Toxicological Hazard Research Articles

Chocolate toxicosis in pets

Chocolate ingestion is very common in pets, particularly dogs, but has also been reported in other animals including cats and rabbits. Most cases occur around Christmas and Easter, when large amounts of chocolate are often present in the home in the form of chocolate bars, snacks, confectionery, Easter eggs and chocolate figurines. Chocolate-covered raisins, nuts and coffee beans present an additional toxicological hazard in dogs. The type of chocolate is defined in law by the percentage of cocoa solids, with dark (plain) chocolate containing more than milk chocolate. The main toxic component of chocolate is theobromine, a methylxanthine, although caffeine, another methylxanthine, is also present. These cause central nervous system stimulation with cardiac and respiratory hyperactivity. Signs include gastrointestinal effects, excitability, hyperactivity, tachycardia, tremors, hypertension and hyperthermia. Signs of toxicosis generally occur within a few hours of ingestion. The mainstays of treatment are decontamination and supportive care with rehydration, control of central nervous system stimulation and arrhythmias as required. Most pets recover fully, and death is uncommon; however, prognosis is more guarded in pets with seizures or arrhythmias.

Protective role of hesperetin in Drosophila melanogaster model of ferrous sulphate-induced toxicity

The toxicological hazard of iron-containing products is a public health concern that inspires research in identifying and developing readily available, inexpensive antidotes. Natural products, like plant-sourced antioxidants, can be of great value in this regard. Hesperetin a flavonoid abundantly present in citrus fruits is known to possess a diverse pharmacological and antioxidant attribute. The present study investigated the alleviation of detrimental effects of ferrous sulphate (FeSO4) by hesperetin in Drosophila melanogaster. Flies were exposed to FeSO4 (10 µM) alone or supplemented with hesperetin (50 or 100 µM) via diet for 7 consecutive days. Antioxidant enzyme activities, non-enzymatic antioxidant levels, acetylcholinesterase activity and oxidative stress markers were then measured. Hesperetin supplementation significantly (p < 0.05) attenuated FeSO4-induced oxidative stress by enhancement of enzymic antioxidants (catalase and glutathione-S-transferases) activities, preservation of non-enzymic antioxidants (total thiols and non-protein thiols), and reduction of other markers of oxidative stress (hydrogen peroxide, protein carbonyl and lipid peroxidation) in D. melanogaster. In addition, hesperetin supplementation decreased nitric oxide levels and enhanced acetylcholinesterase activity. Furthermore, hesperetin supplementation improved FeSO4-induced locomotor deficit, while there was no significant difference in cell viability (mitochondrial metabolic rate) in the treatment groups. This study suggests that hesperetin might be a promising functional agent in preventing iron toxicity and similar metal-induced impairments.

Progress in toxicogenomics to protect human health.

Toxicogenomics measures molecular features, such as transcripts, proteins, metabolites and epigenomic modifications, to understand and predict the toxicological effects of environmental and pharmaceutical exposures. Transcriptomics has become an integral tool in contemporary toxicology research owing to innovations in gene expression profiling that can provide mechanistic and quantitative information at scale. These data can be used to predict toxicological hazards through the use of transcriptomic biomarkers, network inference analyses, pattern-matching approaches and artificial intelligence. Furthermore, emerging approaches, such as high-throughput dose-response modelling, can leverage toxicogenomic data for human health protection even in the absence of predicting specific hazards. Finally, single-cell transcriptomics and multi-omics provide detailed insights into toxicological mechanisms. Here, we review the progress since the inception of toxicogenomics in applying transcriptomics towards toxicology testing and highlight advances that are transforming risk assessment.

