Showing papers in "Regulatory Toxicology and Pharmacology in 2008"

TL;DR: Findings in human populations are consistent with animal data suggesting that PAEs and their metabolites produce toxic effects in the reproductive system, but it is not yet possible to conclude whether phthalate exposure is harmful for human reproduction.

TL;DR: A probabilistic analysis of available sensitisation data, similar to that used in the development of the TTC, is presented and it is concluded that a Dermal Sensitisation Threshold (DST) can be established below which there is no appreciable risk of sensitisation, even for an untested ingredient.

TL;DR: The principles of the recommended approach, detailed review of all the information used in the dermal sensitization QRA approach for fragrance ingredients and key conclusions for its use now and refinement in the future are presented.

TL;DR: Although much higher levels of each of these amino acids have been tested without adverse effects and may be safe, the data for intakes above these levels are not sufficient for a confident conclusion of long-term safety, and therefore these values are not selected as the OSLs.

TL;DR: Environmental risk-based ranking procedures of veterinary substances would benefit from more detailed use data, as available data sources and quality, the method and possible refinement of the approach are discussed.

TL;DR: This paper provides guidance on methods for conveying information to the general public, the health care community, regulators and other interested parties regarding how chemical-specific BEs are derived, what they mean in terms of health, and the challenges and questions related to interpretation and communication of biomonitoring data.

TL;DR: It is shown that oral steviol glycosides, taken as sweetener are well tolerated and have no pharmacological effect, except for the placebo Type 1 diabetics group where a significant difference was observed for systolic BP and glucose.

TL;DR: Clinical and epidemiological findings concerning the neurodevelopmental toxicity of MeHG are reviewed and much attention is focussed on the potential impact of factors, such as diet and nutrition, gender, pattern of exposure and co-exposure to other neurotoxic pollutants, which may modulate MeHg toxic effects.

TL;DR: It was concluded that the no-observed-effect level for subjective and objective eye irritation due to formaldehyde exposure was 0.5 ppm, indicating eye irritation as the most sensitive parameter.

TL;DR: The process of PBPK model development is described and issues related to the specification of model structure and parameters, model evaluation, and consideration of uncertainty are highlighted.

TL;DR: It is concluded that scientific data are lacking so far to consider higher alcohols as a likely cause for the adverse effects of surrogate alcohol, and a reasonable preliminary guideline level is 1000 g/hl of pure alcohol for the sum of all higheralcohols.

TL;DR: This article provides an updated overview of the main neuromorphological and neurobehavioral changes reported in non-human primates and rodents following developmental exposure to MeHg, with particular reference to the delayed onset of symptoms and the persistency of central nervous system injury/dysfunction.

TL;DR: The current process of the safety evaluation of GM versus conventionally bred plants is not well balanced and it is proposed to develop a general screening frame for all newly developed plant varieties to select varieties that cannot, on the basis of scientific criteria, be considered as safe as plant varieties that are already on the market.

TL;DR: Next steps in the development of guidance for GMP and research to improve the scientific basis of the models are described based on a review of the current status of the application of physiologically based pharmacokinetic (PBPK) models in risk assessments in Europe, Canada, and the United States.

TL;DR: Low-level arsenic exposure alone did not appear to be a significant independent risk factor for bladder cancer and more studies with detailed smoking history will help resolve whether smoking is an effect modifier.

TL;DR: Time-trend analysis shows that the exposure to dioxin-like compounds in most of the foods has further decreased by 35% over the past five years, mainly influenced by lower levels in meat and milk.

TL;DR: The weight of evidence fully supports a conclusion that non-asbestiform amphiboles do not increase the risk of lung cancer or mesothelioma.

TL;DR: The conclusion of the working group is that acute toxicity studies are not needed prior to first clinical trials in humans and information can be obtained from other studies, which are performed at more relevant doses for humans and are already an integral part of drug development.

TL;DR: No significant toxicological risks are found from typical usage of these topical insect repellents, DEET and picaridin, and the Margin of Exposure (MOE) method (NOEL divided by the estimated exposure), whereby estimated MOEs were compared to an MOE of 100.

TL;DR: This document reviews available pharmacokinetic data and models for cadmium and applies them to existing health-based exposure guidance values from the US Environmental Protection Agency, the Agency for Toxic Substances and Disease Registry, Health Canada, and the World Health Organization, to estimate corresponding BE values for Cadmium in blood and urine.

TL;DR: There is strong evidence of a much lower hazard associated with the shorter, thicker fibers of the non-asbestos amphiboles, than is found for the asbestos analogues of the same mineral.

TL;DR: The overall risk potential of khat use in the Netherlands is estimated as very low, and a similar conclusion may be drawn for countries with a comparable prevalence of k hat use and khat related public order disturbance.

TL;DR: Health-based OELs are set for direct-acting genotoxic compounds where the life-time risks may be estimated from the low-dose linear non-threshold extrapolation, allowing a politically based exposure level to be set.

TL;DR: A physiologically based pharmacokinetic model for melamine was developed for rats and extrapolated to pigs, providing evidence of the usefulness in species extrapolation over a range of dosing scenarios and can be used to protect the food supply after accidental exposure in the face of little in the target species.

TL;DR: Clinical data, particularly dose-response data derived from sensitized patients, should be included in risk assessment, as it reflects degree of exposure as well as intrinsic potency in the general population.

TL;DR: In most cases the toxicology studies were predictive of common clinical adverse reactions, but were poorly predictive of rare clinical events or some serious adverse reactions.

TL;DR: The evidence which supports dose per unit area as being the critical exposure metric in the induction of skin sensitization is reviewed, and the mechanistic bases for this relationship are reviewed.

TL;DR: Under the conditions of these in vitro and in vivo studies, the EHCSS demonstrated significantly lower biological activity compared to conventional cigarettes, and may suggest the potential for reductions in human smokers.

TL;DR: This study is designed to confirm the No-Observed-Effect-Level for induction of dermal sensitization in a normal human population.

TL;DR: To date there is no indication of an increased risk of mesothelioma resulting from non-commercial fiber exposure in the taconite industry, and a practical threshold seems to exist for exposure to chrysotile, it is unlikely to exists for the amphibole asbestos minerals, especially for crocidolite.