EFSA’s toxicological assessment of aspartame: was it even-handedly trying to identify possible unreliable positives and unreliable negatives?

PMID: 

Arch Public Health. 2019 ;77:34. Epub 2019 Jul 15. PMID: 31338189

Abstract Title: 

EFSA's toxicological assessment of aspartame: was it even-handedly trying to identify possible unreliable positives and unreliable negatives?

Abstract: 

Background: A detailed appraisal is provided of the most recent (December 2013) assessment of the safety and/or toxicity of the artificial sweetener aspartame by the European Food Safety Authority's Panel on Food Additives and Nutrient Sources Added to Food. That appraisal is prefaced with a contextualising chronological account drawn from a documentary archive of the key highlights of the antecedent scientific and policy debates concerning this sweetener from the early 1970s onwards. The appraisal focuses specifically on Section 3.2 of the panel's review, which is headed 'Toxicological data of aspartame'.Methods: The methodology of the appraisal focusses on the extent to which the panel was symmetrically alert to possible false positives and false negatives, which in toxicological terms denote misleading indications of possible toxicity or misleading indications of safety. The methodology involved identifying and tabulating the prima facie indications of each of 154 empirical studies, and then comparing them with the way in which the panel chose to interpret the studies' findings, by focussing primarily on whether the panel deemed those studies to be reliable or unreliable. If the panel had been even-handed, the criteria for assessing reliability should have been the same for both putative positive and negative studies.Results: Eighty-one studies were identified that prima facie did not indicate any possible harm, and of those the panel deemed 62 to be reliable and 19 as unreliable. Seventy-three studies were identified that prima facie did indicate possible harm; of those the panel deemed all 73 to be unreliable; none were deemed reliable. A qualitative comparative review of the criteria of appraisal invoked by the panel to judge the reliability of putative negative and positive studies is also provided.Conclusion: The quantitative result indicate that the panel's appraisal of the available studies was asymmetrically more alert to putative false positives than to possible false negatives. The qualitative analysis shows that very demanding criteria were used to judge putative positive studies, while far more lax and forgiving criteria were applied to putative negative studies.Discussion: That quantitative and qualitative patterns are very problematic for a body supposed to prioritise the protection of public health. Given the shortcomings of EFSA's risk assessment of aspartame, and the shortcomings of all previous official toxicological risk assessments of aspartame, it would be premature to conclude that it is acceptably safe. They also imply that the manner in which EFSA panels operate needs to be scrutinised and reformed.

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Exposure to very low doses of a mixture of chemicals induces genotoxic effects as well as monotonic cytotoxic effects in a tissue-dependent manner.

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PMID: 

Toxicol Lett. 2019 Sep 12. Epub 2019 Sep 12. PMID: 31521832

Abstract Title: 

Genotoxic, cytotoxic, and cytopathological effects in rats exposed for 18 months to a mixture of 13 chemicals in doses below NOAEL levels.

Abstract: 

The present study investigates the genotoxic and cytotoxic effects of long term exposure to low doses of a mixture consisting of methomyl, triadimefon, dimethoate, glyphosate, carbaryl, methyl parathion, aspartame, sodium benzoate, EDTA, ethylparaben, buthylparaben, bisphenol A and acacia gum in rats. Four groups of ten Sprangue Dawley rats (5 males and 5 females per group) were exposed for 18 months to the mixture in doses of 0xNOAEL, 0.0025xNOAEL, 0.01xNOAEL and 0.05xNOAEL (mg/kg bw/day). After 18 months of exposure, the rats were sacrificed and their organs were harvested. Micronuclei frequency was evaluated in bone marrow erythrocytes whereas the organs were cytopathologically examined by the touch preparation technique. The exposure to the mixture caused a genotoxic effect identified only in females. Cytopathological examination showed specific alterations of tissue organization in a tissue-type dependent manner. The observed effects were dose-dependent and correlated to various tissue parameters. Specifically, testes samples revealed degenerative and cellularity disorders, liver hepatocytes exhibited decreased glycogen deposition whereas degenerative changes were present in gastric cells. Lung tissue presented increased inflammatory cells infiltration and alveolar macrophages with enhanced phagocytic activity, whereas brain tissue exhibited changes in glial and astrocyte cells' numbers. In conclusion, exposure to very low doses of the tested mixture for 18 months induces genotoxic effects as well as monotonic cytotoxic effects in a tissue-dependent manner.

Artificial sweeteners cause cytoplasmic fatty change of varying degrees.