Comprehensive review of toxicological risks in wild game consumption

The consumption of wild game meat, rooted in cultural traditions and increasingly favored as a natural food source, presents both nutritional benefits and toxicological challenges. While wild game offers a rich source of protein and essential nutrients, it also carries unique risks associated with environmental contaminants, naturally occurring toxins, and zoonotic diseases. This review provides a comprehensive analysis of these toxicological hazards, drawing from a wide range of scientific literature. It examines the origins of toxins in wild game, including heavy metals, pesticides, and other environmental pollutants, as well as the risks posed by animals' natural diets and traditional hunting methods. Additionally, the review addresses the public health implications of consuming contaminated wild game and offers strategies for mitigating these risks. By exploring the complex interplay between wild game consumption and toxicology, this review aims to inform both consumers and public health professionals, emphasizing the importance of safe practices in the handling and preparation of wild game meat to minimize potential health hazards.

Thermal degradation of capsaicin and dihydrocapsaicin: Mechanism and hazards of volatile products

Food safety issues have become unprecedentedly notable. To ensure the safe use of capsaicin (CAP) and dihydrocapsaicin (DHCAP) in the food sector, their thermal degradation characteristics was examined for the first time through thermogravimetric analysis (TGA) and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) analysis. The second major phase occurred within the temperature range of 265–425 ℃, leading to substantial weight reductions of 96.13 % for CAP and 92.76 % for DHCAP. Thermodynamic parameters, calculated using the Flynn–Wall–Ozawa (FWO), Kissinger–Akahira–Sunose (KAS), and Coats–Redfern (C–R) methods, indicated that the thermal decomposition of both CAP and DHCAP was non-spontaneous and followed an F1 mechanism (−ln(1−α)). The pyrolysis of CAP and DHCAP released several volatile compounds, including CAP, DHCAP, Z-9-octadecenamide, octadecanamide, 9-decenenitrile, nonanenitrile, and 8-methylnonanoic acid. These compounds may pose certain toxicological risks and potential hazards to human health. The pyrolytic pathways for CAP and DHCAP are likely to involve the cleavage of alkyl C-N and/or amide bonds, as well as processes of deamidation and demethylation. Therefore, it is prudent to avoid heating food containing CAP and DHCAP above 265 ℃ during culinary preparation.

Assessment of performance of the profilers provided in the OECD QSAR toolbox for category formation of chemicals

Growing restrictions and bans on animal testing for chemical safety assessment under different regulations have led to an increasing use of alternative methods. Read-across is one of the major approaches used for this purpose, which relies on the identification of toxicological hazards of a data-poor or untested (target) chemical from data on other already-tested (source) similar chemicals. This requires the target substance to be first assigned to a group or category of ‘similar’ chemicals. The ‘similarity’ may be in terms of structural features alone, or in combination with certain rules that are based on mechanistic and/or toxicological aspects. In this regard, the OECD QSAR toolbox—a major free-access in silico platform—is widely used to derive toxicity predictions for a range of (eco) toxicological endpoints. The Toolbox allows the user to identify a set of similar chemicals (analogues) by computational ‘profilers’ that incorporate different structural alerts, or a combination of structural alerts and physicochemical and/or toxicokinetic rules relevant to a specific toxicological endpoint. The overall aim of this study was to assess the performance of the in silico profilers provided in the OECD QSAR Toolbox for reliability for identifying chemical analogues for category formation in a number of high-quality databases on mutagenicity, carcinogenicity, and skin sensitisation. The study also aimed to identify the reasons for any limitations in the performance of the profilers, and propose ways to improve their overall accuracy. The results showed that whilst some structural alerts are fit-for-purpose as such within the acceptable limits, others need refinement or a consideration for their possible exclusion from the profiler. Such refinements are imperative for a reliable use of the profilers in read-across and grouping/categorisation for classification, labelling and risk assessment of chemicals.

Hyaluronic acid impacts hematological endpoints and spleen histological features in African catfish (Clarias gariepinus)

