Home About us Contact
|
Home About us Contact | ||
|
|
||
Tolerable Daily Intake (tolerable + daily_intake)
Selected AbstractsPrinciples of risk assessment for determining the safety of chemicals: Recent assessment of residual solvents in drugs and di(2-ethylhexyl) phthalateCONGENITAL ANOMALIES, Issue 2 2004Ryuichi Hasegawa ABSTRACT Risk assessment of chemicals is essential for the estimation of chemical safety, and animal toxicity data are typically used in the evaluation process, which consists of hazard identification, dose,response assessment, exposure assessment, and risk characterization. Hazard identification entails the collection of all available toxicity data and assessment of toxicity endpoints based on findings for repeated dose toxicity, carcinogenicity or genotoxicity and species-specificity. Once a review is compiled, the allowable lifetime exposure level of a chemical is estimated from a dose,response assessment based on several measures. For non-carcinogens and non-genotoxic carcinogens, the no-observed-adverse-effect-level (NOAEL) is divided by uncertainty factors (e.g. with environmental pollutants) or safety factors (e.g. with food additives) to derive a tolerable daily intake (TDI) or acceptable daily intake (ADI), respectively. These factors include interspecies and individual differences, duration of exposure, quality of data, and nature of toxicity such as carcinogenicity or neurotoxicity. For genotoxic carcinogens, low dose extrapolation is accomplished with mathematical modeling (e.g. linearized multistage model) from the point of departure to obtain exposure levels that will be associated with an excess lifetime cancer risk of a certain level. Data for levels of chemicals in food, water and air, are routinely used for exposure assessment. Finally, risk characterization is performed to ensure that the established ,safe' level of exposure exceeds the estimated level of actual exposure. These principles have led to the evaluation of several existing chemicals. To establish a guideline for residual solvents in medicine, the permitted daily exposure (PDE), equivalent to TDI, of N,N-dimethylformamide was derived on the basis of developmental toxicity (malformation) and of N-methylpyrrolidone on the basis of the developmental neurotoxicity. A TDI for di(2-ethylhexyl)phthalate was derived from assessment of testicular toxicity. [source] Seasonal dynamics of the hepatotoxic microcystins in various organs of four freshwater bivalves from the large eutrophic lake Taihu of subtropical China and the risk to human consumptionENVIRONMENTAL TOXICOLOGY, Issue 6 2005Jun Chen Abstract So far, little is known on the distribution of hepatotoxic microcystin (MC) in various organs of bivalves, and there is no study on MC accumulation in bivalves from Chinese waters. Distribution pattern and seasonal dynamics of MC-LR, -YR and -RR in various organs (hepatopancreas, intestine, visceral mass, gill, foot, and rest) of four edible freshwater mussels (Anodonta woodiana, Hyriopsis cumingii, Cristaria plicata, and Lamprotula leai) were studied monthly during Oct. 2003,Sep. 2004 in Lake Taihu with toxic cyanobacterial blooms in the summer. Qualitative and quantitative determinations of MCs in the organs were done by LC,MS and HPLC. The major toxins were present in the hepatopancreas (45.5,55.4%), followed by visceral mass with substantial amount of gonad (27.6,35.5%), whereas gill and foot were the least (1.8,5.1%). The maximum MC contents in the hepatopancreas, intestine, visceral mass, gill, foot, and rest were 38.48, 20.65, 1.70, 0.64, 0.58, and 0.61 ,g/g DW, respectively. There were rather good positive correlation in MC contents between intestines and hepatopancreas of the four bivalves (r = 0.75,0.97, p < 0.05). There appeared to be positive correlations between the maximum MC content in the hepatopancreas and the ,13C (r = 0.919) or ,15N (r = 0.878) of the foot, indicating that the different MC content in the hepatopancreas might be due to different food ingestion. A glutathione (GSH) conjugate of MC-LR was also detected in the foot sample of C. plicata. Among the foot samples analyzed, 54% were above the provisional WHO tolerable daily intake (TDI) level, and the mean daily intakes from the four bivalves were 8,23.5 times the TDI value when the bivalves are eaten as a whole, suggesting the high risk of consuming bivalves in Lake Taihu. