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The safety assessment of pentylene glycol (PG) has been based on a bioavailability extrapolated from those of other 1,2-glycols or an assumed 100% absorption. To make a better safety assessment and an accurate calculation of the margin of safety (MoS), the skin penetration of PG present in a commercially available sunscreen was measured in pig skin at different exposure durations. The mass balance of PG decreased with increasing exposure durations, from 98% (1 h) to 29% (24 h) and the amount of PG detected in the skin wash decreased over time from 93% to 3%. The decrease in mass balance was attributed to an unexpected volatility of PG, which was confirmed in additional experiments. The maximum bioavailable amount of PG was 123 μg/cm2 after 24 h and was considered to be worst case scenario (10 mg/cm 2 i.e. 5-fold the recommended application standard dose, 2 mg/cm 2 ). MoS values for the application of a standard dose of sunscreen after 1–24 h exposure were 140–671 in adults and, if calculated for children ratios, 87–217 Based on the available toxicological data for PG in comparison to the amounts determined to be potentially bioavailable, PG in the test sun protection product SPF 50 + does not show any safety concerns for daily usage at the recommended dosage of 2 mg/cm 2 or lower. [ABSTRACT FROM AUTHOR]

A physiologically-based pharmacokinetic (PBPK) model (Schroeter et al., 2011) was applied to simulate target tissue manganese (Mn) concentrations following occupational and environmental exposures. These estimates of target tissue Mn concentrations were compared to determine margins of safety (MOS) and to evaluate the biological relevance of applying safety factors to derive acceptable Mn air concentrations. Mn blood concentrations measured in occupational studies permitted verification of the human PBPK models, increasing confidence in the resulting estimates. Mn exposure was determined based on measured ambient air Mn concentrations and dietary data in Canada and the United States (US). Incorporating dietary and inhalation exposures into the models indicated that increases in target tissue concentrations above endogenous levels only begin to occur when humans are exposed to levels of Mn in ambient air (i.e. > 10 μg/m 3 ) that are far higher than those currently measured in Canada or the US. A MOS greater than three orders of magnitude was observed, indicating that current Mn air concentrations are far below concentrations that would be required to produce the target tissue Mn concentrations associated with subclinical neurological effects. This application of PBPK modeling for an essential element clearly demonstrates that the conventional application of default factors to “convert” an occupational exposure to an equivalent continuous environmental exposure, followed by the application of safety factors, is not appropriate in the case of Mn. PBPK modeling demonstrates that the relationship between ambient Mn exposures and dose-to-target tissue is not linear due to normal tissue background levels and homeostatic controls. [ABSTRACT FROM AUTHOR]

The concentrations of nine metals (Cd, Pb, Ni, Cr, Co, Cu, Fe, Mn and Zn) were measured in selected brands of medicated, moisturizing and skin-lightening soaps and shower gels with the aim of evaluating the human health risk associated with metal exposure from the use of these products. The concentrations of metals in these products were determined by means of atomic absorption spectrophotometry after sample digestion with a mixture of acids. The concentration ranges of the metals in the bathing soaps and shower gels were found to be: <0.06–3.4 μg g −1 for Cd, <0.09–26.5 μg g −1 for Pb, <0.12–43.0 μg g −1 for Cr, <0.06–32.5 μg g −1 for Ni, <0.06–40.5 μg g −1 for Cu, <0.12–8.0 μg g −1 for Co, 61.8–4000 μg g −1 for Fe, <0.09–29.5 μg g −1 for Mn, and 25.5–1000 μg g −1 for Zn. The systemic exposure dosage values for these metals obtained from the application of these brands of bathing soaps and shower gels were below their respective provisional tolerable daily intake/or recommended daily intake values. The margin of safety values obtained for the metals were greater than 100 which indicated that there was no significant risk to the users of these brands of bathing soaps and shower gels, except in the case of Co. [ABSTRACT FROM AUTHOR]

