The caffeine breath test and caffeine urinary metabolite ratios in the Michigan cohort exposed to polybrominated biphenyls: a preliminary study.

Lambert, George H.; Schoeller, Dale A.; Humphrey, Harold E. B.; Kotake, Alvin N.; Lietz, Helen; Campbell, Monica; Kalow, W.; Spielberg, Stephen P.; Budd, M. D.

doi:10.1289/ehp.9089175

Cited by 44 publications

(19 citation statements)

References 27 publications

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“…For the CYP1A2 substrate [ 13 C]-caffeine, Park et al observed a significant correlation between 1 h single DOB 13 CO 2 / 12 CO 2 ratios and plasma [ 13 C]-caffeine clearance [132]. These results were in agreement with previous studies, in which excellent correlations between caffeine breath test results and caffeine clearance were found [133][134][135][136].…”

Section: Exhaled Breathsupporting

confidence: 82%

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

2015

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Interindividual variability in the expression and function of drug metabolizing cytochrome P (CYP) 450 enzymes, determined by a combination of genetic, non-genetic and environmental parameters, is a major source of variable drug response. Phenotyping by administration of a selective enzyme substrate, followed by the determination of a specific phenotyping metric, is an appropriate approach to assess the in vivo activity of CYP450 enzymes, as it takes into account all influencing factors. A phenotyping protocol should be as simple and convenient as possible. Typically, phenotyping metrics are determined in traditional matrices, such as blood, plasma or urine. Several sampling strategies have been proposed as an alternative for these traditional sampling techniques.In this review, we provide a comprehensive overview of available methods using dried blood spots, hair, oral fluid, exhaled breath and sweat for in vivo CYP450 phenotyping. We discuss the relation between phenotyping metrics measured in these samples and those in conventional matrices, along with the advantages and limitations of the alternative sampling techniques. Reliable phenotyping procedures for several clinically relevant CYP450 enzymes, including CYP1A2, CYP2C19 and CYP2D6, are currently available for oral fluid, breath or dried blood spots, while additional studies are needed for other CYP450 isoforms, such as CYP3A4. The role of hair analysis for this purpose remains to be established. Being non-or minimally invasive, these sampling strategies provide convenient and patient-friendly alternatives for classical phenotyping procedures, which may contribute to the implementation of CYP450 phenotyping in clinical practice. 4 Key Points Phenotyping by administration of a selective probe drug, followed by determination of a specific phenotyping metric, allows to assess the in vivo enzyme activity of CYP450 enzymes, taking into account genetic, non-genetic and environmental influencing factors. In addition to classical sampling techniques, such as blood or urine collection, reliable phenotyping procedures for several clinically relevant CYP450 enzymes are currently available for oral fluid, breath and dried blood spots.

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Section: Exhaled Breathsupporting

confidence: 82%

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

2015

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“…We found only one previous report of the half-life of PBB in humans (13). This study gave a median estimate of 12 years with a range of 4.6-94.7 years.…”

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confidence: 58%

Half-life of polybrominated biphenyl in human sera.

Rosen

Flanders

Friede

et al. 1995

Environ Health Perspect

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(12).The purpose of this study was to estimate the half-life of PBB in human blood sera in order to contribute to our understanding of how continued body burden relates to the possible adverse health consequences of exposure. We found only one previous report of the half-life of PBB in humans (13). This study gave a median estimate of 12 years with a range of 4.6-94.7 years. This estimate was determined by serum measurements from 15 females and 12 males; the half-life for females and males was similar. An experimental half-life determined in rats using a multicompartment model that was then extrapolated to humans was reported as 6.5 years (14); the elimination of PBB from rat serum has been shown to be first order (15). A linear relationship between PBB concentrations in adipose tissue and in serum with a ratio of approximately 300:1 has been demonstrated; the different congeners of PBB do not have significantly different partition ratios (16,17). MethodsWe used data and participants from the Michigan PBB prospective cohort project, which was started in 1975 and was previously described by Pirkle et al. (18). The Michigan investigators enrolled people in the study if they were residents of farms quarantined because of PBB in milk detected at 300 ppb, in eggs detected at 50 ppb (N = 2148), or if they were recipients of food products from quarantined farms (N = 1421). Participation was over 95%. Subjects answered a questionnaire, provided a blood sample, and were followed over time to contribute new blood samples and answer follow-up questionnaires.Participants from the cohort were eligible for inclusion in our analysis if they: 1) lived on a quarantined farm or consumed food products from such a farm; 2) had at least two PBB level determinations between 1976 and 1982 that were a minimum of 1 year apart; 3) were over 18 years of age at the time of their first PBB level measurement; and 4) had an initial PBB level determination of at least 20 pbb. We included the age requirement because continued growth may affect measured PBB levels and half-life (19,20 Ct represents concentration at later times, and k is the rate of decline (21). After taking logarithms and rearranging, this formula is equivalent to -k = Alog(C)/At, where Alog(C) is the change in the log of PBB measurements and At is the change in time between the measurements. The estimated half-life is then equal to log(2)/X. We estimated k for each individual using simple linear regression of eligible PBB measurements and the times between them. We estimated the half-life using two methods in order to better summarize the data. The first method used the median of the individual x values to estimate the halflife. Confidence intervals (CI) were calculated using distribution-free techniques (22). The second method used the mean of the individual X values. Weighting subjects according to the number of available PBB measurements for sensitivity analysis did not change the results. The SAS system was used for calculations

