Importance The optimal temporal approach for reducing nicotine to minimally or nonaddictive levels in all cigarettes sold in the United States has not been determined. Objectives To determine the effects of immediate vs gradual reduction in nicotine content to very low levels and as compared with usual nicotine level cigarettes on biomarkers of toxicant exposure. Design, Setting, and Participants A double-blind, randomized, parallel-design study with 2 weeks of baseline smoking and 20 weeks of intervention was conducted at 10 US sites. A volunteer sample of daily smokers with no intention to quit within 30 days was recruited between July 2014 and September 2016, with the last follow-up completed in March 2017. Interventions (1) Immediate reduction to 0.4 mg of nicotine per gram of tobacco cigarettes; (2) gradual reduction from 15.5 mg to 0.4 mg of nicotine per gram of tobacco cigarettes with 5 monthly dose changes; or (3) maintenance on 15.5 mg of nicotine per gram of tobacco cigarettes. Main Outcomes and Measures Between-group differences in 3 co-primary biomarkers of smoke toxicant exposure: breath carbon monoxide (CO), urine 3-hydroxypropylmercapturic acid (3-HPMA, metabolite of acrolein), and urine phenanthrene tetraol (PheT, indicator of polycyclic aromatic hydrocarbons) calculated as area under the concentration-time curve over the 20 weeks of intervention. Results Among 1250 randomized participants (mean age, 45 years; 549 women [44%]; 958 [77%] completed the trial), significantly lower levels of exposure were observed in the immediate vs gradual reduction group for CO (mean difference, −4.06 parts per million [ppm] [95% CI, −4.89 to −3.23];P < .0055), 3-HPMA (ratio of geometric means, 0.83 [95% CI, 0.77 to 0.88];P < .0055), and PheT (ratio of geometric means, 0.88 [95% CI, 0.83 to 0.93];P < .0055). Significantly lower levels of exposure were observed in the immediate reduction vs control group for CO (mean difference, −3.38 [95% CI, −4.40 to −2.36];P < .0055), 3-HPMA (ratio of geometric means, 0.81 [95% CI, 0.75 to 0.88];P < .0055), and PheT (ratio of geometric means, 0.86 [95% CI, 0.81 to 0.92];P < .0055). No significant differences were observed between the gradual reduction vs control groups for CO (mean difference, 0.68 [95% CI, −0.31 to 1.67];P = .18), 3-HPMA (ratio of geometric means, 0.98 [95% CI, 0.91 to 1.06];P = .64), and PheT (ratio of geometric means, 0.98 [95% CI, 0.92 to 1.04];P = .52). Conclusions and Relevance Among smokers, immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time compared with gradual reduction or a control group, with no significant differences between gradual reduction and control. Trial Registration clinicaltrials.gov Identifier:NCT02139930

The rapid increase in plastic production and consumption has intensified research into human exposure to micro- and nanoplastics (MNPs) and their health effects. This study quantitatively assessed MNP internal exposure levels in non-invasive human samples, focusing on the four most common types of MNPs (≥300 nm): polyethylene terephthalate (PET), polypropylene (PP), low-density polyethylene (LDPE), and polystyrene (PS). Urine samples from 18 volunteers (4 males, 14 females) were analyzed using pyrolysis–gas chromatography–mass spectrometry (Py-GC/MS) with P(E-¹³C₂) as an internal standard. The study developed a straightforward yet effective analytical approach for quantifying MNPs in biological fluids. MNPs were detected in all urine samples, with concentrations ranging from 0.098 to 0.986 μg/mL and an average concentration of 0.268 ± 0.235 μg/mL. LDPE, 0.074 μg/mL (interquartile range: 0.030–0.243 μg/mL), was the most abundant polymer, accounting for 67.72% of the total MNPs, followed by PS at 21.17%, while PP and PET accounted for 7.06% and 4.05%, respectively. The results also suggest that drinking water type may serve as a distinct source of MNPs in urine. This study provides novel evidence on MNP (≥300 nm) internal exposure in humans and the influence of drinking habits, highlighting the application prospects of this method in assessing the potential health risks of MNPs.