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 572,584, 2005. [source] Using Biomonitoring Equivalents to interpret human biomonitoring data in a public health risk contextJOURNAL OF APPLIED TOXICOLOGY, Issue 4 2009Sean M. Hays Abstract Increasingly sensitive analytical tools allow measurement of trace concentrations of chemicals in human biological media in persons from the general population. Such data are being generated by biomonitoring programs conducted by the US Centers for Disease Control and other researchers. However, few screening tools are available for interpretation of such data in a health risk assessment context. This review describes the concept and implementation of Biomonitoring Equivalents (BEs), estimates of the concentration of a chemical or metabolite in a biological medium that is consistent with an existing exposure guidance value such as a tolerable daily intake or reference dose. The BE approach integrates available pharmacokinetic data to convert an existing exposure guidance value into an equivalent concentration in a biological medium. Key concepts regarding the derivation and communication of BE values resulting from an expert workshop held in 2007 are summarized. BE derivations for four case study chemicals (toluene, 2,4-dichlorophenoxyacetic acid, cadmium and acrylamide) are presented, and the interpretation of biomonitoring data for these chemicals is presented using the BE values. These case studies demonstrate that a range of pharmacokinetic data and approaches can be used to derive BE values; fully developed physiologically based pharmacokinetic models, while useful, are not required. The resulting screening level evaluation can be used to classify these compounds into relative categories of low, medium and high priority for risk assessment follow-up. Future challenges related to the derivation and use of BE values as tools in risk management are discussed. Copyright © 2008 John Wiley & Sons, Ltd. [source] Toxicology and risk assessment of coumarin: Focus on human dataMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 2 2010Klaus Abraham Abstract Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible, but was discounted by the European Food Safety Authority in 2004 based on new evidence. This allowed the derivation of a tolerable daily intake (TDI) for the first time, and a value of 0.1,mg/kg body weight was arrived at based on animal hepatotoxicity data. However, clinical data on hepatotoxicity from patients treated with coumarin as medicinal drug is also available. This data revealed a subgroup of the human population being more susceptible for the hepatotoxic effect than the animal species investigated. The cause of the high susceptibility is currently unknown; possible mechanisms are discussed. Using the human data, a TDI of 0.1,mg/kg body weight was derived, confirming that of the European Food Safety Authority. Nutritional exposure may be considerably, and is mainly due to use of cassia cinnamon, which is a popular spice especially, used for cookies and sweet dishes. To estimate exposure to coumarin during the Christmas season in Germany, a telephone survey was performed with more than 1000 randomly selected persons. Heavy consumers of cassia cinnamon may reach a daily coumarin intake corresponding to the TDI. [source] Assessing trace-metal exposure to American dippers in mountain streams of southwestern British Columbia, CanadaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2005Christy A. Morrissey Abstract To develop a suitable biomonitor of metal pollution in watersheds, we examined trends in exposure to nine trace elements in the diet (benthic invertebrates and fish), feathers (n = 104), and feces (n = 14) of an aquatic passerine, the American dipper (Cinclus mexicanus), from the Chilliwack watershed in British Columbia, Canada. We hypothesized that key differences may exist in exposure to metals for resident dippers that occupy the main river year-round and altitudinal migrants that breed on higher elevation tributaries because of differences in prey metal levels between locations or possible differences in diet composition. Metals most commonly detected in dipper feather samples in decreasing order were Zn > Cu > Hg > Se > Pb > Mn > Cd > Al > As. Resident dipper feathers contained significantly higher mean concentrations of mercury (0.64 ,g/g dry wt), cadmium (0.19 ,g/g dry wt), and copper (10.8 ,g/g dry wt) relative to migrants. Mass balance models used to predict daily metal exposure for dippers with different diets and breeding locations within a watershed showed that variation in metal levels primarily was attributed to differences in the proportion offish and invertebrates in the diet of residents and migrants. In comparing predicted metal exposure values to tolerable daily intakes (TDI), we found that most metals were below or within the range of TDI, except selenium, aluminum, and zinc. Other metals, such as cadmium, copper, and arsenic, were only of concern for dippers mainly feeding on insects; mercury was only of concern for dippers consuming high fish diets. The models were useful tools to demonstrate how shifts in diet and breeding location within a single watershed can result in changes in exposure that may be of toxicological significance. [source] | ||||||||||