Hair dye products include a range of chemicals, depending on the type and color. A common primary intermediate compound used to achieve the permanent effect of hair dye is para-phenylenediamine (PPD). 4-aminobiphenyl (4-ABP) has reportedly been found as a trace contaminant (presumably from the para-phenylenediamine [PPD] ingredient) in consumer permanent hair dye. While several regulatory agencies have designated 4-ABP as a human bladder carcinogen based on evidence in humans and experimental animals, only the Office of Environmental Health Hazard Assessment (OEHHA) have established a cancer risk value for 4-ABP of 0.03 μg/day based on liver tumors developed in mice. A hypothetical dermal risk assessment was performed to estimate the bladder cancer risk associated with exposure to 4-ABP from personal use of permanent hair dye potentially containing incidental 4-ABP. Previously published laboratory analyses characterizing 4-ABP concentrations in consumer hair dyes indicate the concentrations can range from below the limit of detection to 8120 ppb. Precautionary estimates of human scalp surface area, maximum skin adherence, hair dye retention factor, and percent dermal absorption were used to estimate the daily systemic exposure doses (SEDs) from dermal application of hair dye. The estimated SEDs ranged from 0.05 to 3000 pg/day. A margin of safety (MOS) was calculated as the ratio of the NSRL to the SED and ranged from 10 to 570,000. The results of this study suggest that there is no indication of increased risk of bladder cancer in humans from exposure to 4-ABP in consumer hair dye, especially as it is extremely unlikely that a consumer would use permanent hair dye on a daily basis (as this assessment models). • 4-ABP has reportedly been found as a trace contaminant in permanent hair dye. • Assess whether dermal exposure to 4-ABP in hair dye increases risk of bladder cancer. • Application of contaminated hair dye would not increase the risk of bladder cancer. [ABSTRACT FROM AUTHOR]

Quaternary ammonium compounds (QACs) are widely used in consumer products because of their unique antibacterial properties, and dishwashing detergents are a major source of exposure through oral, inhalation, and dermal routes. The three classes of QACs, including benzalkonium chloride (BAC), n -alkyldimethylethylbenzylammonium chloride (ADEBAC), and di- n -alkyldimethylammonium chloride (DDAC), in spray and non-spray types of dishwashing detergents were quantified by high-performance liquid chromatography-mass spectrometry. A tiered risk assessment approach was also considered. In the Tier 1 assessment, the mean and worst-case exposure were estimated to screen for rough exposure and risk levels. In the Tier 2 assessment, mean and upper-tail exposure levels were calculated based on the exposure parameters of Korean consumers using Monte Carlo simulation. QACs had a low frequency of detection of up to 20% in dishwashing detergents, and the contents of detected QACs varied depending on the individual samples. Based on the results of the Tier 1 assessment, BACs and DDACs posed potential health risks via inhalation and dermal routes. Tier 2 assessment suggested that the current level of oral and dermal exposure of Korean consumers to QACs in dishwashing detergents is unlikely to pose a health risk, even for upper-tail exposure groups. However, the present results suggest that spray-type DDACs may pose a health risk in the upper-tail inhalation exposure group, and further investigation is required to clarify this risk. [Display omitted] • Quaternary ammonium compounds (BAC/ADEBAC/DDAC) in 55 dishwashing detergents were tested. • BACs and DDACs were found, but ADEBACs were not detected in dishwashing detergents. • Current risk levels of BAC and DDAC were determined via two-step tiered assessment. • From Tier 1 assessment, BACs and DDACs pose health risks via inhalation and dermal exposure. • From Tier 2 assessment, DDACs pose risks to upper-tail inhalation exposure group. [ABSTRACT FROM AUTHOR]

