO rarely exceeds 1500 in the reinforced plastics industry, this indicates that inhalation of SO presents a greater hazard of cytogenetic damage than inhalation of styrene. We conclude that future studies should assess exposures to airborne SO as well as styrene.

Air Pollutants, Occupational↗
PubMed2001

A mixture model for occupational exposure mean testing with a limit of detection.

Information from detectable exposure measurements randomly sampled from a left-truncated log-normal distribution may be used to evaluate the distribution of nondetectable values that fall below an analytic limit of detection. If the proportion of nondetects is larger than expected under log normality, alternative models to account for these unobserved data should be considered. We discuss one such model that incorporates a mixture of true zero exposures and a log-normal distribution with possible left censoring, previously considered in a different context by Moulton and Halsey (1995, Biometrics 51, 1570-1578). A particular relationship is demonstrated between maximum likelihood parameter estimates based on this mixture model and those assuming either left-truncated or left-censored data. These results emphasize the need for caution when choosing a model to fit data involving nondetectable values. A one-sided likelihood ratio test for comparing mean exposure under the mixture model to an occupational exposure limit is then developed and evaluated via simulations. An example demonstrates the potential impact of specifying an incorrect model for the nondetectable values.

Algorithms↗
PubMed2001

Comparison of self-assessment and expert assessment of occupational exposure to chemicals.

OBJECTIVES: Occupational assessments of chemical exposure are often inadequate because of difficulties in obtaining sufficient numbers of measurements by trained professionals (experts). The objective of this study was to determine whether workers can provide unbiased data via self-assessments of exposure facilitated by the use of simple passive monitors for personal sampling. METHODS: Untrained workers obtained personal measurements of their exposures to gaseous contaminants (terpenes in sawmills and styrene in reinforced plastics factories) with passive monitors and written instructions. To study the validity of the self-assessments, an occupational hygienist performed exposure measurements on the same occupational groups after the workers had obtained two or more measurements independently. The potential bias of the self-assessments was evaluated by comparing the self-assessments with the expert assessments in mixed-effects statistical models. RESULTS: A total of 153 terpene (97 self and 56 expert) and 216 styrene (159 self and 57 expert) measurements were obtained from four sawmills and six reinforced plastics factories, respectively. No significant differences in the geometric mean exposures were observed between the self-assessments and the expert assessments in 3 of 4 sawmills and 5 of 6 reinforced plastics factories (P > 0.10). The potential bias of the self-assessments of exposure ranged from less than 0.1% to 102% and was less than 17% in 9 of the 10 groups investigated. CONCLUSIONS: The results indicate that untrained, unsupervised workers are able to collect consistently unbiased exposure data by employing currently available passive monitors.

Air Pollution, Indoor↗
PubMed2001

Protein adducts of 1,4-benzoquinone and benzene oxide among smokers and nonsmokers exposed to benzene in China.

Hemoglobin (Hb) and albumin (Alb) adducts of the benzene metabolites benzene oxide (BO) and 1,4-benzoquinone (1,4-BQ) were analyzed by gas chromatography-mass spectrometry in 43 exposed workers and 44 unexposed controls from Shanghai, China, as part of a larger cross-sectional study of benzene biomarkers. When subjects were divided into controls (n = 44) and workers exposed to </=31 ppm (n = 21) and >31 ppm (n = 22) of benzene, median 1,4-BQ-Alb adducts were 2110, 5850, and 13,800 pmol/g Alb, respectively (correlation with exposure: Spearman r = 0.762; P < 0.0001); median BO-Alb adducts were 106, 417, and 2400 pmol/g Alb, respectively (Spearman r = 0.877; P < 0.0001); and median BO-Hb adducts were 37.1, 50.5, and 136 pmol/g Hb, respectively (Spearman r = 0.757; P < 0.0001). To our knowledge, this is the first observation that adducts of 1,4-BQ are significantly correlated with benzene exposure. When compared on an individual basis, Alb adducts of 1,4-BQ and BO and Hb adducts of BO were highly correlated with each other and with urinary phenol and hydroquinone (P < 0.0001 for all of the comparisons). Although detectable in the assays, Hb adducts of 1,4-BQ and both Hb and Alb adducts of 1,2-BQ produced erratic results and are not reported. Interestingly, cigarette smoking increased Alb adducts of 1,4-BQ but not of BO, suggesting that benzene from cigarette smoke was not the primary contributor to the 1,4-BQ adducts.

Benzene↗
PubMed2001

Simultaneous assessment of occupational exposures from multiple worker groups.

