Arsenic risk

Exposure to arsenic during embryogenesis impairs olfactory sensory neuron differentiation and function into adulthood.
Szymkowicz DB, Sims KC, Schwendinger KL, Tatnall CM, Powell RR, Bruce TF, Bridges WC, Bain LJ.
Toxicology. 2019 May 15;420:73-84. doi: 10.1016/j.tox.2019.04.005.

Nrf2 deficiency aggravates the increase in osteoclastogenesis and bone loss induced by inorganic arsenic.
Liu Z, Hou Y, Li L, Yang Y, Jia J, Hong Z, Li T, Xu Y, Fu J, Sun Y, Yamamoto M, Wang H, Pi J.
Toxicol Appl Pharmacol. 2019 Mar 15;367:62-70. doi: 10.1016/j.taap.2019.02.003. 

Arsenic accumulation in lettuce (Lactuca sativa L.) and broad bean (Vicia faba L.) crops and its potential risk for human consumption.
Yañez LM, Alfaro JA, Avila Carreras NME, Bovi Mitre G.
Heliyon. 2019 Jan 25;5(1):e01152. doi: 10.1016/j.heliyon.2019.e01152.

Inorganic arsenic induces pyroptosis and pancreatic β cells dysfunction through stimulating the IRE1α/TNF-α pathway and protective effect of taurine.
Pei P, Yao X, Jiang L, Qiu T, Wang N, Yang L, Gao N, Wang Z, Yang G, Liu X, Liu S, Jia X, Tao Y, Wei S, Sun X.
Food Chem Toxicol. 2019 Mar;125:392-402. doi: 10.1016/j.fct.2019.01.015. 

Impact of arsenic exposure on clinical biomarkers indicative of cardiovascular disease risk in Mexican women.
Ochoa-Martínez ÁC, Ruiz-Vera T, Almendarez-Reyna CI, Zarazúa S, Carrizales-Yáñez L, Pérez-Maldonado IN.
Ecotoxicol Environ Saf. 2019 Mar;169:678-686. doi: 10.1016/j.ecoenv.2018.11.088. 

Maternal arsenic exposure and nonsyndromic orofacial clefts.
Suhl J, Leonard S, Weyer P, Rhoads A, Siega-Riz AM, Renée Anthony T, Burns TL, Conway KM, Langlois PH, Romitti PA.
Birth Defects Res. 2018 Nov 15;110(19):1455-1467. doi: 10.1002/bdr2.1386. 

Natural Background and Anthropogenic Arsenic Enrichment in Florida Soils, Surface Water, and Groundwater: A Review with a Discussion on Public Health Risk.
Missimer TM, Teaf CM, Beeson WT, Maliva RG, Woolschlager J, Covert DJ.
Int J Environ Res Public Health. 2018 Oct 17;15(10). pii: E2278. doi: 10.3390/ijerph15102278. Review.

Hydrogeochemical evidences for targeting sources of safe groundwater supply in arsenic-affected multi-level aquifer systems.
Du Y, Deng Y, Ma T, Lu Z, Shen S, Gan Y, Wang Y.
Sci Total Environ. 2018 Dec 15;645:1159-1171. doi: 10.1016/j.scitotenv.2018.07.173.

Low-level exposure to arsenic in drinking water and incidence rate of stroke: A cohort study in Denmark.
Ersbøll AK, Monrad M, Sørensen M, Baastrup R, Hansen B, Bach FW, Tjønneland A, Overvad K, Raaschou-Nielsen O.
Environ Int. 2018 Nov;120:72-80. doi: 10.1016/j.envint.2018.07.040. 

Arsenic reduction

Arsenic Exposure and Cancer Risk Reduction with Local Ordinance Requiring Whole-House Dual-Tank Water Treatment Systems.
Rockafellow-Baldoni M, Spayd SE, Hong JY, Meng Q, Ohman-Strickland P, Robson MG.
Hum Ecol Risk Assess. 2018;24(5):1256-1267. doi: 10.1080/10807039.2017.1411779.

Arsenic removal

Addressing technical barriers for reliable, safe removal of fluoride from drinking water using minimally processed bauxite ores.
Buckley HL, Molla NJ, Cherukumilli K, Boden KS, Gadgil AJ.
Dev Eng. 2018;3:175-187. doi: 10.1016/j.deveng.2018.06.002.

