Abstract:
:A few landmarks in the development of dose response in toxicology are presented, with an explanation of why dose should only be considered on a logarithmic scale. Examples are shown, illustrating that the current practice of labeling dose-response curves for carcinogenesis as supralinear, linear or sublinear, is meaningless unless the dose-response scales are defined. Since many reports labeling such curves as supralinear, linear, or sublinear are carried out with dose on a linear scale, the scientific significance of the shape of the curve is obscured. Examples of dose-response curves for carcinogenesis from 2-acetylaminofluorene, N-nitrosodiethylamine, aflatoxins, and radium are shown. In addition, more than 500 National Toxicology Program Technical Reports (NTP-TR) on carcinogenicity were examined; from this database, three groups of studies were selected. The first group consisted of those studies in which the lowest dose produced no tumors and the study had a positive dose response. The second group consisted of those studies with three or more doses, with a positive dose response producing tumors, but in which there were no tumors in the control group. The third group of more than 50 studies was from NTP-TR-00 to NTP-TR-52 that had only two data points with a positive dose response. These studies were all evaluated on the Rozman et al. scale, since it conforms to the laws of nature and allows evaluation of all doses. It was observed that virtually all of these NTP-TR carcinogenicity studies show a linear response when dose is on this logarithmic scale; a clear threshold for carcinogenicity is typical for nearly all of these chemicals. An exponential dose-response curve was a better fit for a few, but experimental error could account for this deviation from linearity. It is pointed out that there is strong experimental evidence that the mere presence of DNA adducts does not necessarily lead to tumor production. Hormesis probably applies to carcinogenesis and proof of this will require abandoning the no threshold concept. Experiments showing that cumulative dose is a better metric than daily dose may require reevaluating almost all carcinogenicity studies.
journal_name
Hum Exp Toxicoljournal_title
Human & experimental toxicologyauthors
Waddell WJdoi
10.1191/0960327106ht633oasubject
Has Abstractpub_date
2006-07-01 00:00:00pages
413-36issue
7eissn
0960-3271issn
1477-0903journal_volume
25pub_type
杂志文章,评审abstract::Occupational chronic solvent encephalopathy (CSE) is associated with a number of neurobehavioural disorders including defects of visual perception. The purpose of this study was to characterize colour vision defects in CSE patients. Colour vision was tested in bright illumination with the Farnsworth-Munsell 100-hue te...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327107076820
更新日期:2007-04-01 00:00:00
abstract::Members of the transforming growth factor (TGF) family have emerged as critical contributors to the choreography of cellular and tissue interactions underlying morphogenesis of the orofacial region. The TGFs beta, and their downstream effector molecules, the Smads, play a pivotal role in normal as well as abnormal dev...
journal_title:Human & experimental toxicology
pub_type: 杂志文章,评审
doi:10.1191/0960327105ht492oa
更新日期:2005-01-01 00:00:00
abstract::Hexafluorocyclobutene (HFCB), a reactive organohalogen gas, causes overwhelming pulmonary oedema. We investigated its effect on the rat lung surfactant system, comparing its action on type II pneumocytes with air-exposed rats. The inflammatory cell population and protein content of bronchoalveolar lavage fluid was ana...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1191/096032701678227686
更新日期:2001-05-01 00:00:00
abstract::The second-generation selective 5-HT2 receptor antagonists and reuptake inhibitors (SARIs) class antidepressants are known to have fewer cardiovascular side effects than the older ones. However, several case reports showed that trazodone, one of the second-generation SARIs, induces QT prolongation, cardiac arrhythmia,...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327115595683
更新日期:2016-05-01 00:00:00
abstract::Severe carbon monoxide (CO) poisoning causes fulminant deaths in common environment as well as neurological sequelae to survivors. Prevention of delayed neurological syndrome (DNS) after exposure to CO, the most important sequela, is based up to date on hyperbaric oxygen administration. Nevertheless, its use remains c...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327120901572
更新日期:2020-06-01 00:00:00
abstract::Sulfur dioxide (SO2) is a common exogenous atmospheric pollutant. Studies have shown that SO2 can cause vasodilation as a gas signaling molecule, but the specific signaling pathways are not well understood. This study aimed to explore the underlying mechanism behind the effects of SO2 on vasodilation of isolated rat a...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327120911428
更新日期:2020-08-01 00:00:00
abstract:AIM:To assess the systemic inflammatory response (SIR) and the multi-organ damage after large-volume liver radiofrequency ablation (RFA) with or without concurrent Pringle maneuver. METHODS:Wistar rats were subjected to 30% liver RFA (group RFA), liver RFA under 30-min Pringle maneuver (group RFA + P), Pringle only (g...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327111401438
更新日期:2011-11-01 00:00:00