Economic escape theory that predicts that flight initiation distance (FID=predator-prey distance when a prey begins to flee from an approaching predator) increases as predation risk increases has been overwhelmingly supported. However, the vast majority of empirical tests have focused on effects of single predation risk factors. Even studies that have included multiple risk factors have not predicted how they jointly affect FID. I present a model that predicts joint effects of several predation risk factors that affect the outcome of a race between predator and prey to the prey's refuge. As a prey's distance to refuge and predator attack speed increase, and as the prey's location forces it to flee more toward a predator to reach refuge, FID increases. A published model proposed and experiment showed that FID is longer when prey flee directly toward than directly away from a predator to a refuge. We present a new geometric model that predicts FID for all angles between the prey's and predator's paths to refuge, distance of the prey from refuge when escape begins, predator and prey speeds, and a margin of safety allowing the prey to reach refuge before the predator. The model provides many new, testable predictions about relationships among its variables and FID. Most notably, it predicts that FID increases sigmoidally as the angle between predator and prey paths to refuge increases. Although the model is not economic (cost-benefit), we discuss its relationship to economic escape theory. [ABSTRACT FROM AUTHOR]

Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is marketed on the Internet as a food supplement. The recommended intake is between 100 and 1400 mg per day. The substance is naturally occurring in raspberries (up to 4.3 mg/kg) and is used as a flavouring substance. Toxicological studies on raspberry ketone are limited to acute and subchronic studies in rats. When the lowest recommended daily dose of raspberry ketone (100 mg) as a food supplement is consumed, it is 56 times the established threshold of toxicological concern (TTC) of 1800 μg/day for Class 1 substances. The margin of safety (MOS) based on a NOAEL of 280 mg/kg bw/day for lower weight gain in rats is 165 at 100 mg and 12 at 1400 mg. The recommended doses are a concern taking into account the TTC and MOS. Investigations of raspberry ketone in quantitative structure-activity relationship (QSAR) models indicated potential cardiotoxic effects and potential effects on reproduction/development. Taking into account the high intake via supplements, the compound's toxic potential should be clarified with further experimental studies. In UK the pure compound is regarded as novel food requiring authorisation prior to marketing but raspberry ketone is not withdrawn from Internet sites from this country. [ABSTRACT FROM AUTHOR]

The concentrations of metals (Cd, Pb, Ni, Cr, Cu, Co, Fe, Mn, Zn and Al) were determined in thirty brands of popular of underarm cosmetics in Nigeria with a view to providing information on the levels of metals and the risk of exposure to metals by humans through long time usage of these products. The concentrations of metals in these samples of underarm cosmetics were measured by using atomic absorption spectrometry after acid digestion. The concentrations of metals in these types of underarm cosmetics studied ranged from <0.15 to 1.2 μg g −1 Cd, <0.02 to 11.2 μg g −1 Pb, <0.03 to 4.9 μg g −1 Ni, <0.1 to 25.0 μg g −1 , <0.02 to 2.8 μg g −1 Co, 2.0 to 6.4 μg g −1 Cu, 4.7 to 91.2 μg g −1 Fe, <0.05 to 14.1 μg g −1 Mn, 77.9 to 132 μg g −1 and 69.2 to 83,500 μg g −1 Al. The results of this study indicate that Cd, Pb, Ni, Cr and Co were presents in these types of underarm cosmetics at concentrations below the regulatory control limits for metal impurities in color additives for cosmetics and suggested limits following good manufacturing practice. The estimated margin of safety (MoS) indicated that the concentrations of the examined metals in these underarm cosmetic products present no potential risk to the users. The continuous use of these brands of underarm cosmetics represents a potential source of human exposure to metals such as aluminum in the local area of the breast, particularly to the upper outer quadrant. [ABSTRACT FROM AUTHOR]