Ultrafast removal of arsenic using solid solution of aero-gel based Ce1-XTixO2-Y oxide nanoparticles.
Mishra PK, Rai PK.
Chemosphere. 2019 Feb;217:483-495. doi: 10.1016/j.chemosphere.2018.11.003.

3-Mercapto-propanoic acid modified cellulose filter paper for quick removal of arsenate from drinking water.
Pramanik K, Sarkar P, Bhattacharyay D.
Int J Biol Macromol. 2019 Feb 1;122:185-194. doi: 10.1016/j.ijbiomac.2018.10.065. 

Arsenic is an element found in nature, in minerals, in rocks and which can enter the air, water and soil.

The presence of arsenic in mineral waters has been regulated, over the years, by many legislative provisions.

Arsenic is considered a human carcinogen and a natural contaminant of groundwater.

For this reason it was established that (1):

• water is not a commercial product like any other but, rather, a heritage which must be protected, defended and treated as such
• arsenic (and its compounds) it is one of the main water pollutants

In particular, as regards the natural mineral waters in its state at source, they may undergo treatments for the removal of arsenic by separation  with ozone-enriched air (2).

USA. The federal limit for arsenic in bottled water is 10 parts per billion. The methods are those published in the latest edition of the American Public Health Association's "Standard methods for the examination of water and wastewater". However in the United States, up to 14% of the population depends on private wells as a primary source of drinking water. The US government does not regulate contaminants in private wells (5).

EUROPE. The maximum limit of the concentration of arsenic present in mineral waters, set by the European Community regulation, is 10 micrograms/liter (3). Exceeding this maximum limit may present a health risk.

The most recent studies

Epidemiological studies have shown that intake of drinking water with high levels of arsenic (>100μg/L) is associated with risk for cardiovascular diseases (5).

Based on the relevant epidemiological studies with individual-level data, a threshold level for inorganic arsenic in the drinking water for these cancers is estimated to be around 100µg/L, with strong evidence that it is between 50 and 150µg/L, consistent with the value calculated based on mechanistic, in vitro and in vivo investigations (6).

Older people between the ages of 75 and 80 have been particularly vulnerable to the risk of cancer caused by arsenic (7).

Other studies on arsenic for further information.

References______________________________________

(1) Directive 2000/60/EC of the European Parliament and of the Council of 23 October 2000 establishing a framework for Community action in the field of water policy Official Journal L 327 , 22/12/2000 P. 0001 - 0073
(2) Directive 2009/54/EC of the european parliamentand off the council of 18 June 2009 on the exploitation and marketing of natural mineral waters
(3) Council Directive 98/83/EC of 3 November 1998 on the quality of water intended for human consumption Official Journal L 330 , 05/12/1998 P. 0032 - 0054
(4) Low-level arsenic in drinking water and risk of incident myocardial infarction: A cohort study. Monrad M, Ersbøll AK, Sørensen M, Baastrup R, Hansen B, Gammelmark A, Tjønneland A, Overvad K, Raaschou-Nielsen O Environ Res. 2017 Apr;154:318-324. doi: 10.1016/j.envres.2017.01.028. Epub 2017 Jan 31.
(5) Dose-response for assessing the cancer risk of inorganic arsenic in drinking water: the scientific basis for use of a threshold approach. Tsuji JS, Chang ET, Gentry PR, Clewell HJ, Boffetta P, Cohen SM. Crit Rev Toxicol. 2019 Apr 1:1-49. doi: 10.1080/10408444.2019.1573804.
(7) Estimating and comparing the cancer risks from THMs and low-level arsenic in drinking water based on disability-adjusted life years.  Zhang H, Chang S, Wang L, Wang W.  Water Res. 2018 Nov 15;145:83-93. doi: 10.1016/j.watres.2018.08.012. 

Titanium dioxide (TiO₂) is a chemical compound, a white pigment that creates a white or opaque color.

It is now present in many applications: cosmetics, paints, papers, sunscreens, pharmaceutical additives.