abstract::We have investigated the pituitary-testicular axis in a well-characterized population which was occupationally exposed to mercury vapour. Thyroid stimulating hormone and prolactin were also measured as indices of thyroid and pituitary endocrine function. We found no relation between blood or urine mercury levels or le...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719101000309
更新日期:1991-05-01 00:00:00
abstract::Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327115611970
更新日期:2016-09-01 00:00:00
abstract:UNLABELLED:We present the first ever case of homicidal poisoning due to injection of methidathion, an organophosphate insecticide. CASE:A 4-month-old baby presented to the emergency department with chief complaints of unconsciousness and irregular respiration. A bitter odour and an injection site with a greenish blue ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327109348082
更新日期:2009-08-01 00:00:00
abstract::Diabetes mellitus promoted an overproduction of free radicals and an increased incidence of both diabetic nephropathy and liver disease. In this report, we evaluated the effects of Chinese and Brazilian propolis on streptozotocin-induced hepatorenal injury in rats. The results demonstrated that Chinese propolis-treate...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327110387456
更新日期:2011-09-01 00:00:00
abstract:OBJECTIVE:Chlorobenzylidene malononitrile (CS) is the tear gas used by the police. The aim was to evaluate an amphoteric, hypertonic, and chelating rinsing solution in CS exposure. METHODS:The first (CS) group of six police officers was exposed to CS only. The second (preexposure) group of eight sprayed their faces wi...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327115578866
更新日期:2016-02-01 00:00:00
abstract:OBJECTIVE:The present work aimed to investigate the relationship between occupational exposure to airborne molds, serum aflatoxin B1 (AFB1), and liver enzymes of workers handling wheat flour. METHODS:The study included 90 bakers, 100 flour milling workers, and 100 controls with no exposure to flour dust. Workplace asp...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327115573596
更新日期:2016-01-01 00:00:00
abstract::The Na+-taurocholate cotransporting polypeptide (NTCP) acts as the major hepatic basolateral uptake system, and plays a key role in balancing bile flow. The anti-tuberculosis drugs rifampin (RFP) can affect bile flow causing liver injury, while tanshinone IIA (TAN IIA) has the effect of protecting liver. This study ai...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327120979030
更新日期:2020-12-14 00:00:00
abstract::As an input to dose assessments, measurements have been made of the clearance of Pu and Am after subcutaneous implantation in rats for six particulate materials and one dust from the Maralinga test sites. The tissue distribution of Pu and Am were measured in groups of six animals at one month and 6 months after implan...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719301200410
更新日期:1993-07-01 00:00:00
abstract::The fixed-dose procedure (FDP) was introduced as OECD Test Guideline 420 in 1992, as an alternative to the conventional median lethal dose (LD50) test for the assessment of acute oral toxicity (OECD Test Guideline 401). The FDP uses fewer animals and causes less suffering than the conventional test, while providing in...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1191/0960327102ht239oa
更新日期:2002-04-01 00:00:00
abstract::1. Six healthy male volunteers received intravenous injections of 26Al as citrate. Accelerator mass spectrometry and gamma-ray spectrometry were used to determine levels of the tracer in blood and excreta at times up to 5-6 d. 2. There was a rapid clearance from blood (mean 2% of injection remaining after 1 d) and maj...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719501400707
更新日期:1995-07-01 00:00:00
abstract::N-nitrosodimethylamine (NDMA) is a xenobiotic widespread in human environment capable of regulating the lifespan of immune cells. In this study, we examined the roles of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/death receptor 5 (DR5) complex and the Fas molecule in the induction of the extri...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327114551391
更新日期:2015-06-01 00:00:00
abstract::Two studies were performed in order to evaluate cytochrome P450 1A2 mediated caffeine metabolism during different nutritional conditions. 1. In the first study, 23 healthy male non-smokers, mean age 25, changed from a customary mixed diet to a standard diet in 6 days. The 6 day's standard diet was based on bread, pota...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719501401004
更新日期:1995-10-01 00:00:00
abstract::The serial cognitive assessment of ten individuals made between 8 and 26 months after the water at Camelford in Cornwall was accidentally contaminated with aluminium sulphate, showed consistent evidence of impairment of information processing and memory. There was no obvious relationship between these impairments and ...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719301200108
更新日期:1993-01-01 00:00:00
abstract::Omeprazole is one of the most used acid-suppressing medications. This fact emphasizes the questions concerning the safety of this compound. Healthy volunteers (n=33) were included in this prospective study. All study subjects were analysed for their CYP2C19 genotype. Of the 33 individuals, 24 were homozygous for the w...