Facial cosmetics are the most commonly consumed product, mainly by the women from all over the world irrespective of their age. The facial cosmetics may be contaminated with several toxic elements, which can get absorb on to the facial skin and migrate to the blood vessels. Hence the absorbed toxic elements can cause further adverse effects on the human body. The present study aims to assess the toxic element contents (arsenic, lead, nickel, mercury, and cadmium) in commonly consumed facial cosmetics (face powder, foundation, lightning creams, moisturizer, eye shadow, lipsticks, eyeliner, blush, mascara, sunscreen) and to carry out the risk assessment through different methods. The dermal risk was evaluated as SED, NOAEL, MoS, HQ and ILCR, which is linked with the exposure of selected toxic elements. The total CDDE for all selected elements in facial cosmetic products was found in increasing order as follow: face powder > foundation > lightning creams > moisturizer > eye shadow > lipsticks > eyeliner > blush > mascara > sunscreen. The HQ and HI values for selected elements were found to be < 1 in all facial cosmetics. Whereas the probable MoS of selected toxic elements in all facial cosmetics except eyeliner were found to be 3–4 folds lower than the minimum value of 100 regulated by the WHO. [Display omitted] • Dermal exposure to TEs in facial cosmetics is higher than permissible limit. • MoS for TEs in few facial cosmetics were 3–4 folds lower than minimum level. • Lower MoS values shows significant health concerns according to WHO. • HI values were found to be lower than 1 for all selected facial cosmetics. [ABSTRACT FROM AUTHOR]

Abstract: The margin of safety (MOS) approach is an increasingly prevalent tool for ensuring the integrity of market-based programs for providing ecosystem services. Over-crediting is reduced by setting aside mean estimates of uncertain services in favor of a more conservative estimate. Like many environmental policy problems, ecosystem service markets involve the aggregation of uncertainty over multiple scales, e.g. from landowners to market intermediaries to the overall market. We examine how the MOS instrument affects, and is affected by, an ecosystem services market. We show that the common bottom-up approach of imposing risk preferences at a local, disaggregated level—held over from earlier development in the context of toxics and command and control-style health risk regulation—leads to several unintended consequences. Furthermore, discounting landowner services can actually increase their profits, conditional on the elasticity of credit demand. We illustrate theoretical insights with an empirical application to greenhouse gas offset crediting in agriculture. [Copyright &y& Elsevier]

A Bayesian-updating approach is presented to the estimation of total uncertainty-based Margin of Safety (MOS) for Total Maximum Daily Load (TMDL) calculations. Probability distributions are presented to construct the likelihood function, the prior probability distribution, and the posterior (total uncertainty) probability distribution. The Bayesian-updating approach is demonstrated through a case study for the Lower Amite River, Louisiana. The posterior probability distribution-based on the Bayesian approach updates the standard deviation of summer dissolved oxygen in the Amite River from 1.88 mg/L to 2.10 mg/L when the total uncertainty is considered. Results from the Bayesian-updating approach are compared with two conventional methods. The dissolved oxygen reserve based on a conventional margin of safety of 20% is estimated to be 45,682.26 kg/Day. The second conventional method, where we consider the standard deviation of 1.88 mg/L, produces a dissolved oxygen reserve of 40,516.09 kg/Day. The Bayesian approach yields the dissolved oxygen reserve of 38,614.43 kg/Day with the first level (μ-σ) of MOS, producing a deficit of 5606.65 kg/Day in dissolved oxygen. The dissolved oxygen reserve deficit increases to 23,895.13 kg/Day when the second level (μ-2σ) of MOS is used, which escalated to 42,383.52 kg/Day when the highest level (μ-3σ) of MOS is used. While the total uncertainty-based Bayesian approach is demonstrated for a TMDL development on the Amite River, the overall approach could be applied in any river system with similar available data. [Copyright &y& Elsevier]

Abstract: The no-observed-adverse-effect-level (NOAEL) is an important part of the non-clinical risk assessment. It is a professional opinion based on the design of the study, indication of the drug, expected pharmacology, and spectrum of off-target effects. There is no consistent standard definition of NOAEL. This is based, in part, on the varied definitions of what constitutes an adverse effect. Toxicologists, either investigating or reviewing, have not been consistent in defining an effect as either adverse or acceptable. The common definition of NOAEL, “the highest experimental point that is without adverse effect,” serves us well in general discussions. It does not, however, address the interpretation of risk based on toxicologically relevant effects, nor does it consider the progression of effect with respect to duration and/or dose. This paper will discuss the issues and application of a functional definition of the NOAEL in toxicology evaluations. [Copyright &y& Elsevier]