We frequently find it in the coatings of medicinal tablets, beverages, in sunscreens as anti-UV filter.

Widely used as an additive in the food industry as a bleaching agent (E171).

Titanium dioxide has so far been considered safe and inert.

A brief history on the evolution of scientific studies on the safety of this chemical component.

 2011 - 2016

Titanium dioxide in our everyday life; is it safe? The answer is cautious : "we do not have reliable data on its absorption, distribution, excretion and toxicity on oral exposure." (1).

Some studies recognize a positive value in the biomedical applications of titanium dioxide (2).

Other studies do not reveal any toxicological problems (3).

In 2016, EFSA provides an opinion with a review of the safety of titanium dioxide (TiO₂, E171) when used as a food additive.
The present Opinion deals with the re‐evaluation of the safety of titanium dioxide (TiO₂, E 171) when used as a food additive. From the available data on absorption, distribution and excretion, the EFSA Panel on Food Additives and Nutrient Sources added to Food concluded that the absorption of orally administered TiO₂ is extremely low and the low bioavailability of TiO2 appears to be independent of particle size. The Panel concluded that the use of TiO2 as a food additive does not raise a genotoxic concern. From a carcinogenicity study with TiO₂ in mice and in rats, the Panel chose the lowest no observed adverse effects levels (NOAEL) which was 2,250 mg TiO₂/kg body weight (bw) per day for males from the rat study, the highest dose tested in this species and sex. The Panel noted that possible adverse effects in the reproductive system were identified in some studies conducted with material which was either non‐food‐grade or inadequately characterised nanomaterial (i.e. not E 171). There were no such indications in the available, albeit limited, database on reproductive endpoints for the food additive (E 171). The Panel was unable to reach a definitive conclusion on this endpoint due to the lack of an extended 90‐day study or a multigeneration or extended‐one generation reproduction toxicity study with the food additive (E 171). Therefore, the Panel did not establish an acceptable daily intake (ADI). The Panel considered that, on the database currently available and the considerations on the absorption of TiO₂, the margins of safety (MoS) calculated from the NOAEL of 2,250 mg TiO2/kg bw per day identified in the toxicological data available and exposure data obtained from the reported use/analytical levels of TiO₂ (E 171) would not be of concern. The Panel concluded that once definitive and reliable data on the reproductive toxicity of E 171 were available, the full dataset would enable the Panel to establish a health‐based guidance value (ADI) (4).

 2017 - 2019

Since 2017, some studies carried out using ultramodern nano techniques (European Synchrotron of Grenoble) attribute to genotoxide genotoxic characteristics.

If the Titanium Dioxide is inlaid into the skin, as in the case of tattoos,  additional laboratory-based mass spectrometric methods demonstrated simultaneous transport of organic pigments, heavy metals and titanium from skin to regional lymph nodes. The toxicity of TiO₂depends on its speciation (crystal structure) which can be either rutile or the more harmful photocatalytically active anatase. The contribution of tattoo inks to the overall body load on toxic elements, the speciation of TiO₂, and the identities and size ranges of pigment particles migrating from subepidermal skin layers towards lymph nodes have never been analytically investigated in humans before. The average particle size in tattoo inks may vary from 1 µm. Therefore most tattoo inks contain at least a small fraction of particles in the nano range (5).

The deposit of particles leads to chronic enlargement of the respective lymph node and lifelong exposure. With the detection of the same organic pigments and inorganic TiO₂ in skin and lymph nodes, we provide strong analytical evidence for the migration of pigments from the skin towards regional lymph nodes in humans. So far, this only has been assumed to occur based on limited data from mice and visual observations in humans (6).

This study by 19 researchers at the University of Toulon notes with concern that the daily intake of TiO2 nanoparticles, as they overcome the normal defenses of the human body, is associated with an increased risk of chronic intestinal inflammation and carcinogenesis (7).

This 2018 study confirms the relationship between titanium dioxide nanoparticles and the EMT process in colorectal cancer cells (8).

In 2019 this study suggests that ocean acidification would enhance the accumulation of titanium dioxide nanoparticles in edible bivalves and may therefore increase the health risk for seafood consumers (9).

2019 - The French law prohibits the use of titanium dioxide (LOI n° 2018-938 du 30 octobre 2018) in the food sector.

