The Caffeine Breath Test and Caffeine Urinary Metabolite Ratios in the Michigan Cohort Exposed to Polybrominated Biphenyls: A Preliminary Study

Abstract

A field biochemical epidemiology study was conducted using the Michigan cohort consisting of 51 rural residents exposed to polybrominated biphenyls (PBB). The study had three major objectives: a) to determine the serum half-life of the major PBB congener, hexabromobiphenyl (HBB), in the human, b) to determine if the PBB-exposed subjects had elevated cytochrome P4501 function as determined by the caffeine breath test (CBT) and the caffeine urinary metabolite ratio (CMR), and c) to determine the applicability of the CBT and CMR in field studies. PBB serum levels were detected in 36 of the 51 PBB-exposed subjects. The serum half-life of HBB was determined by comparing the current serum HBB values to the subject's previous serum values obtained 5 to 8 years earlier. The median HBB half-life was 12 years (range 4-97 years). The CBT and CMR were elevated in the subjects exposed to PBBs as compared to the values obtained from urban nonsmokers and were similar to those found in adults who smoke. A gender effect was seen in the PBB-exposed subjects, the median CBT and CMR values of the females being lower than the values of males. There was a correlation between the CBT and the HBB serum values (r2=0.2, p=0.01) but not between CMR and HBB serum values. The CBT and CMR were easily conducted in the field and appear to be useful metabolic probes of cytochrome P-4501 activity in human environmental toxicology.

Cytochrome P450 1A2 activity and incidence of thyroid disease and cancer after chronic or acute exposure to dioxins

“…The UMR did not reflect CYP1A2 induction adequately in that study. A similar superiority of the caffeine breath test over the UMR was demonstrated by others that investigated 51 rural residents exposed to polybrominated biphenyls via a contamination of the food chain in Michigan and compared to urban controls . A correlation between the caffeine breath test and the PBB serum values was demonstrated ( r 2 = .2, P = .01) but not with the caffeine UMR.…”

“…A similar superiority of the caffeine breath test over the UMR was demonstrated by others that investigated 51 rural residents exposed to polybrominated biphenyls via a contamination of the food chain in Michigan and compared to urban controls. 32 A correlation between the caffeine breath test and the PBB serum values was demonstrated (r 2 = .2, P = .01) but not with the caffeine UMR. Others reported the absence of a correlation between CYP1A2 activity measured with caffeine UMR and PCB exposure in 305 Faroese residents.…”

Relationship between polychlorinated biphenyl 126 treatment and cytochrome p4501a activity in chickens, as measured by in vivo caffeine and ex vivo ethoxyresorufin metabolism

“…The CBT caffeine substrate dose that was chosen for use in this study, 3 mg/kg body weight, is the same as has been used in human studies [17, 19, 20, 36]. Of the three caffeine substrate doses tested in this study, 3 mg/kg body weight provided the greatest discrimination between PCB‐treated chickens and controls.…”

“…A further discrimination against 13 C occurs in the transformation of carbohydrate to protein and lipid such that lipids have the lowest 13 C abundance within a given food chain. In human breath tests, subjects are often asked to fast for 8 h prior to the CBT in order to minimize baseline shifts [20]. After such a fast, the subject is usually metabolizing well‐mixed endogenous fuel sources in constant proportion [38].…”

“…This compound is convenient for CBT use because it is commercially available, unlike the trilabelled material. Caffeine labelled in the 3‐methyl position is commonly used in human CBTs [19, 20] since CYP1A‐mediated CNDM has been found to occur only at that position in humans [21]. However, there are species differences in methyl position specificity of CYP1A‐mediated CNDM [22, 23].…”