Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Nov 2012
Reduced exposure evaluation of an Electrically Heated Cigarette Smoking System. Part 2: Smoke chemistry and in vitro toxicological evaluation using smoking regimens reflecting human puffing behavior.
Chemical analysis of up to 49 harmful and potentially harmful constituents (HPHC) in mainstream smoke, in vitro cytotoxicity of the particulate and gas/vapor phase of mainstream smoke determined in the Neutral Red Uptake assay, and in vitro bacterial mutagenicity of the particulate phase determined in the Salmonella typhimurium Reverse Mutation (Ames) assay are reported for three Electrically Heated Cigarette Smoking System (EHCSS) series-K cigarettes, the University of Kentucky Reference Cigarette 2R4F, and a number of comparator commercial conventional lit-end cigarettes (CC) under ISO machine-smoking conditions and a total of 25 additional smoking regimens reflecting 'human puffing behavior' (HPB). The smoking machines were set to deliver nicotine yields for the EHCSS and comparator CC derived from the 10th percentile to the 90th percentile of nicotine uptake distributions in smokers determined in two clinical studies. Duplication of the smoking intensity 'per cigarette' on a smoking machine may provide an insight into product performance that is directly relevant to obtaining scientific evidence for reduced exposure substantiation based on mainstream cigarette smoke HPHC-to-nicotine regressions. The reported data support an overall evaluation of reduced exposure to HPHC and biological activity.
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Regul. Toxicol. Pharmacol. · Jun 2012
Acetylcholinesterase inhibition dose-response modeling for chlorpyrifos and chlorpyrifos-oxon.
This paper evaluates new data for cholinesterase inhibition with chlorpyrifos (CPF). Marty et al. (2012) recently conducted a CPF cholinesterase inhibition study in rats that included testing of males and females, dosing by gavage or diet, administration in corn oil or milk, and with pups and adults. Additionally, the study included cholinesterase inhibition testing for CPF-oxon, the active moiety that inhibits cholinesterase. ⋯ At the dose levels considered in this analysis, there was no evidence of a difference in responses between males and females, corn oil versus milk administration, or pups versus adults. The data on pups versus adults show that an extra safety factor to protect the young is not needed for CPF. CPF data from the literature suggest that brain cholinesterase inhibition is the most appropriate metric for cholinesterase inhibition risk assessment.
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Regul. Toxicol. Pharmacol. · Dec 2011
Comparative StudyMouth level smoke exposure using analysis of filters from smoked cigarettes: a study of eight countries.
The analysis of spent cigarette filters enables the estimation of the nicotine and tar (nicotine-free dry particulate matter) yields obtained by smokers in their everyday environment and has been shown to correlate well with biomarkers of exposure. Leading products across the range of ISO tar yields were selected from Australia, Brazil, Canada, Germany, Japan, New Zealand, South Africa and Switzerland. At least fifty demographically representative smokers were recruited per product. ⋯ Male smokers obtained higher mean estimated tar and nicotine exposures than female smokers. These gender differences were statistically significant for six countries. Significant correlations were found between estimated nicotine exposure and ISO nicotine yield, and between estimated tar exposure and ISO tar yield (p<0.001).
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Regul. Toxicol. Pharmacol. · Dec 2011
Comparative StudyEstimation and correlation of cigarette smoke exposure in Canadian smokers as determined by filter analysis and biomarkers of exposure.
A clinical study conducted in Canada compared two methods of estimating exposure to cigarette smoke in 192 volunteer subjects: 43 smokers of 4-6 mg, 49 of 8-12 mg and 50 of 14-15 mg ISO tar yield cigarettes and 50 non-smokers. Estimates of mouth level exposure (MLE) to nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene and acrolein were obtained by chemical analysis of spent cigarette filters. Estimates of smoke constituent uptake were achieved by analysis of urinary biomarkers for total nicotine equivalents (nicotine, cotinine, trans-3'-hydroxycotinine plus their glucuronide conjugates), NNK (total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) plus glucuronide), pyrene (1-hydroxy pyrene plus glucuronide) and acrolein (3-hydroxylpropyl-mercapturic acid) plus the nicotine metabolite cotinine in plasma and saliva. ⋯ Unexpectedly high levels of acrolein biomarker found in non-smokers urine on one of the two days sampled emphasised the need for more than one sampling occasion per period and an awareness of non-tobacco sources of smoke constituents under investigation. No consistent dose response, in line with ISO tar yield smoked, of MLE estimates was found for nicotine, pyrene and acrolein and respective biomarkers. The influence of demographics on our results has also been examined.
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Regul. Toxicol. Pharmacol. · Dec 2011
Comparative Study Controlled Clinical TrialA study to evaluate the effect on Mouth Level Exposure and biomarkers of exposure estimates of cigarette smoke exposure following a forced switch to a lower ISO tar yield cigarette.
A forced switch to a lower ISO tar yield cigarette was used in a clinical study, conducted in Germany, that compared two methods of estimating exposure to cigarette smoke. Pre- and post-switch estimates of Mouth Level Exposure (MLE) to nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), pyrene and acrolein were obtained by chemical analysis of spent cigarette filters for nicotine content. Similarly, pre- and post-switch estimates of uptake of these smoke constituents were achieved by analysis of corresponding urinary biomarkers of exposure (BoE): total nicotine equivalents; total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL); total 1-hydroxypyrene (1-OHP), and 3-hydroxypropyl-mercapturic acid (3-HPMA), plus the nicotine metabolite cotinine, in plasma and saliva. ⋯ Changes in daily exposure estimates were determined on a group and individual basis for both methods. The pre- to post-switch directional changes in MLEs and their corresponding BoEs were generally consistent and the MLE/BoE relationship maintained. Switching to a lower yield cigarette generally resulted in reductions in exposure with the resultant exposure level being similar to that seen in regular smokers of the lower yield cigarette.