Regulatory toxicology and pharmacology : RTP
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Regul. Toxicol. Pharmacol. · Oct 2009
Comparative StudyA study to estimate and correlate cigarette smoke exposure in smokers in Germany as determined by filter analysis and biomarkers of exposure.
A clinical study, conducted in Germany, compared two methods of estimating exposure to cigarette smoke. 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. Estimates of smoke constituent uptake were achieved by analysis of corresponding urinary biomarkers: for nicotine; total nicotine equivalents (nicotine, cotinine, trans-3'-hydroxycotinine plus their glucuronide conjugates), for NNK; (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) plus glucuronide, for pyrene; 1-hydroxy pyrene (1-OHP) plus glucuronide and for acrolein; 3-hydroxylpropyl-mercapturic acid (3-HPMA) plus the nicotine metabolite cotinine in plasma and saliva. ⋯ Mean MLE estimates for nicotine, NNK and pyrene showed a dose response in line with ISO tar yield smoked, with 10 mg > 4 mg >1 mg, and for acrolein 10 mg> 4 mg > *1mg (where * indicates not significant at 95% confidence level). The mean exposure estimates from biomarkers for nicotine, NNK and acrolein also showed a dose response in line with ISO tar yield with 10 mg > 4 mg > 1 mg > NS, and for pyrene 10 mg > *4 mg> 1 mg> NS. This study shows that estimates of exposure obtained by filter analysis and biomarkers of exposure correlate significantly over a wide range of smoke exposures and that filter analysis may provide a simple and effective alternative to biomarkers for estimating smokers' exposure.
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Regul. Toxicol. Pharmacol. · Aug 2009
Further evaluation of the utility of "sliding window" FASTA in predicting cross-reactivity with allergenic proteins.
FAO/WHO has recommended that IgE cross-reactivity between a transgenic protein and allergen be considered when there is greater than 35% identity over a sliding "window" of 80 amino acids. In a previous work, we evaluated the false positive and negative rates observed using the FAO/WHO criteria versus conventional, whole protein FASTA analyses [Ladics, G. S., Bannon, G. ⋯ Examination of the matches not recognized by the conventional search revealed two scenarios: (1) "true" false positives consisting of low statistical significance (as measured by E score, i.e., a measure of the potential random occurrence of aligned sequences used to evaluate the significance of an observed alignment) alignments not contained in the conventional FASTA outputs, and (2) above-threshold sliding window alignments that fell below the 35% identity threshold with the conventional FASTA analysis. Although some alignments within this second group were between regions of low sequence complexity, where there was little/no change in E score, the majority of the alignments displayed more significance (lower E scores) under the conventional FASTA algorithm, yet did not meet the threshold defined by FAO/WHO. These data question the utility of the FAO/WHO recommended sliding window FASTA compared to the traditional whole sequence FASTA analysis coupled with appropriate statistical analysis.
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Regul. Toxicol. Pharmacol. · Feb 2009
ReviewEvaluation of potential human carcinogenicity of the synthetic monomer ethyl acrylate.
Ethyl acrylate (EA) is an acrylic monomer used in the manufacture of a variety of polymers and copolymers as components of many commercially important products. Human exposure to EA occurs primarily in the workplace via inhalation or dermal contact. In F344 rat and B6C3F(1) mouse studies of EA carcinogenicity conducted by the National Toxicology Program [National Toxicology Program, NTP, 1986. ⋯ This again supports a non-genotoxic MOA. In addition, the route and rate of EA exposure in rodents for forestomach neoplasia are irrelevant to potential human exposure, since humans do not have forestomach and are not exposed to EA by oral bolus. Thus, the weight of evidence indicates that the tumors produced in the rodent carcinogenicity studies arise from conditions that are irrelevant for human risk assessment.
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Regul. Toxicol. Pharmacol. · Feb 2009
FDA'S food ingredient approval process: Safety assurance based on scientific assessment.
Fifty years ago, the Food and Drug Administration (FDA) began implementing new provisions of the Federal Food, Drug, and Cosmetic Act aimed at assuring the safety of new food additives before they enter the marketplace. Today, the agency's procedures for premarket evaluation of food additive safety have evolved into a scientifically rigorous, sound and dependable system whose objective and independent evaluations by FDA scientists assure that new food additives are safe for their intended uses before they arrive on the consumer's plate. Although controversy often surrounds food additives in the popular media and culture, and science-based challenges to FDA's decisions do arise, the agency's original safety judgments successfully withstand these challenges time and again. This article reviews the basic components of the FDA's decision-making process for evaluating the safety of new food additives, and identifies characteristics of this process that are central to assuring that FDA's decisions are marked by scientific rigor and high integrity, and can continue to be relied on by consumers.