PMID: 

J Coll Physicians Surg Pak. 2019 Sep ;29(9):848-851. PMID: 31455480

Abstract Title: 

Aspartame and Sucralose-induced Fatty Changes in Rat Liver.

Abstract: 

OBJECTIVE: To determine the cytoplasmic fatty change of rat liver due to artificial sweeteners – aspartame and sucralose.STUDY DESIGN: Experimental study.PLACE AND DURATION OF STUDY: Department of Anatomy, King Edward Medical University, Lahore, in collaboration with the University of Veterinary and Animal Sciences Lahore, from May to October 2016.METHODOLOGY: Adult Wistar albino rats were randomly divided into five groups. Group I was control group (animals were given drinking water by oral gavage). The animals of group II and III were given low (40 mg/kg body weight) and high dose (1000 mg/kg body weight) of aspartame, respectively. Animals of group IV and V were given low (5 mg/kg body weight) and high dose (1000 mg/kg body weight) of sucralose respectively by oral gavage. Doses were given once daily, six days a week for a total duration of 8 weeks. At the end of experiment, livers of all animal groups were observed for fatty change of cytoplasm.RESULTS: Artificial sweeteners cause cytoplasmic fatty change of varying degrees. This change was more marked in high dose group of aspartame (group III) as compared to low dose group (group II). In sucralose group, this change was seen only in high dose group (group V).CONCLUSION: Both artificial sweeteners-induced fatty changes in rat liver; the effect was least pronounced with low dose of sucralose.

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The artificial sweetener Splenda intake promotes changes in expression of c-Fos and NeuN in hypothalamus and hippocampus of rats.

PMID: 

Brain Res. 2018 12 1 ;1700:181-189. Epub 2018 Sep 7. PMID: 30201258

Abstract Title: 

The artificial sweetener Splenda intake promotes changes in expression of c-Fos and NeuN in hypothalamus and hippocampus of rats.

Abstract: 

BACKGROUND: Obesity is the result of the interaction of multiple variables, including the excessive increase of sugar-sweetened beverages consumption. Diets aimed to treat obesity have suggested the use of artificial sweeteners. However, recent evidence has shown several health deficits after intake of artificial sweeteners, including effects in neuronal activity. Therefore, the influence of artificial sweeteners consumption such as Splenda, on the expression of c-Fos and neuronal nuclear protein (NeuN) in hypothalamus and hippocampus remains to be determined.OBJECTIVES: We investigated the effects on c-Fos or NeuN expression in hypothalamus and hippocampus of Splenda-treated rats.METHODS: Splenda was diluted in water (25, 75 or 250 mg/100 mL) and orally given to rats during 2 weeks ad libitum. Next, animals were sacrificed by decapitation and brains were collected for analysis of c-Fos or NeuN immunoreactivity.RESULTS: Consumption of Splenda provoked an inverted U-shaped dose-effect in c-Fos expression in ventromedial hypothalamic nucleus while similar findings were observed in dentate gyrus of hippocampus. In addition, NeuN immunoreactivity was enhanced in ventromedial hypothalamic nucleus at 25 or 75 mg/100 mL of Splenda intake whereas an opposite effect was observed at 250 mg/100 mL of artificial sweetener consumption. Lastly, NeuN positive neurons were increased in CA2/CA3 fields of hippocampus from Splenda-treated rats (25, 75 or 250 mg/100 mL).CONCLUSION: Consuming Splenda induced effects in neuronal biomarkers expression. To our knowledge, this study is the first description of the impact of intake Splenda on c-Fos and NeuN immunoreactivity in hypothalamus and hippocampus in rats.

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Selenium-enriched radish sprouts could be developed into an effective food and health care product for the liver injury prevention.

PMID: 

J Food Sci. 2019 Sep 17. Epub 2019 Sep 17. PMID: 31529805

Abstract Title: 

Protective Effect of Selenium-Enriched Red Radish Sprouts on Carbon Tetrachloride-Induced Liver Injury in Mice.

