Oral two-generation reproduction toxicity study with NM-200 synthetic amorphous silica in Wistar rats

Wolterbeek, André; Oosterwijk, Thies; Schneider, Steffen; Landsiedel, Robert; Groot, Didima de; Ee, Renz van; Wouters, Mariëlle; Sandt, Han van de

doi:10.1016/j.reprotox.2015.03.006

Cited by 28 publications

(18 citation statements)

References 8 publications

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“…Buesen et al [ 92 ] did not record any treatment-related adverse effects of 15 nm SiO 2 (without or with different surface functionalizations) in rats upon 28-day oral administration (OECD TG 407). Hofmann et al [ 93 ] and Wolterbeek et al [ 94 ] observed no reproductive or developmental toxicity of precipitated SiO 2 in rats (OECD TG 414 and 416, respectively); and Kolle et al [ 95 ] reported no in vitro eye-irritating potential of either precipitated or pyrogenic SiO 2 in the bovine corneal opacity and permeability assay (OECD TG 437) or the reconstructed human cornea–like epithelium test method (OECD TG 492).…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Short-Term Pulmonary Toxicity of Differently Sized Colloidal Amorphous SiO2

Wiemann¹,

Sauer²,

Vennemann³

et al. 2018

Nanomaterials

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In vitro prediction of inflammatory lung effects of well-dispersed nanomaterials is challenging. Here, the in vitro effects of four colloidal amorphous SiO2 nanomaterials that differed only by their primary particle size (9, 15, 30, and 55 nm) were analyzed using the rat NR8383 alveolar macrophage (AM) assay. Data were compared to effects of single doses of 15 nm and 55 nm SiO2 intratracheally instilled in rat lungs. In vitro, all four elicited the release of concentration-dependent lactate dehydrogenase, β-glucuronidase, and tumor necrosis factor alpha, and the two smaller materials also released H2O2. All effects were size-dependent. Since the colloidal SiO2 remained well-dispersed in serum-free in vitro conditions, effective particle concentrations reaching the cells were estimated using different models. Evaluating the effective concentration–based in vitro effects using the Decision-making framework for the grouping and testing of nanomaterials, all four nanomaterials were assigned as “active.” This assignment and the size dependency of effects were consistent with the outcomes of intratracheal instillation studies and available short-term rat inhalation data for 15 nm SiO2. The study confirms the applicability of the NR8383 AM assay to assessing colloidal SiO2 but underlines the need to estimate and consider the effective concentration of such well-dispersed test materials.

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Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Short-Term Pulmonary Toxicity of Differently Sized Colloidal Amorphous SiO2

Wiemann¹,

Sauer²,

Vennemann³

et al. 2018

Nanomaterials

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“…Generally, nanomaterials are of low systemic availability upon oral exposure and do not elicit apical effects (Buesen et al 2014). Also, the few available oral reproductive toxicity studies do not point to effects on fertility or development of, e.g., SiO 2 NM-200 (Hofmann et al 2015; Wolterbeek et al 2015). Similarly, the available in vitro and in vivo studies do not report unintentional permeability or systemic availability of dermally applied nanomaterials, such as nanomaterials used in sunscreen lotions (Monteiro-Riviere et al 2011; Landsiedel et al 2012b).…”

Section: Nanomaterials Hazard Assessment Upon Oral Dermal or Local Ementioning

confidence: 99%

Safety assessment of nanomaterials using an advanced decision-making framework, the DF4nanoGrouping