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“…Additional scrum samples were drawn at other times from some members of the cohort for various reasons, including for use in follow-up studies performed from 1982 through 1987 and for additional tests at individuals' requests. Cohort members with higher initial PBB levels were more likely to have multiple measurements because they were oversampled in various follow-up studies (12). In 1997, a total of 2,262 women in the registry had at least one PBB measurement and 1,407 (62%) had two measurements.…”

Section: Study Populationmentioning

confidence: 99%

Determinants of Polybrominated Biphenyl Serum Decay among Women in the Michigan PBB Cohort

Blanck¹,

Marcus²,

Hertzberg³

et al. 2000

Environmental Health Perspectives

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Accidental contamination of the food chain in Michigan in 1973 with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals in 1976. Serum was collected and analyzed for PBB at the time of enrollment and for targeted studies in the following years. We used the archived PBB data to study the elimination of PBB and to identify factors associated with elimination. A total of 380 women ≥ 16 years of age who had an initial PBB level of 2 ppb and at least two serum samples drawn when they were not pregnant were included in the analysis. The mean initial PBB level was 20.9 ppb (median 4) and mean time between the first and last measurement was 4.2 years (range 0.5-11.1). PBB was assumed to reach equilibrium in the body before substantial amounts were eliminated and before the first serum measurements were taken; therefore, the entire body was modeled as a single compartment for PBB with exponential decay. Subject-specific decay rate estimates were regressed on predictor variables including initial age, body mass index (BMI), smoking history, breast-feeding duration, and parity. In women with an initial PBB level < 10 ppb, the median half-life was 12.9 years; in those with > 10 ppb, the median half-life was 28.7 years. Decay was significantly slower among women with an initial BMI at or above the median (BMI ≥ 23). The calculated half-life values are estimates of decay and can be used to estimate body burden of PBB at various points in time other than at the time of serum collection.Address correspondence to M. Marcus, 1518 Clifton Road NE, Room 460, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322 USA. Telephone: (404) . mmarcus@sph.emory.edu. PBBs were used as fire retardants for molded plastic parts, such as the cases of televisions, typewriters, and business machines. In 1973, an industrial accident resulted in the inadvertent substitution of FireMaster for NutriMaster (feed-grade magnesium oxide), a nutritional supplement, into livestock feed. In the following months, many Michigan residents unknowingly ate animal and dairy products that had been contaminated with PBBs. Once the PBB contamination was discovered, public concern prompted assessment of possible adverse health consequences in exposed individuals. A pilot study was conducted in 1974 and a registry of exposed individuals was established in 1976. Details of the incident and the cohort have been described previously (1-5). HHS Public AccessThere is renewed interest in the possible human health effects of PBBs because of their potential role as endocrine disruptors. Endocrine-disrupting chemicals include a family of structurally similar halogenated organics that have the ability to mimic or block normal hormonal activity. They are widespread in occurrence, resistant to degradation, and accumulate in fatty tissue. These chemicals include DDT and its degradation product DDE; 2, 3, 7, 8-tetrachlorodibenzo-P-dioxin (TCDD); polychlorinated biphenyls (PCBs); and PBBs. ...

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The caffeine breath test and caffeine urinary metabolite ratios in the Michigan cohort exposed to polybrominated biphenyls: a preliminary study.

Cited by 44 publications

References 27 publications

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

Alternative Sampling Strategies for Cytochrome P450 Phenotyping

Half-life of polybrominated biphenyl in human sera.

Determinants of Polybrominated Biphenyl Serum Decay among Women in the Michigan PBB Cohort

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