Switching from usual brand cigarettes to a tobacco-heating cigarette or snus: Part 2. Biomarkers of exposure

Abstract

A randomized, multi-center study of adult cigarette smokers switched to tobacco-heating cigarettes, snus or ultra-low machine yield tobacco-burning cigarettes (50/group) was conducted, and subjects’ experience with the products was followed for 24 weeks. Differences in biomarkers of tobacco exposure between smokers and never smokers at baseline and among groups relative to each other and over time were assessed. Results indicated reduced exposure to many potentially harmful constituents found in cigarette smoke following product switching. Findings support differences in exposure from the use of various tobacco products and are relevant to the understanding of a risk continuum among tobacco products.

Trial registration: ClinicalTrials.gov identifier: NCT02061917.     

Evaluation of urinary 1-hydroxypyrene,S-phenylmercapturic acid,trans,trans-muconic acid, 3-methyladenine, 3-ethyladenine, 8-hydroxy-2′-deoxyguanosine and thioethers as biomarkers of exposure to cigarette smoke

The objective was to evaluate the utility of urinary 1-hydroxypyrene (1-OHP), S-phenylmercapturic acid (S-PMA), trans,trans-muconic acid (t,t-MA), 3-methyladenine (3-MeAd), 3-ethyladenine (3-EtAd), 8-hydroxy-2′-deoxyguanosine (8-OHdG) and thioethers as biomarkers for assessing the exposure in adult smokers who switched from smoking conventional cigarettes to candidate potential reduced exposure products (PREP) or who stopped smoking. Two electrically heated smoking systems (EHCSS) were used as prototype cigarettes that have significant reductions in a number of mainstream smoke constituents as measured by smoking machines relative to those from conventional cigarettes. Urine samples were collected from a randomized, controlled, forced-switching study in which 110 adult smokers of a conventional cigarette brand (CC1) were randomly assigned to five study groups. The groups included the CC1 smoking group, a lower-tar conventional cigarette (CC2) smoking group, EHCSS1 group, EHCSS2 group and a no smoking group that were monitored for 8 days. Biomarkers were measured at baseline and day 8. The daily excretion levels of these biomarkers were compared among the groups before and after switching, and the relationships between the daily excretion levels of these biomarkers and cigarette smoking-related exposure were investigated using Pearson product-moment correlation and multiple regression analyses. It was concluded that under controlled study conditions: (1) 1-OHP, S-PMA and t,t-MA are useful biomarkers that could differentiate exposure between smoking conventional and EHCSS cigarettes or between smoking conventional cigarettes and no smoking; between S-PMA and t,t-MA, the former appeared to be more sensitive; (2) 3-MeAd could only differentiate between smoking conventional cigarettes and no smoking; the results for 3-EtAd were not conclusive because contradictory results were observed; (3) 8-OHdG had a questionable association with smoking and therefore the utility of this biomarker for smoking-related exposure could not be established; and (4) urinary excretion of thioethers as a biomarker lacked sensitivity to demonstrate a clear dose–response relationship in conventional cigarette smokers, although it could differentiate the excretion levels between those subjects who smoked a conventional cigarette and those who stopped smoking.     

Increases in tobacco exposure biomarkers measured in non-smokers exposed to sidestream cigarette smoke under controlled conditions

