Re‐evaluation of calcium silicate (E 552), magnesium silicate (E 553a(i)), magnesium trisilicate (E 553a(ii)) and talc (E 553b) as food additives

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re‐evaluating the safety of calcium silicate (E 552), magnesium silicate (E 553a) and talc (E 553b) when used as food additives. In 1991, the Scientific Committee on Food (SCF) established a group acceptable daily intake (ADI) ‘not specified’ for silicon dioxide and silicates. The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) recently provided a scientific opinion re‐evaluating the safety of silicon dioxide (E 551) when used as a food additive. The Panel noted that the absorption of silicates and talc was very low; there was no indication for genotoxicity or developmental toxicity for calcium and magnesium silicate and talc; and no confirmed cases of kidney effects have been found in the EudraVigilance database despite the wide and long‐term use of high doses of magnesium trisilicate up to 4 g/person per day over decades. However, the Panel considered that accumulation of silicon from calcium silicate in the kidney and liver was reported in rats, and reliable data on subchronic and chronic toxicity, carcinogenicity and reproductive toxicity of silicates and talc were lacking. Therefore, the Panel concluded that the safety of calcium silicate (E 552), magnesium silicate (E 553a(i)), magnesium trisilicate (E 553a(ii)) and talc (E 553b) when used as food additives cannot be assessed. The Panel considered that there is no mechanistic rationale for a group ADI for silicates and silicon dioxide and the group ADI established by the SCF is obsolete. Based on the food supplement scenario considered as the most representative for risk characterisation, exposure to silicates (E 552–553) for all population groups was below the maximum daily dose of magnesium trisilicate used as an antacid (4 g/person per day). The Panel noted that there were a number of approaches, which could decrease the uncertainties in the current toxicological database. These approaches include – but are not limited to – toxicological studies as recommended for a Tier 1 approach as described in the EFSA Guidance for the submission of food additives and conducted with an adequately characterised material. Some recommendations for the revision of the EU specifications were proposed by the Panel

In vitro response of rat pleural mesothelial cells to talc samples in genotoxicity assays (sister chromatid exchanges and DNA repair)

International audienceThe genotoxicity of three samples of talc has been determined using in vitro cell systems previously developed for testing asbestos fibres. The talc samples used consisted of particles of respirable size in order to test the effect of particles likely to be deposited in the lung. Genotoxicity was tested in cultures of rat pleural mesothelial cells (RPMC) using genotoxicity assays for unscheduled DNA synthesis (UDS) and sister chromatid exchanges (SCEs). The effects were compared with those obtained with negative controls (attapulgite and anatase) and positive controls (chrysotile and crocidolite asbestos). In contrast to asbestos, none of the talc samples, nor the negative controls, induced enhancement of UDS or SCEs in treated cultures in comparison with the untreated cultures

Accumulation of platelets in the lung and liver and their degranulation following antigen-challenge in sensitized mice

1. Mast cells and basophils are believed to trigger allergic reactions and anaphylaxis. They rapidly release histamine (H), a typical mediator of inflammation, in response to antigens. In the mouse, platelets contain much 5-hydroxytryptamine (5HT), an additional inflammatory mediator, while human platelets contain both H and 5HT. Here, we examined the response of platelets in sensitized mice to antigen challenge. 2. Platelets accumulated in the lung and liver almost immediately after intravenous injection of ovalbumin (OVA), in mice sensitized to it, and platelet degranulation occurred during these reactions. 3. These responses of platelets preceded H release from mast cells and/or basophils, occurred at doses of OVA lower than those inducing H release, and contributed to the signs of shock. 4. We reported previously that intravenous injection into mice of LPS (a membrane constituent of gram-negative bacteria) induces a similar platelet response (accumulation of platelets in the lung and liver) and shock. 5. Blood that has passed through the body (other than the digestive tract) passes first to the lungs before being recirculated by the heart, and blood that has passed through the digestive tract passes next to the liver. Thus, our findings suggest that in addition to their role in haemostasis, platelets, tiny anuclear cytoplasts, may be important in both innate and acquired immunity, and that the lung and liver may be the fronts at which platelets wage war on pathogens

Genome-wide analysis of target genes regulated by HoxB4 in hematopoietic stem and progenitor cells developing from embryonic stem cells

Forced expression of the transcription factor HoxB4 has been shown to enhance the self-renewal capacity of mouse bone marrow hematopoietic stem cells (HSCs) and confer a long-term repopulating capacity to yolk sac and embryonic stem (ES) cell–derived hematopoietic precursors. The fact that ES cell–derived precursors do not repopulate bone marrow without HoxB4 underscores an important role for HoxB4 in the maturation of ES-derived hematopoietic precursors into long-term repopulating HSCs. However, the precise molecular mechanism underlying this process is barely understood. In this study, we performed a genome-wide analysis of HoxB4 using ES cell–derived hematopoietic stem/progenitor cells. The results revealed many of the genes essential for HSC development to be direct targets of HoxB4, such as Runx1, Scl/Tal1, Gata2, and Gfi1. The expression profiling also showed that HoxB4 indirectly affects the expression of several important genes, such as Lmo2, Erg, Meis1, Pbx1, Nov, AhR, and Hemgn. HoxB4 tended to activate the transcription, but the down-regulation of a significant portion of direct targets suggested its function to be context-dependent. These findings indicate that HoxB4 reprograms a set of key regulator genes to facilitate the maturation of developing HSCs into repopulating cells. Our list of HoxB4 targets also provides novel candidate regulators for HSCs