Since its identification in the vitreous humour of the eye and laboratory biosynthesis, hyaluronic acid (HA) has been a vital component in several pharmaceutical, nutritional, medicinal, and cosmetic uses. However, little is known about its potential toxicological impacts on aquatic inhabitants. Herein, we investigated the hematological response of Clarias gariepinus to nominal doses of HA. To achieve this objective, 72 adult fish were randomly and evenly distributed into four groups: control, low-dose (0.5 mg/l HA), medium-dose (10 mg/l HA), and high-dose (100 mg/l HA) groups for two weeks each during both the exposure and recovery periods. The findings confirmed presence of anemia, neutrophilia, leucopoenia, lymphopenia, and eosinophilia at the end of exposure to HA. In addition, poikilocytosis and a variety of cytomorphological disturbances were observed. Dose-dependent histological alterations in spleen morphology were observed in the exposed groups. After HA removal from the aquarium for 2 weeks, the groups exposed to the two highest doses still exhibited a notable decline in red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin concentration, and an increase in mean corpuscular volume. Additionally, there was a significant rise in neutrophils, eosinophils, cell alterations, and nuclear abnormalities percentages, along with a decrease in monocytes, coupled with a dose-dependent decrease in lymphocytes. Furthermore, only the highest dose of HA in the recovered groups continued to cause a significant increase in white blood cells. White blood cells remained lower, and the proportion of apoptotic RBCs remained higher in the high-dose group. The persistence of most of the haematological and histological disorders even after recovery period indicates a failure of physiological compensatory mechanisms to overcome the HA-associated problems or insufficient duration of recovery. Thus, these findings encourage the inclusion of this new hazardous agent in the biomonitoring program and provide a specific pattern of hematological profile in HA-challenged fish. Further experiments are highly warranted to explore other toxicological hazards of HA using dose/time window protocols.

Phytochemistry and Biological Activities of Agrostemma Genus-A Review.

The family Caryophyllaceae comprises more than 2600 species spread widely across all the continents. Their economic importance is mainly as ornamentals (carnation) and as weeds in agriculture. Some species have been used traditionally (and some are still) in herbal medicine or as emulsifiers in food processing. These applications are based on the high content of triterpenoid saponins. Typical for this family are also ribosome-inactivating proteins (RIPs), which are potentially highly toxic. Agrostemma githago L. (common corncockle) was historically considered a serious toxicological hazard owing to cereal grain contamination by its seeds. Notwithstanding, it was also recommended as a drug by various herbalists. In this review, the literature was searched in the PubMed, Google Scholar, and Scopus databases for papers focused on the chemical composition and bioactivity of the two accepted species of the Agrostemma genus. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and MetaAnalysis (PRISMA) guidelines. Current research reports the cytotoxicity against neoplastic cells; the protection against oxidative stress; the suppression of Leishmania major culture growth; the inhibition of protein synthesis; and the antiviral, anti-angiogenic, and antihypercholesterolemic activities of common corncockle. The future prospects of using A. githago saponins as adjuvants in drug formulations and enhancing the cytotoxicity of RIPs are also discussed.

Carry-over rate of per- and polyfluoroalkyl substances to raw milk and human exposure risks in different regions of China

The widespread presence of per- and polyfluoroalkyl substances (PFAS) in various environmental matrices and their adverse health effects have gained worldwide attention. Therefore, numerous studies have focused on human exposure to PFAS through different pathways, such as fish and drinking water, and little attention has been paid to milk consumption. This study aimed to explore the transfer of PFAS by investigating the occurrence of PFAS in cow feed, drinking water, and raw milk from 20 regions of China and to assess the risk of human exposure to PFAS from raw milk. In total, 13, 15, and 7 PFAS were detected in cow feed, drinking water, and raw milk with total concentrations (∑PFAS) of 5.59 ± 2.91 ng/g (mean ± standard deviation), 11.91 ± 23.12 ng/L, and 0.15 ± 0.13 ng/mL, respectively. Perfluoropentanoic acid (PFPeA) was dominant with a concentration of 2.28 ± 1.75 ng/g, approximately 40.7 % of ∑PFAS in feed. Perfluorooctanoic acid (PFOA) and perfluorobutanoic acid (PFBA) were the dominant compounds found in drinking water at 4.80 ± 14.37 and 3.01 ± 6.06 ng/L, respectively. Additionally, PFOA (0.08 ± 0.09 ng/mL) was the most significant compound in raw milk, contributing 51.5 % of ∑PFAS. Moreover, the results of the carry-over rate (COR) were as follows: perfluorooctanesulfonic acid (PFOS, 29.58 %) > PFOA (15.78 %) > perfluorobutanesulfonic acid (PFBS, 9.45 %). According to the reference dose (RfD) established by the European Food Safety Authority (EFSA) in 2018, there is a potential toxicological hazard of PFOA exposure for preschool children through milk consumption. Notably, the health risk from PFOS for 1-year-old children in Central China exceeded that observed for humans in other regions and age groups. Our results showed that PFOS and PFOA were more likely to accumulate in cows and to be constantly transferred to milk, thus increasing the human health risk, especially in children.