et al. 2017

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As presented at the 2016 TechConnect World Innovation Conference on 22–25 May 2016 in Washington DC, USA, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) ‘Nano Task Force’ proposes a Decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping) consisting of three tiers to assign nanomaterials to four main groups with possible further subgrouping to refine specific information needs. The DF4nanoGrouping covers all relevant aspects of a nanomaterial’s life cycle and biological pathways: intrinsic material properties and system-dependent properties (that depend upon the nanomaterial’s respective surroundings), biopersistence, uptake and biodistribution, and cellular and apical toxic effects. Use, release, and exposure route may be applied as ‘qualifiers’ to determine if, e.g., nanomaterials cannot be released from products, which may justify waiving of testing. The four main groups encompass (1) soluble, (2) biopersistent high aspect ratio, (3) passive, and (4) active nanomaterials. The DF4nanoGrouping foresees a stepwise evaluation of nanomaterial properties and effects with increasing biological complexity. In case studies covering carbonaceous nanomaterials, metal oxide, and metal sulfate nanomaterials, amorphous silica and organic pigments (all nanomaterials having primary particle sizes below 100 nm), the usefulness of the DF4nanoGrouping for nanomaterial hazard assessment was confirmed. The DF4nanoGrouping facilitates grouping and targeted testing of nanomaterials. It ensures that sufficient data for the risk assessment of a nanomaterial are available, and it fosters the use of non-animal methods. No studies are performed that do not provide crucial data. Thereby, the DF4nanoGrouping serves to save both animals and resources.

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“…A GLP oral two-generation reproductive toxicity study was recently performed in the Wistar rat according to OECD guideline 416 (Wolterbeek et al 2015). The administration by gavage of precipitated synthetic amorphous silica (NM-200, purity 96.5 %) at doses up to 1000 mg/kg bw/day had no adverse effects on the reproductive performance of rats or on the growth and development of the offspring into adulthood for two consecutive generations.…”

Section: Reproductive and Developmental Toxicitymentioning

confidence: 99%

The safety of nanostructured synthetic amorphous silica (SAS) as a food additive (E 551)

Fruijtier-Pölloth¹

2016

Arch Toxicol

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Key messages Particle sizes of E 551 products are in the micrometre range. The typical external diameters of the constituent particles (aggregates) are greater than 100 nm. E 551 does not break down under acidic conditions such as in the stomach, but may release dissolved silica in environments with higher pH such as the intestinal tract. E 551 is one of the toxicologically most intensively studied substances and has not shown any relevant systemic or local toxicity after oral exposure. AbstractSynthetic amorphous silica (SAS) meeting the specifications for use as a food additive (E 551) is and has always been produced by the same two production methods: the thermal and the wet processes, resulting in E 551 products consisting of particles typically in the micrometre size range. The constituent particles (aggregates) are typically larger than 100 nm and do not contain discernible primary particles. Particle sizes above 100 nm are necessary for E 551 to fulfil its technical function as spacer between food particles, thus avoiding the caking of food particles. Based on an in-depth review of the available toxicological information and intake data, it is concluded that the SAS products specified for use as food additive E 551 do not cause adverse effects in oral repeated-dose studies including doses that exceed current OECD guideline recommendations. In particular, there is no evidence for liver toxicity after oral intake. No adverse effects have been found in oral fertility and developmental toxicity studies, nor are there any indications from in vivo studies for an immunotoxic or neurotoxic effect. SAS is neither mutagenic nor genotoxic in vivo. In intact cells, a direct interaction of unlabelled and unmodified SAS with DNA was never found. Differences in the magnitude of biological responses between pyrogenic and precipitated silica described in some in vitro studies with murine macrophages at exaggerated exposure levels seem to be related to interactions with cell culture proteins and cell membranes. The in vivo studies do not indicate that there is a toxicologically relevant difference between SAS products after oral exposure. It is noted that any silicon dioxide product not meeting established specifications, and/or produced to provide new functionality in food, requires its own specific safety and risk assessment.

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Oral two-generation reproduction toxicity study with NM-200 synthetic amorphous silica in Wistar rats

Cited by 28 publications

References 8 publications

In Vitro and In Vivo Short-Term Pulmonary Toxicity of Differently Sized Colloidal Amorphous SiO2

In Vitro and In Vivo Short-Term Pulmonary Toxicity of Differently Sized Colloidal Amorphous SiO2

Safety assessment of nanomaterials using an advanced decision-making framework, the DF4nanoGrouping

The safety of nanostructured synthetic amorphous silica (SAS) as a food additive (E 551)

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