Work-related and personal risk factors for occupational contact dermatitis: A systematic review of the literature with meta-analysis.

The objective of this review is to identify work-related and personal risk factors for contact dermatitis (CD), and assess their association with this frequently occurring occupational disease. A systematic review of the literature from 1990 to June 2, 2020, was conducted using Medline and Embase. Prospective cohort and case-control studies were included, and meta-analyses were conducted when feasible. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation. Twenty-nine studies were identified, comprising 26 study populations and with a total of 846 209 participants investigating 52 risk factors for CD. Meta-analyses were performed for five risk factors, all of them for irritant contact dermatitis (ICD). Moderate-quality evidence was found for associations between wet work and ICD (OR: 1.56, 95%CI: 1.21-2.01). High-quality evidence was found for the association between atopic dermatitis and ICD (OR: 2.44, 95%CI: 1.89-3.15). There was no evidence for an association between ICD and sex or history of hand dermatitis, respiratory and mucosal atopy. In conclusion, several work-related and personal risk factors associated with CD were identified. Our data emphasize the need for the assessment of both, work-related and personal, risk factors to prevent occupational CD.

Overview of available toxicity data for calystegines.

Calystegines are polyhydroxylated nortropane alkaloids that have been found in various solanaceous foods, in particular in potatoes and aubergines. The biological activity and potential toxicity of calystegines are associated with their capacity to inhibit glycosidases and block carbohydrate metabolism inducing lysosomal storage toxicity. The present report summarises the retrieved information on the possible toxicity of calystegines. Only few in vivo short-term toxicological studies in rodents on individual calystegines or mixtures of calystegines were retrieved. Overall, these studies are insufficient to conclude on the possible chronic toxicity effects of calystegines in humans, in particular considering the short duration of the studies and potential lower sensitivity of rats and mice to glycosidase inhibitors, compared to other species such as goats and guinea pigs. Several studies and case reports were retrieved on the toxic effects induced in livestock or experimental animals following consumption or administration of plants containing calystegines. However, the concurrent presence of other alkaloids, in particular swainsonine, did not allow using these studies to draw conclusions on the toxicity of calystegines. Since no experimental data on genotoxicity of calystegines were retrieved, in silico predicting models were applied to identify possible alert for genotoxicity of five calystegines recently detected in food. In most of the cases, the outcome of the computational predictions indicated no alerts for genotoxicity; however, the low reliability of the results prevents a firm conclusion on the genotoxic potential of the substances. Overall, the available data do not allow drawing conclusions on the possible toxic effects of calystegines in humans or in livestock, and more data in relevant experimental models would be necessary to characterise the toxic profile of this group of substances.

Update of the Scientific Opinion on opium alkaloids in poppy seeds.

Poppy seeds are obtained from the opium poppy (Papaver somniferum L.). They are used as food and to produce edible oil. The opium poppy plant contains narcotic alkaloids such as morphine and codeine. Poppy seeds do not contain the opium alkaloids, but can become contaminated with alkaloids as a result of pest damage and during harvesting. The European Commission asked EFSA to provide an update of the Scientific Opinion on opium alkaloids in poppy seeds. The assessment is based on data on morphine, codeine, thebaine, oripavine, noscapine and papaverine in poppy seed samples. The CONTAM Panel confirms the acute reference dose (ARfD) of 10 µg morphine/kg body weight (bw) and concluded that the concentration of codeine in the poppy seed samples should be taken into account by converting codeine to morphine equivalents, using a factor of 0.2. The ARfD is therefore a group ARfD for morphine and codeine, expressed in morphine equivalents. Mean and high levels of dietary exposure to morphine equivalents from poppy seeds considered to have high levels of opium alkaloids (i.e. poppy seeds from varieties primarily grown for pharmaceutical use) exceed the ARfD in most age groups. For poppy seeds considered to have relatively low concentrations of opium alkaloids (i.e. primarily varieties for food use), some exceedance of the ARfD is also seen at high levels of dietary exposure in most surveys. For noscapine and papaverine, the available data do not allow making a hazard characterisation. However, comparison of the dietary exposure to the recommended therapeutical doses does not suggest a health concern for these alkaloids. For thebaine and oripavine, no risk characterisation was done due to insufficient data. However, for thebaine, limited evidence indicates a higher acute lethality than for morphine and the estimated exposure could present a health risk.

Chronic 14-day exposure to insecticides or methylmercury modulates neuronal activity in primary rat cortical cultures.

There is an increasing demand for in vitro test systems to detect neurotoxicity for use in chemical risk assessment. In this study, we evaluated the applicability of rat primary cortical cultures grown on multi-well micro-electrode arrays (mwMEAs) to detect effects of chronic 14-day exposure to structurally different insecticides or methylmercury on neuronal activity (mean spike rate; MSR). Effects of chronic exposure to α-cypermethrin, endosulfan, carbaryl, chlorpyrifos(-oxon), methylmercury or solvent control [14days exposure, initiated after baseline recording at day in vitro (DIV)7] were studied in five successive recordings between DIV10 and DIV21. The results were compared to effects of acute exposure to these same compounds (activity recorded immediately after the start of exposure after baseline recording at DIV10-11). Chronic 14-day exposure to methylmercury, chlorpyrifos and α-cypermethrin inhibited MSR, all with a lowest-observed effect concentration (LOEC) of 0.1µM, while exposure to endosulfan increased MSR [LOEC: 1µM]. No significant effects were observed for chlorpyrifos-oxon and carbaryl. Similar to the observations in the chronic 14-day exposure studies, MSR was inhibited by acute 30-min exposure to methylmercury, chlorpyrifos, and α-cypermethrin [LOECs: 1µM, 10µM, and 1µM, respectively], whereas endosulfan increased MSR [LOEC: 0.3µM]. While not observed in the chronic 14-day exposure study, acute exposure to chlorpyrifos-oxon and carbaryl resulted in inhibition of MSR [LOECs: 10µM, and100 µM, respectively]. Effects on median interspike intervals (mISI; a measure for neuronal firing pattern) were not detected following chronic 14-day or acute 30-min exposure, except for increased mISI at acute chlorpyrifos and α-cypermethrin exposures at concentrations that also inhibited MSR. These data indicate that the effects of chronic 14-day exposures to methylmercury and insecticides at low concentrations on spontaneous neuronal activity in vitro can be predicted in rapid acute screening studies using mwMEAs.