Identification and Overcome the Harmful Situations Related to Chemical with the Help of Hazard Identification and Risk Assessment Using Failure Mode and Effective Analysis (FMEA) Method

Exposure of Chemical are a major occupational health and safety issue in chemical work place industry. Management of chemical hazards requires the combined efforts of occupational health and safety specialists, including generalist OHS professionals, occupational hygienists, and occupational health practitioners. This Research is about analysis of Hazards and their developed Control Measures in industrial chemicals, the manner in which their toxicity is assessed and the use of such assessments in regulatory decision-making. It begins with general points concerning toxicological data availability and hazard identification, then moves on to risk assessment and occupational exposure limits, and finally looks briefly at some standard specific toxicological issues, where the science is far from resolved after brief consideration of the historical context of chemical reactivity and toxicity issues, acute and chronic exposure, chemical hazard classification systems, and the identification, risk assessment, and control of chemical hazards

Chemical health hazards and toxicity of environmental pollutants on humans, animals and others: An overview

Toxicology, rooted in ancient civilizations and evolving through pivotal historical figures like Paracelsus and Alice Hamilton, has become a multidisciplinary field encompassing various branches such as pharmacology, medical, forensic, and environmental toxicology. This exploration embarks on a journey through time and science, unravelling the intricate interplay between chemicals, pollutants, and their profound impacts on human, animal, and environmental well-being. Spanning from ancient practices like the use of hemlock in Greek capital punishment to modern-day concerns surrounding industrial chemicals and pesticides, the review delves into the mechanisms by which toxins disrupt biochemical pathways and induce organ dysfunctions. From heavy metals and pesticides persistent effects on the nervous and reproductive systems to the carcinogenic properties of polychlorinated biphenyls (PCBs), hydrocarbons, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). The review highlights the diverse range of toxicants and their widespread impact on human health. Additionally, the review underscores the importance of proactive measures to mitigate exposure to harmful substances, advocating for the development of antidotes, bioremediation techniques, and stricter environmental regulations. By addressing the urgent need for comprehensive strategies to combat toxicological hazards, this review aims to contribute to ongoing efforts to safeguard public health and environmental sustainability in the face of evolving chemical threats.

Dog and cat exposures to drugs of abuse identified by the California animal health and food safety laboratory system 2013-2023.

While known animal exposures to human "drugs of abuse" (DA) were previously considered relatively uncommon in veterinary medicine, the trends are changing. Marijuana and amphetamines are among the 20 toxicants most frequently consulted about with the Pet Poison Helpline. When such exposures occur, they are typically considered emergencies. This retrospective study describes confirmed cases of DA exposure in pets from the California Animal Health and Food Safety Laboratory System (CAHFS), 2013-2023. Fifty-seven samples tested positive for DA through liquid chromatography with tandem mass spectrometry analysis (qualitative method). In 75% (43/57) of the DA screen tests, the detected drugs included amphetamine-type stimulants and metabolites (methamphetamine, amphetamine, or both). In 47% (27/57) of cases, a combination of more than one drug group was found. Most cases were diagnosed from a urine specimen. In at least 32% (18/57) of cases, the samples were submitted due to suspicions of animal cruelty, and at least 41% (23/57) of the patients were deceased when the samples were submitted. More studies on the prevalence of illicit drugs in small animals, using confirmatory testing, are warranted to fully understand the significance of this emerging toxicological hazard in veterinary medicine.

