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Mutations induced in somatic cells and germ cells are responsible for a variety of human diseases, and mutation per se has been considered an adverse health concern since the early part of the 20th Century. Although in vitro and in vivo somatic cell mutation data are most commonly used by regulatory agencies for hazard identification, that is, determining whether or not a substance is a potential mutagen and carcinogen, quantitative mutagenicity dose-response data are being used increasingly for risk assessments. Efforts are currently underway to both improve the measurement of mutations and to refine the computational methods used for evaluating mutation data. We recommend continuing the development of these approaches with the objective of establishing consensus regarding the value of including the quantitative analysis of mutation per se as a required endpoint for comprehensive assessments of toxicological risk. Environ. Mol. Mutagen. 61:34-41, 2020. © 2019 Wiley Periodicals, Inc.

E-cigarettes are increasingly common around the world, particularly among youth. Ingestion of nicotine-containing e-liquid, while relatively rare, is the major toxicological risk associated with their use. Current Australian regulation has nicotine for use in e-cigarettes listed as a dangerous poison in Schedule 7, with its supply or sale illegal in all states and territories, while regulation on the sale of e-cigarettes and accessories varies by state. However, with increasing evidence that e-cigarettes produce far fewer toxic by-products than their combustible counterparts perhaps it is time to review this regulation.

Background Hair dyeing is very common and may cause allergic contact dermatitis. Oxidative (often termed permanent or semi-permanent) hair dye products have constituted the focus of market surveys and toxicological risk assessments, while non-oxidative (semi-permanent, temporary or direct) products have not been assessed. Objectives To identify the hair dye substances presently used in non-oxidative hair dye products in Europe. Methods Ingredient label data on eligible products in 5 European countries were collected, and 289 different non-oxidative hair dye products were included in this study. Results Up to 9 hair dye substances were present in each product. Sixty-eight individual hair dye substances were identified on the 289 product labels, and their occurrence ranged from 0.3% to 34%. There were differences concerning substances used and their number per product between products of different consistency and colour. Conclusions The hair dye substances in non-oxidative hair dye products are different from those in oxidative hair dye products, and are currently not covered by patch test series. The toxicological and skin-sensitizing profile of the substances in non-oxidative hair dye products, as well as their concentrations, should be further investigated.

Peer-reviewed., A revised risk assessment for toxaphene was developed, based on the assumption that fish consumers are only exposed to toxaphene residues that differ substantially from technical toxaphene due to environmental degradation and metabolism. In vitro studies confirmed that both technical toxaphene and degraded toxaphene inhibit gap junctional intercellular communication that correlates with the mechanistic potential to cause tumour promotion. In vivo rat studies established the NOAEL for degraded and technical toxaphene at the highest dose tested in the bioassay. Toxaphene residue intakes from European fishery products were estimated and compared to the provisional tolerable daily intakes (TDIs) from various regulatory agencies including Canada, the United States, Germany. The estimated intake was also compared to a new calculated provisional MATT pTDI. The MATT pTDI is based upon new toxicological information (in vivo rat studies) developed on a model for environmental toxaphene residues rather than technical toxaphene. A MATT pTDI (1.08 mg total toxaphene for a person of 60 kg) for tumour promotion potency was adopted for use in Europe and is hitherto referred to as the MATT pTDI. These new data result in a better estimate of safety and a higher TDI than previously used. Based on realistic fish consumption data and recent baseline concentration data of toxaphene in European fishery products the toxaphene intake for the consumers of Germany, Ireland, Norway and The Netherlands was estimated. For an average adult fish consumer the average daily intake of toxaphene was estimated to be 1.2 µg, and 0.4, 0.5, and 0.2 µg for the consumers of Norway, Germany, Ireland, and The Netherlands, respectively. The toxaphene intake of these average fish consumers was far below the MATT pTDI of 1.08 mg/60 kg body weight. In conclusion, based on the most relevant toxicological studies and the most realistic estimates of fish consumption and recent concentrations of toxaphene in European fishery products, adverse health effects are unlikely for the average European consumer of fishery products. In no case is the MATT pTDI exceeded.