11-6-2020 I wrote to the European Directorate for Health and Food Safety (DG SANTE) reiterating doubts about the safety of parabens and E171 titanium dioxide. Finally, also from this body came the answer that clarifies all doubts:

"Regarding the use of methyl- and propylparaben as excipients in oral medicinal products for human use, I would advise you to look at the information provided by the European Medicines Agency at https://www.ema.europa.eu/en/use-methyl-propylparaben-excipients-human-medicinal-products-oral-use This discussion paper deals with methyl- and propylparaben, as these are the parabens predominantly used in oral pharmaceutical formulations. The focus of this paper is on possible endocrine disrupting effects in humans.

Regarding titanium dioxide, the European Food Safety Authority published its opinion on May 6, 2021 and concluded that, based on all available evidence, a concern for genotoxicity cannot be ruled out, and given the many uncertainties, E 171 can no longer be considered safe when used as a food additive. As mentioned in a tweet on the same day, following EFSA's new scientific opinion on the food additive E171, we will propose to ban its use in the EU. https://twitter.com/food_eu/status/1390347410476523521

Regarding medicinal products, the Commission has asked the European Medicines Agency to assess the effect on the use of TiO2 in medicinal products and the feasibility of alternatives to replace TiO2, if possible, without impact on the quality, safety and efficacy of medicinal products. A decision will be made by the Commission based on the analysis provided by the Agency."

Now, how long will it be before these ingredients are permanently removed from our medicines?

 Bibliografia_____________________

(1) Skocaj M, Filipic M, Petkovic J, Novak S. Titanium dioxide in our everyday life; is it safe? Radiol Oncol. 2011 Dec;45(4):227-47. doi: 10.2478/v10019-011-0037-0.

(2) Fei Yin Z, Wu L, Gui Yang H, Hua Su Y. Recent progress in biomedical applications of titanium dioxide. Phys Chem Chem Phys. 2013 Feb 28. 

(3) Naya M, Kobayashi N, Ema M, Kasamoto S, Fukumuro M, Takami S, Nakajima M, Hayashi M, Nakanishi J. In vivo genotoxicity study of titanium dioxide nanoparticles using comet assay following intratracheal instillation in rats. Regul Toxicol Pharmacol. 2012 Feb;62(1):1-6. doi: 10.1016/j.yrtph.2011.12.002.

(4) Re-evaluation of titanium dioxide (E 171) as a food additive. EFSA Journal 2016;14(9):4545 [83 pp.].

(5) Ines Schreiver, Bernhard Hesse, Christian Seim, Hiram Castillo-Michel, Julie Villanova, Peter Laux, Nadine Dreiack, Randolf Penning, Remi Tucoulou, Marine Cotte & Andreas Luch Synchrotron-based ν-XRF mapping and μ-FTIR microscopy enable to look into the fate and effects of tattoo pigments in human skin Scientific Reports 7, Article number: 11395 (2017) https://doi.org/10.1038/s41598-017-11721-z

(6)  Lehner K, Santarelli F, Vasold R, Penning R, Sidoroff A, König B, Landthaler M, Bäumler W. Black tattoos entail substantial uptake of genotoxicpolycyclic aromatic hydrocarbons (PAH) in human skin and regional lymph nodes. PLoS One. 2014 Mar 26;9(3):e92787. doi: 10.1371/journal.pone.0092787. eCollection 2014.

(7) Sarah Bettini, Elisa Boutet-Robinet, Christel Cartier, Christine Coméra, Eric Gaultier, Jacques Dupuy, Nathalie Naud, Sylviane Taché, Patrick Grysan, Solenn Reguer, Nathalie Thieriet, Matthieu Réfrégiers, Dominique Thiaudière, Jean-Pierre Cravedi, Marie Carrière, Jean-Nicolas Audinot, Fabrice H. Pierre, Laurence Guzylack-Piriou and Eric Houdeau Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon  Sci Rep. 2017; 7: 40373. Published online 2017 Jan 20. doi: 10.1038/srep40373

(8) Setyawati MI, Sevencan C, Bay BH, Xie J, Zhang Y, Demokritou P, Leong DT. Nano-TiO2 Drives Epithelial-Mesenchymal Transition in Intestinal Epithelial Cancer Cells. Small. 2018 Jul 2:e1800922. doi: 10.1002/smll.201800922.