Patterns and outcomes of acute toxicological cases before, during, and after COVID-19 lockdown in Sohag University hospitals, Egypt.

Toxicologists manage poisoning by preventing, detecting, and treating it, which requires continuous data collection and analysis of toxicological hazards. The study aims to report and compare the pattern and outcome of acute toxicological cases admitted to Sohag University Hospitals during the COVID-19 lockdown (2020-2021) with the year before (2019) and the year after (2022). This comparative study reviewed the sociodemographic and clinical data in the medical records. The study showed that Sohag University Hospitals received 670 toxicological cases between 2019 and 2022; 105 cases in 2019, 347 cases in 2020-2021, and 218 cases in 2022. Most of patients were below seven years with no sex differences. Accidental poisoning was the most frequent toxicity. The oral route was the most common in the three studied periods. During the lockdown, metal phosphide was the most frequent (19.0%), while therapeutic agents were the most reported after the lockdown (23.9%). The delay time showed a significant difference between the studied periods (p-value<0.001). In the three studied periods, complete recovery was achieved in more than 70% of cases; however, the mortality rate and the rate of complications during the lockdown period (10.4% and 9.5%, respectively) were almost twice those of the year before and the year after the pandemic with significant odds ratio of mortality during pandemic (OR) 0.07 CI 95% (0.02, 0.11). The pandemic had a bad impact on outcomes as showed the highest percentage of mortality compared to before and after COVID-19 periods.

Adherence to the national guidance on foods and drinks to limit or avoid during pregnancy in England: the PEAR Study.

The National Health Service (NHS) England website provides guidance on foods/drinks to avoid or limit during pregnancy because of microbiological, toxicological or teratogenic hazards. The aims were to determine adherence and whether demographic characteristics were associated with adherence. Cross-sectional study. Online survey of postpartum women resident in England during pregnancy. Recently, postpartum women resident in England during their pregnancy (n 598; median age 33 (IQR 30-36) years) completed an online questionnaire (April-November 2022). Questions included those on consumption of twenty-one food/drink items that the NHS advises pregnant women to avoid/limit. The study is part of the Pregnancy, the Environment And nutRition (PEAR) Study. Summary statistics were used to determine proportions adhering to the guidance. Adjusted logistic regression was used to model the associations of adherence with demographic characteristics. Adherence was generally high (>90 % for eight of ten food/drink items to be avoided). However, among pre-pregnancy consumers, several items were not completely avoided, for example, 81 % (128/158) for game meat/gamebirds, 37 % (176/478) for cured meats and 17 % (81/467) for soft cheeses. Greater educational attainment (e.g. caffeinated soft drinks OR 2·25 (95 % CI 1·28, 3·94)), greater maternal age (e.g. oily fish 1·64 (1·05, 2·56)) and lower parity (e.g. caffeinated coffee 0.28 (0.11, 0.69)) were the most usual characteristics associated with adherence. Evidence of concerning levels of non-adherence for some food/drink items suggests a case for more education on some of the guidance, particularly for women with lower educational attainment, greater parity and greater maternal age. Further research on barriers to the implementation of the guidance is needed.

Toxicological Risk Evaluation of Polycyclic Aromatic Hydrocarbons in Soils from a Petroleum Spillage Site at Kokori in the Niger Delta Region of Nigeria

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants that are produced by the incomplete combustion of organic sources and are widely found in soils. This present research was carried out to evaluate the concentrations and toxicological risk assessment of the United States Environmental Protection Agency's sixteen priority polycyclic aromatic hydrocarbons (16 priority PAHs) in soils from the vicinity of an oil spillage site in Delta State of Nigeria. The level of pollution and potential toxicological health hazards of the PAHs were assessed in surface soil samples using soxhlet extraction of and Gas Chromatography-Mass Spectrometry (GC-MS). Thirteen out of the sixteen USEPA priority PAHs were detected in the soil sample. The concentrations of PAHs in the petroleum-contaminated soils in this investigation ranged from 0.01181 ppm to 1.16054 ppm, with the total estimated concentration of the 16 priority PAHs being 5.6713 ppm. Furthermore, the distribution of the PAHs in the study area was predominated by LMW PAHs (62%) over HMW PAHs (38%). Additionally, the total toxicity equivalency quotients TEQ (B[a]Peq) result of the carcinogenic potency of the USEPA priority PAHs was calculated as 0.08689 ppm (8.689%) and was discovered to be within the Canadian TEQ (B[a]Peq) threshold of 0.6 ppm. This suggests that the soil in the study area is safe based on the Canadian TEQ (B[a]Peq) standard and does not constitute a carcinogenic risk. However, the long-term bioaccumulation of these low quantities of PAHs in human has been found to constitute a potential health concern due to bioaccumulation in living systems.