journal_title:Human & experimental toxicology
pub_type: 临床试验,杂志文章
doi:10.1191/0960327104ht431oa
更新日期:2004-03-01 00:00:00
abstract::1. The methods used to evaluate the toxicological effects of PCBs in animals have been reviewed. 2. The data show that Toxic Equivalency Factors (TEFs) could be developed to assess the potential toxicity of PCB mixtures for certain specific target organ effects (such as the liver and immune system) but would be inappr...
journal_title:Human & experimental toxicology
pub_type: 杂志文章,评审
doi:10.1177/096032719401300901
更新日期:1994-09-01 00:00:00
abstract:PURPOSE:Calcium channel blockers (CCBs) were the most common agents associated with a significant morbidity and mortality rate. The main objective of this study was to examine the publication pattern related to CCBs poisoning at the global level using bibliometric analysis of articles published in SciVerse Scopus onlin...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327115571768
更新日期:2015-11-01 00:00:00
abstract::Teucrium polium L. (Lamiaceae) is a commonly used medicinal plant in folk medicine. Among several uses, T. polium is used to treat male fertility problems. This research was conducted to study the effect of T. polium on spermatogenesis, testosterone level, androgen receptor expression, and fertility in male rats. Admi...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327116688069
更新日期:2017-12-01 00:00:00
abstract::The malignancy of non-small cell lung cancer (NSCLC) largely results from its invasive manner. Secreted frizzled-related proteins (SFRPs) have been recently found to suppress the invasiveness of some cancers. On the other hand, the methylation of SFRPs increases protein degradation to reduce the activity of SFRPs, res...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327117693071
更新日期:2018-02-01 00:00:00
abstract::beta-glucuronidase is considered a sensitive biomarker for acute organophosphorus poisoning. In this well-documented study, multiple plasma samples over time were collected. A decrease in plasma concentration of beta-glucuronidase was surprisingly observed, even within normal range. These findings do not support the h...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327108094614
更新日期:2008-05-01 00:00:00
abstract::1. The herbicide, paraquat, is accumulated by the energy-dependent polyamine uptake pathway of alveolar type II cells. There it undergoes redox cycling that results in an amplified production of toxic reactive oxygen species and depletion of NADPH and other reducing equivalents. These processes account for the lung be...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719401300808
更新日期:1994-08-01 00:00:00
abstract:INTRODUCTION:Anthrax is a bacterial disease caused by the aerobic sporeforming bacterium Bacillus anthracis. It has been suggested that oxidative stress plays an important role in the pathogenesis of B. anthracis. The aim of this study was to investigate serum paraoxonase 1 (PON1) activity, catalase activity, malondial...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327116661020
更新日期:2017-07-01 00:00:00
abstract:OBJECTIVE:Mushroom poisoning is still a significant health-care problem, with the potential to affect blood parameters. The present study analyses the effect of mushroom poisoning on complete blood cell parameters, cell ratios, and cell volume indices and the effect of the mentioned parameters on prognosis/hospital len...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/0960327119855131
更新日期:2019-10-01 00:00:00
abstract::1. Multiple low doses of the direct acting organophosphates, ecothiopate, paraoxon and mipafox produced persistent and additive inhibition of diaphragm acetylcholinesterase. Paraoxon and mipafox had similar effects on brain acetylcholinesterase. There was greater recovery from inhibition between doses for paraoxon and...
journal_title:Human & experimental toxicology
pub_type: 杂志文章
doi:10.1177/096032719701600201
更新日期:1997-02-01 00:00:00