The impact of endocrine disruptors, and specifically the low-dose issue, involves interdisciplinary sciences. Thus, in the past these topics have been published widely in the toxicology area. Owing to recent developments in biology, including the whole-genome reading program, the mechanisms underlying the low-dose issue have been clarified. These mechanisms have been found to involve stochastic and probabilistic receptor-mediated adverse effects induced by endocrine disruptors. The effects thought to be induced by low doses of endocrine-disrupting chemicals remain disputed, and the underlying mechanisms remain poorly understood. Three independent factors, each only recently identified and never before encountered in the history of toxicological studies, are associated with what is termed the ‘low-dose issue’. First, toxicological risk has been estimated only by extrapolation of adverse phenotypes from high-dose effects and thus provides no reliable information on low-dose effects observed at the right time under experimental paradigm with sufficient sensitivity. Second, toxicity is based on disturbances of homeostatic regulation, a largely unexplored area in toxicology. Third, toxicity is based on stochastic and probabilistic xenobiotic response, a new field of toxicology that is specifically linked to low-dose and less-frequent events. To resolve the low-dose issue whether it causes effects or whether effects observed at low-doses should be considered ‘adverse’ – or both, each of these factors needs to be addressed. Copyright © 2010 John Wiley & Sons, Ltd.

A method for the objective measurement of light dissemination in the lens was developed. There is an exponential relationship between the concentration of standard solutions and the intensity of light disseminated forwards. The light disseminated in non-pathological lenses from Sprague Dawley rats was registered as the equivalent standard concentration, C, and then transformed to log10 (C + 1) and was found not to deviate from the normal distribution. The tolerance limit for light dissemination was derived by setting the probability to classify a non-pathological lens as pathological. An analysis of variance demonstrated that the inter-animal variation was the dominating source of imprecision. It is anticipated that the developed system will be useful in experimental toxicological risk assessment.

Calculating risk is relatively straightforward when there is reliable statistical evidence on which to base a judgment. However, novel technologies are often characterised by a lack of such historical data, which creates a problem for risk assessment. In fact, numerical risk assessments can be positively misleading in such situations. We describe a decision support system – StAR – that gives quantitative assessments where appropriate, but which is also able to provide qualitative risk assessments based on arguments for and against the presence of risk. The user is presented with a summary statement of risk, together with the arguments that underlie this assessment. Furthermore, the user is able to search beyond these top-level arguments in order to discover more about the available evidence. Here we suggest that this approach is well-suited to the way in which people naturally make decisions, and we show how the StAR approach has been implemented in the domain of toxicological risk assessment.

1,3-Dimethyl 2-imidazolidinone (DMI) is of lower toxicological risk than 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (DMPU), hexamethyl-phosphorus triamide (HMPT), and hexamethylphosphoramid...

The chronic toxicity is fundamental for toxicological risk assessment, but its correlation with the chemical structures has been studied only little. This is partly due to the complexity of such an experimental test that embraces a plethora of different biological effects and mechanisms of action, making (Q)SAR studies extremely challenging. In this paper we report a predictive in silico study of more than 400 compounds based on two-dimensional chemical descriptors and multivariate analysis. The root mean squared error of the predictive model is 0.73 (in a logarithmic scale) on a leave-one-out cross-validation and is close to the estimated variability of experimental values (0.64). The analysis of the model revealed that the chronic toxicity effects are driven by the bioavailability of the compound that constitutes a baseline effect plus excess toxicity possible described by a few chemical moieties. The results obtained give confidence that this model can be useful for establishing a level of safety conce...

Curcuma longa L. (syn C. domestica Val.) rhizomes were extracted with ethyl acetate; the miscella was partially desolventized and the curcuminoids precipitated at ca 25° C. The work-up afforded pigments in 2.77% yield with colour value 14300 equivalent to 90.42% curcumin and demonstrated the use of ethyl acetate, which has a benign toxicological profile, for the recovery of the turmeric colourant.