Abstract: 

This study aimed to investigate the effect of Se (Selenium) treatment on nutritional quality in radish sprouts. The results showed that 15µM sodium selenite significantly increased phenolics compounds, flavonoids compounds, anthocyanins, and some essential amino acid content, while improving the total antioxidant capacity of radish sprouts. Besides, the Se-enriched radish sprouts significantly alleviated the liver damage caused by carbon tetrachloride (CCl) in mice and improved the antioxidant capacity of the liver in mice, whereas the Se-enriched radish sprouts alleviated the inflammatory reaction and apoptosis caused by CCl. These results imply that Se-enriched radish sprouts have a positive impact on mice with CCl-induced liver injury, and that in future Se-enriched radish sprouts could be developed into an effective food and health care product for the liver injury prevention. PRACTICAL APPLICATION: Because selenium is an essential trace element in the human body, selenium-enriched sprouts can help eliminate free radicals in the body, relieve aging, and selenium-deficient diseases. They are easy to grow and have low costs. Hence, selenium-enriched sprouts have a great potential of being widely consumed.

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Acetaminophen is increasingly present in the natural water environment.

PMID: 

Chemosphere. 2019 Jul 22 ;236:124391. Epub 2019 Jul 22. PMID: 31545194

Abstract Title: 

Acetaminophen micropollutant: Historical and current occurrences, toxicity, removal strategies and transformation pathways in different environments.

Abstract: 

Acetaminophen (ACT) is commonly used as a counter painkiller and nowadays, it is increasingly present in the natural water environment. Although its concentrations are usually at the ppt to ppm levels, ACT can transform into various intermediates depending on the environmental conditions. Due to the complexity of the ACT degradation products and the intermediates, it poses a major challenge for monitoring, detection and to propose adequate treatment technologies. The main objectives of this review study were to assess (i) the occurrences and toxicities, (2) the removal technologies and (3) the transformation pathways and intermediates of ACT in four environmental compartments namely wastewater, surface water, ground water, and soil/sediments. Based on the review, it was observed that the ACT concentrations in wastewater can reach up to several hundreds of ppb. Amongst the different countries, China and the USA showed the highest ACT concentration in wastewater (≤300 μg/L), with a very high detection frequency (81-100%). Concerning surface water, the ACT concentrations were found to be at the ppt level. Some regions in France, Spain, Germany, Korea, USA, and UK comply with the recommended ACT concentration for drinking water (71 ng/L). Notably, ACT can transform and degrade into various metabolites such as aromatic derivatives or organic acids. Some of them (e.g., hydroquinone and benzoquinone) are toxic to human and other life forms. Thus, in water and wastewater treatment plants, tertiary treatment systems such as advanced oxidation, membraneseparation, and hybrid processes should be used to remove the toxic metabolites of ACT.

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Chemical and physical changes of microplastics during sterilization by chlorination.

PMID: 

Water Res. 2019 Oct 15 ;163:114871. Epub 2019 Jul 15. PMID: 31351353

Abstract Title: 

Chemical and physical changes of microplastics during sterilization by chlorination.

Abstract: 

Wastewater treatment plants are known to release microplastics that have been detected in aquatic and terrestrial organisms constituting part of the human diet. Chlorination of wastewater-borne microplastics was hypothesized to induce chemical and physical changes detectable by Raman spectroscopy and differential scanning calorimetry (DSC). In the laboratory, virgin plastics (∼0.05 × 2 × 2 mm) were exposed to differing sterilization conditions representative of dosages used in the disinfection of drinking water, wastewater, and heavily contaminated surfaces. Polypropylene (PP) was most resistant to chlorination, followed by high density polyethylene (HDPE)and polystyrene (PS). Polystyrene showed degradation, indicated by changes in Raman peak widths, at concentration-time regimes (CT values) as low as 75 mg min/L, whereas HDPE and PP remained unaltered even at chlorine doses characteristic of wastewater disinfection (150 mg min/L). However, HDPE and PS were not completely resistant to oxidative attack by chlorination. Under extremely harsh conditions, shifts in Raman peaks and the formation of new bonds were observed. These results show that plastics commonly used in consumer products can be chemically altered, some even under conditions prevailing during wastewater treatment. Changes in polymer properties, observed for HDPE and PP under extreme exposure conditions only, are predicted to alter the risk microplastics pose to aquatic and terrestrial biota, since an increase in carbon-chlorine (C-Cl) bonds is known to increase toxicity, rendering the polymers more hydrophobic and thus more prone to adsorb, accumulate, and transport harmful persistent pollutants to biota in both aquatic and terrestrial environments.

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Human consumption of microplastics.

PMID: 

Environ Sci Technol. 2019 06 18 ;53(12):7068-7074. Epub 2019 Jun 5. PMID: 31184127

Abstract Title: 

Human Consumption of Microplastics.