National surveys of the exposure of non-smokers to secondhand smoke based on serum cotinine analyses have consistently identified certain groups within the population including children, males and non-Hispanic Blacks as having relatively greater exposure. Although these differences in mean serum cotinine concentrations probably represent differences in exposure of individuals in their daily lives, it is also possible that metabolic or other differences in response might influence the results. To better define the nature of those findings, we have examined the response of 40 non-smokers including both men and women and African-Americans and whites to sidestream (SS) cigarette smoke generated by a smoking machine under controlled conditions. In this study, participants were exposed to aged, diluted SS smoke (ADSS) generated in an environmental chamber with a mean air nicotine concentration of 140 μg m^?3 and 8.6?ppm CO for 4?h. Salivary cotinine was measured every 30?min, and serum cotinine samples were taken prior to, and 2?h after exposure. Urinary nicotine metabolites and NNAL, a tobacco-specific nitrosamine, and 4-aminobiphenyl (4-AB) haemoglobin adducts were also measured prior to and 2?h following the exposure. Under these uniform, controlled conditions, we found a similar response to ADSS smoke exposure among all the participants. In all cases a significant increase in biomarker concentration was noted following exposure, and the short-term increases in salivary cotinine concentration were quite similar at approximately 12?pg ml^?1 min^?1 among the groups. In this small study, no significant differences by gender or race were seen in the mean increases observed in cotinine, NNAL or 4-AB adducts following 4?h of exposure. Thus, our results are most consistent with a relatively uniform response in tobacco biomarker concentrations following short-term exposure to ADSS tobacco smoke, and suggest that biomarker measurements are capable of effectively indicating increases in exposure among groups of non-smokers.     

Evaluation of urinary trans-3′-hydroxycotinine as a biomarker of children's environmental tobacco smoke exposure

Abstract

The utility of urinary trans-3′-hydroxy cotinine (3HC) as a biomarker of environmental tobacco smoke (ETS) exposure was investigated in comparison with urinary cotinine (COT), the sum (3HC?+?COT), and ratio of the two nicotine metabolites (3HC/COT). Participants were 150 ETS exposed children (aged 1–44 months) and their parents. Child urine samples were collected during 3weekly baseline assessments and at interviews administered 3, 6, 12, and 18 months after baseline. Findings indicate that 3HC and COT can be measured reliably (rho?=?0.96, 0.88) and show equivalent levels of repeated measures stability (rho?=?0.71, 0.75). COT, 3HC, and 3HC?+?COT showed equally strong associations with air nicotine levels, reported ETS contamination, and reported ETS exposure (r=0.60–0.70). The intraclass correlations of 3HC/COT were lower than those for COT or 3HC. Older children had a higher 3HC/COT ratio than younger children (3.5 versus 2.2), and non-Hispanic White children had a higher ratio than African-American children (3.2 versus 1.9). These findings suggest that COT, 3HC, and 3HC?+?COT are approximately equivalent and equally strong biomarkers of ETS exposure in children. Moreover, 3HC/COT may provide a useful indicator to investigate age- and race-related differences in the metabolism of COT and 3HC.     

Assessment of the total effective xenoestrogen burden in extracts of human placentas

We have standardized a method to assess the total effective xenoestrogen burden (TEXB) in human placentas by the extraction and separation by high-performance liquid chromatography of two fractions containing lipophilic xenoestrogens (alpha) and endogenous hormones (beta), followed by assessing their estrogenicity in MCF-7 breast cancer cell-based E-Screen and Yeast Estrogen Screen (YES) bioassays. The means of TEXB alpha concentrations (in estradiol equivalent (Eeq) units) were 1.32 and 0.77 Eeq pM g^?1 placenta in the E-Screen and YES, respectively; TEXB beta concentrations were 6.97 and 11.56 Eeq pM g^?1 placenta, respectively. The interclass correlation coefficient was low and a fair level of agreement was observed after kappa test correction. According to the E-Screen and YES, TEXB alpha was ≥LOD in 70.0 and 55.0% of the placentas and 92.5 and 82.5% in beta, respectively. Although both bioassays can be recommended for assessing TEXB, there is greater experience with the use of the E-Screen for estrogenic assessment after extensive extraction of complex human matrices.     