(9) Shi W, Han Y, Guo C, Su W, Zhao X, Zha S, Wang Y, Liu G.  Ocean acidification increases the accumulation of titanium dioxide nanoparticles (nTiO2) in edible bivalve mollusks and poses a potential threat to seafood safety.  Sci Rep. 2019 Mar 5;9(1):3516. doi: 10.1038/s41598-019-40047-1.

Palm oil is a much-discussed oil, used in the food industry both for its low cost and its pleasant taste, and here are some studies of 2015-2016.

In September 2015, a group of researchers (1) engaged in lengthy research showed that the association between palm oil intake and cancer might be controversial due to some important factors such as:

• population heterogeneity
• difficulty to consider other risk factors
• other pathological conditions

 However, it reiterated recently, that a growing number of tests have highlighted the negative effects of excess palmitic acid on mitochondrial function mediated by oxidative stress, an effect otherwise known as lipotoxicity. Whereas, with regard to cardiovascular risk, bearing in mind the previous important factors, contrasting results have been reported, above all because the tests were carried out on subjects with normal cholesterol values ​​who had taken normal doses of polyunsaturated fatty acids.

Another 2015 study reiterated the high saturated fat content and provided discouraging results on the increase in harmful LDL cholesterol (2).

Comparing palm oil and sunflower oil, palm oil was confirmed as a highly saturated vegetable oil, which can induce dysfunctions of the lipid metabolism of the liver before touching the serum lipid levels. On the other hand, sunflower oil, a highly unsaturated vegetable oil, has been shown to be well metabolised in the liver (3).

All these studies agreed in attributing to palm oil a high content of saturated fats and, in a long and articulated examination of the biological and nutritional properties of the oil, carried out by a group of researchers of the University of Naples, controversial results were produced. We can see in Figure 3, which is of particular interest, the areas involved in the human body (4).

A study aimed at detecting mutations produced in palm oil, used for frying potato chips, found that thermo-oxidative changes took place in the composition of fatty acids and alterations in the colour were produced at temperatures of 150°, 165° and 180°. Therefore, the more the temperature increases, the more the oxidation of palm oil increases (5).

It has a relatively high content of saturated fats of about 50%, of which palmitic acid represents 45% (6).

References______________________________________

(1) Biological and Nutritional Properties of Palm Oil and Palmitic Acid: Effects on Health.
Mancini A, Imperlini E, Nigro E, Montagnese C, Daniele A, Orrù S, Buono P.
Molecules. 2015 Sep 18;20(9):17339-61. doi: 10.3390/molecules200917339. Review.  

(2) Palm Oil Consumption Increases LDL Cholesterol Compared with Vegetable Oils Low in Saturated Fat in a Meta-Analysis of Clinical Trials.
Sun Y, Neelakantan N, Wu Y, Lote-Oke R, Pan A, van Dam RM.
J Nutr. 2015 Jul;145(7):1549-58. doi: 10.3945/jn.115.210575. 

 (3) Effects of palm and sunflower oils on serum cholesterol and fatty liver in rats.
Go RE, Hwang KA, Kim YS, Kim SH, Nam KH, Choi KC.
J Med Food. 2015 Mar;18(3):363-9. doi: 10.1089/jmf.2014.3163. 

(4) Biological and Nutritional Properties of Palm Oil and Palmitic Acid: Effects on Molecules. 2015 Sep 18;20(9):17339-61. doi: 10.3390/molecules200917339.

(5) The effect of frying on glycidyl esters content in palm oil.   - Aniołowska M, Kita A. Food Chem. 2016 Jul 15;203:95-103. doi: 10.1016/j.foodchem.2016.02.028. 

(6) The effect of pan frying on thermooxidative stability of refined rapeseed oil and professional blend
Magda Aniołowska, Hamdy Zahran, Agnieszka Kita
J Food Sci Technol. 2016 Jan; 53(1): 712–720. Published online 2015 Sep 16. doi: 10.1007/s13197-015-2020-z