The methods developed by Rappaport et al. [Ann. Occup. Hyg. 39 (1995) 469] and Lyles et al. [J. Agri. Bio. Environ. Stat. 2 (1997a) 64; Ann. Occup. Hyg. 41 (1997b) 63]) for assessing workplace exposures on a group-by-group basis are extended to allow for the simultaneous assessment of data from multiple worker groups within the same industry. These extended methods allow models to be fit simultaneously to data on all groups in a study, even when some of the groups might not contribute adequate information to be modeled separately. We assume that the exposures are log-normally distributed, and that they can be adequately modeled by a mixed effects regression model with parameters for exposure levels and for between- and within-worker variance components. Simultaneously analyzing data from multiple groups is only advantageous when at least one of these variance components can be assumed to be homogeneous across the groups. Here, we advocate testing an assumption of homogeneous within-worker variance components, sigma(2)(w,h), using a likelihood ratio test to choose between a full model (distinct sigma(2)(w,h) for each group) and a reduced model (common sigma(2)(w) across groups). We then develop a procedure, which is conditional on the results of the likelihood ratio test, for testing whether or not each group of workers is overexposed to the contaminant of interest. This modeling and testing procedure was applied to 39 different data sets, each containing data for multiple groups, from a wide variety of industries. For these data, the testing procedure generally resulted in the same conclusion regarding overexposure under both models, even in those data sets where the within-worker variance components appeared to be quite heterogeneous. We also conducted a small simulation study to estimate the significance level of the proposed testing procedure, and found that the significance levels tended to be adequately close to the specified nominal level when a likelihood ratio test with significance level of at least 0.01 was used as a preliminary test. Additionally, we make specific recommendations for designing studies and suggest a method for determining whether engineering and administrative controls or individual-level interventions would be of most benefit to an overexposed group of workers.

Humans↗
PubMed2000

Measurement of styrene-7,8-oxide and other oxidation products of styrene in air.

Styrene-7,8-oxide (SO) is generated at low concentrations from the oxidation of styrene during the processing of reinforced plastics. Since exposure to SO has important health implications, we developed air sampling and analytical methods to measure low levels of airborne SO in the presence of styrene and its other oxidation products, namely phenylacetaldehyde (PAA) and acetophenone (AP). Both active and passive air monitors were used. The active sampling method, which employed adsorption on Tenax, was suitable for measuring SO, PAA and AP but had limited capacity for styrene due to breakthrough. The passive monitor employed a carbon adsorbent and was suitable for measurement of styrene and SO but not PAA and AP due to poor recovery. After sampling, the analytes were extracted from the adsorbents with ethyl acetate and measured by gas chromatography with flame ionization detection or mass spectrometry. By maintaining the injection port at 70 degrees C, the thermal rearrangement of SO to PAA was minimized. Recovery of styrene and SO from the passive monitor depended upon loading and was corrected by linearization of the Freundlich isotherm. The limits of detection for SO, PAA, and AP were 0.2 ppb using the active monitor, and for SO was 1 ppb using the passive monitor. The sampling precision for SO (RSD from personal measurements) was 5.0% for the passive monitor and was 13.4% for the active monitor over a range of exposures from 5-150 ppb. The corresponding precision for styrene was 5.3% for the passive monitor for levels ranging from 1.2 to 104 ppm. Measurements of 235 personal exposures with the active monitor in 12 facilities manufacturing fiberglass-reinforced plastics (FRP) showed that levels of AP and PAA were below 7.8 ppb and 5 ppb, respectively. In contrast, SO averaged 30.4 ppb (SE=2.4) in these FRP facilities, ranging from below 0.2 ppb to 190 ppb. The active monitor was also used to detect airborne SO at levels of approximately equals 1 ppb in one facility manufacturing styrene butadiene rubber, suggesting that SO is generally present during the polymerization of styrene. Personal passive monitoring in the 12 FRP facilities (n = 657) revealed mean concentrations of styrene ranging between 1.8 and 55.4 ppm, and for SO between 1.7 and 62.6 ppb. The ratio of the mean styrene level to the mean SO level varied between 449:1 and 1,635:1 among the 12 FRP facilities.

Air Pollutants↗
PubMed2000

Stability of hemoglobin and albumin adducts of benzene oxide and 1,4-benzoquinone after administration of benzene to F344 rats.

The stability of cysteinyl adducts of benzene oxide (BO) and mono-S-substituted cysteinyl adducts of 1,4-benzoquinone (1,4-BQ) was investigated in both hemoglobin (Hb) and albumin (Alb) following administration of a single oral dose of 400 mg [U-14C/13C6]benzene/kg body weight to F344 rats. Total radiobound adducts to Hb were stable, as were adducts formed by the reaction of [13C6]BO with cysteinyl residues on Hb. In both cases adduct stability was indicated by zero-order kinetics with decay rates consistent with the lifetime of rat erythrocytes. Hb adducts of 1,4-BQ were not detected, possibly due to the production of multi-S-substituted adducts within the erythrocyte. Regarding Alb binding, total radiobound adducts decayed more rapidly than expected (half-life of 0.4 days), suggesting that uncharacterized benzene metabolites were noncovalently bound or formed unstable adducts with Alb. Although adducts from reactions of BO and 1,4-BQ with Alb both decayed with rates consistent with those of Alb turnover in the rat, the half-life for 1,4-BQ-Alb (2.5 days) was shorter than that for BO-Alb (3.1 days), suggesting some instability of 1,4-BQ-Alb. Assuming similar rates of adduct instability in humans and rats, the 1,4-BQ-Alb adducts would be eliminated with a half-life of approximately 8 days, compared with BO-Alb, which would be expected to turnover with Alb (half-life of approximately 21 days).

Albumins↗