Application of two SH-based methods for metallothionein determination in mussels and intercalibration of the spectrophotometric method: laboratory and field studies in the Mediterranean Sea

Metallothionein (MT) induction is widely used as a biomarker of exposure to metals in mussels. The aims of the present work were first to compare the suitability of spectrophotometry and differential pulse polarography (DPP) for MT detection in mussels exposed to 200 ppb cadmium for 9 days in a laboratory experiment and in mussels sampled in different seasons from expected pollution gradients along the Mediterranean Sea; second, to intercalibrate the widely used spectrophotometric method using mussels from Saronikos Gulf. In the intercalibration of the spectrophotometric method, similar results (p>0.05) were obtained by two different research teams indicating a good reproducibility of the technique. However, polarographic and spectrophotometric methods gave significantly (p<0.05) different results in laboratory and field studies. In the laboratory experiment, MT values detected with DPP were nine times higher than with spectrophotometry. The results obtained by the two methods were significantly correlated. Both methods could discriminate between control and exposed mussels. In field studies, MT values obtained by DPP were 34–38-fold higher than with spectrophotometry, and MT concentrations measured by both methods were not correlated. This discrepancy could be due to several factors, including the low levels of bioavailable metals in the studied areas and the possibility that the different methods can measure MT isoforms differentially. Further work is needed to decipher the functions of MT isoforms in mussels. This information is relevant for the application of MT as a biomarker in biomonitoring programmes.     

A need to provide explanations for observed biological effects of radiofrequency exposure

Abstract

Although there is scientific consensus that radiofrequency (RF) exposure at high intensity can cause thermal effects, including well-established adverse health effects, there is still considerable controversy on whether low-intensity RF exposure can cause biological effects, especially adverse health effects. The objective of this paper is to describe several reported “non-thermal” effects that were later shown to be due to a weak thermal effect or an experimental artifact by properly conducted and thorough follow-on scientific research. First, the multiple factors that can cause different RF energy absorption in biological tissues are reviewed and second, several examples of experimental artifacts in published papers are described to demonstrate the importance of paying attention to dosimetry and temperature control. For example, isolated nerve response studies show that when temperature of the RF-exposed tissues is controlled, effects disappeared. During RF exposure, conductive electrodes routinely used in physiological studies have been shown to cause field intensification at the tips or contacts of the electrodes with biological tissue; thus, the RF exposure at the site of measurement could be much higher than the incident field. In some in vitro studies, a lack of temperature uniformity in RF-exposed cell cultures and rate of heating explain changes originally reported to be due to low-level RF exposure. In other studies, detailed dosimetry studies have identified artifacts that explain the reasons why so-called “non-thermal” effects were mistakenly reported. Researchers should look for explanations for their own findings, and not expect others to figure out what was the reason for their observed effects.     

Study of the frequency parameters of EEG influenced by zone-dependent local ELF-MF exposure on the human head

It has been reported that human subjects exposed to electromagnetic fields exhibit changes in human EEG signals at the frequency of stimulation. The aim of the present study was to expose different parts of the brain to extremely low-frequency magnetic fields locally and investigate EEG power spectrum alters at the frequency of stimulation. EEG relative power spectrum were evaluated at 3, 5, 10, 17, and 45 Hz frequencies at T4, T3, F3, Cz, and F4 points, respectively, when these points were exposed to magnetic fields with similar frequencies and 100 μT intensity. The paired t-test results showed that power value of EEG did not alter significantly at the frequency of stimulation (P < 0.05). Further, significant changes in different EEG bands caused by locally exposing to ELF-MF in different points of brain were observed. The changes in the EEG bands were not limited necessarily to the exposure point.     

Minimal Erythema Dose (MED) Testing

Ultraviolet radiation (UV) therapy is sometimes used as a treatment for various common skin conditions, including psoriasis, acne, and eczema. The dosage of UV light is prescribed according to an individual''s skin sensitivity. Thus, to establish the proper dosage of UV light to administer to a patient, the patient is sometimes screened to determine a minimal erythema dose (MED), which is the amount of UV radiation that will produce minimal erythema (sunburn or redness caused by engorgement of capillaries) of an individual''s skin within a few hours following exposure. This article describes how to conduct minimal erythema dose (MED) testing. There is currently no easy way to determine an appropriate UV dose for clinical or research purposes without conducting formal MED testing, requiring observation hours after testing, or informal trial and error testing with the risks of under- or over-dosing. However, some alternative methods are discussed.