Abstract: 

Microplastics are ubiquitous across ecosystems, yet the exposure risk to humans is unresolved. Focusing on the American diet, we evaluated the number of microplastic particles in commonly consumed foods in relation to their recommended daily intake. The potential for microplastic inhalation and how the source of drinking water may affect microplastic consumption were also explored. Our analysis used 402 data points from 26 studies, which represents over 3600 processed samples. Evaluating approximately 15% of Americans' caloric intake, we estimate that annual microplastics consumption ranges from 39000 to 52000 particles depending on age and sex. These estimates increase to 74000 and 121000 when inhalation is considered. Additionally, individuals who meet their recommended water intake through only bottled sources may be ingesting an additional 90000 microplastics annually, compared to 4000 microplastics for those who consume only tap water. These estimates are subject to large amounts of variation; however, given methodological and data limitations, these values are likely underestimates.

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Anthropogenic contaminants of high concern: Existence in water resources and their adverse effects.

PMID: 

Sci Total Environ. 2019 Nov 10 ;690:1068-1088. Epub 2019 Jul 6. PMID: 31470472

Abstract Title: 

Anthropogenic contaminants of high concern: Existence in water resources and their adverse effects.

Abstract: 

Existence of anthropogenic contaminants (ACs) in different environmental matrices is a serious and unresolved concern. For instance, ACs from different sectors, such as industrial, agricultural, and pharmaceutical, are found in water bodies with considerable endocrine disruptors potency and can damage the biotic components of the environment. The continuous ACs exposure can cause cellular toxicity, apoptosis, genotoxicity, and alterations in sex ratios in human beings. Whereas, aquatic organisms show bioaccumulation, trophic chains, and biomagnification of ACs through different entry route. These problems have been found in many countries around the globe, making them a worldwide concern. ACs have been found in different environmental matrices, such as water reservoirs for human consumption, wastewater treatment plants (WWTPs), drinking water treatment plants (DWTPs), groundwaters, surface waters, rivers, and seas, which demonstrate their free movement within the environment in an uncontrolled manner. This work provides a detailed overview of ACs occurrence in water bodies along with their toxicological effect on living organisms. The literature data reported between 2017 and 2018 is compiled following inclusion-exclusion criteria, and the obtained information was mapped as per type and source of ACs. The most important ACs are pharmaceuticals (diclofenac, ibuprofen, naproxen, ofloxacin, acetaminophen, progesterone ranitidine, and testosterone), agricultural products or pesticides (atrazine, carbendazim, fipronil), narcotics and illegal drugs (amphetamines, cocaine, and benzoylecgonine), food industry derivatives (bisphenol A, and caffeine), and personal care products (triclosan, and other related surfactants). Considering this threatening issue, robust detection and removal strategies must be considered in the design of WWTPs and DWTPs.

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The study indicated that the current esophageal cancer mortality rate was mainly caused by water pollution from the previous 8 years.

PMID: 

Environ Sci Pollut Res Int. 2019 Sep 9. Epub 2019 Sep 9. PMID: 31502054

Abstract Title: 

The lag effect of water pollution on the mortality rate for esophageal cancer in a rapidly industrialized region in China.

Abstract: 

The Huai River basin (located in eastern China) has a population of 180 million and has the highest risk of esophageal cancer (EC) mortality in China. Some studies found that contaminants in drinking water are a major risk factor for cancers of the digestive system. However, the effect of water pollution in the historical period on the current EC mortality remains unclear. Data were collected on the EC mortality rate in 2004 in the Huai River basin in 11 counties, and data on the surface water quality in the region from 1987 to 2004 were used. The Pearson correlation and the GeoDetector q-statistic were employed to explore the association between water pollution and the EC mortality rate in different lag periods, from linear and nonlinear perspectives, respectively. The study showed apparently spatial heterogeneity of the EC mortality rate in the region. The EC mortality rate downstream is significantly higher than that in other regions; in the midstream, the region north of the mainstream has a lower average mortality rate than that south of the area. Upstream, the region north of the mainstream has a higher mortality rate than that in the southern area. The spatial pattern was formed under the influence of water pollution in the historical period. 1996, 1997, and 1998 have the strongest linear or nonlinear effect on the EC mortality rate in 2004, in which the Pearson correlation coefficient and the q-statistic were the highest, 0.79 and 0.89, respectively. Rapid industrialization in the past 20 years has caused environmental problems and poses related health risks. The study indicated that the current EC mortality rate was mainly caused by water pollution from the previous 8 years. The findings provide knowledge about the lag time for pollution effects on the EC mortality rate, and can contribute to the controlling and preventing esophageal cancer.

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