Characterizing extractables and leachables chemical space to support in silico toxicological hazard assessments

Characterizing extractables and leachables chemical space to support in silico toxicological hazard assessments

Chocolate toxicosis in pets

Chocolate ingestion is very common in pets, particularly dogs, but has also been reported in other animals including cats and rabbits. Most cases occur around Christmas and Easter, when large amounts of chocolate are often present in the home in the form of chocolate bars, snacks, confectionery, Easter eggs and chocolate figurines. Chocolate-covered raisins, nuts and coffee beans present an additional toxicological hazard in dogs. The type of chocolate is defined in law by the percentage of cocoa solids, with dark (plain) chocolate containing more than milk chocolate. The main toxic component of chocolate is theobromine, a methylxanthine, although caffeine, another methylxanthine, is also present. These cause central nervous system stimulation with cardiac and respiratory hyperactivity. Signs include gastrointestinal effects, excitability, hyperactivity, tachycardia, tremors, hypertension and hyperthermia. Signs of toxicosis generally occur within a few hours of ingestion. The mainstays of treatment are decontamination and supportive care with rehydration, control of central nervous system stimulation and arrhythmias as required. Most pets recover fully, and death is uncommon; however, prognosis is more guarded in pets with seizures or arrhythmias.

Content of Lead and Cadmium in the Tissues and Organs of the Wild Mallard Duck (Anas platyrhynchos L.) Depending on the Region of Poland Where It Is Harvested.

A property common to heavy metals is that even in small concentrations they can exert toxic effects on living organisms, including humans. The aim of this study was to analyze the quality of the tissues and organs of wild mallard ducks (Anas platyrhynchos L.) by estimating the potential hygiene and toxicological hazard associated with the concentrations of lead and cadmium in these tissues and organs, as well as the influence of the birds' sex and place of origin on these parameters. A significantly higher average lead content was noted in the breast muscles and the livers of the mallards harvested in the Leszno hunting district compared to the birds from the Siedlce hunting district. A higher average cadmium concentration was recorded in the breast and leg muscles of the mallards harvested in the Leszno hunting district than the Siedlce hunting district. The concentration of cadmium in the tissues and organs of the mallards harvested in the Siedlce or the Leszno hunting district did not exceed the acceptable limits for the muscles and livers of slaughtered animals. This study found no significant effect of the sex of the wild crossbreeds on the content of lead and cadmium in tissues and organs. This study showed that the mallard has a measurable response to environmental pollution with lead and cadmium, and therefore it is a species that could to some extent be used as a bioindicator of the level of contamination of the environment with these xenobiotics. The ban on the use of lead pellets as ammunition in Poland may largely limit the degree of lead contamination of the tissues and organs of mallards.

A multidimensional optimization strategy of pyraclostrobin-loaded microcapsules to improve the selectivity between toxicological risk in zebrafish and efficacy in controlling rice blast

Developing microcapsules (MCs) delivery systems can effectively mitigate toxicological risk of highly active/toxic pesticides; whereas the controlled release functions also limiting their practical effectiveness. Therefore, designing a precise regulating strategy to balance the toxicity and bioactivity of MCs is urgently needed. Here, we prepared a series of pyraclostrobin-loaded MCs with different wall materials, particle sizes, core density and shell compactness using interfacial polymerization. The results showed that the MCs released more slowly in water with increasing particle sizes and capsule compactness, and they sunk more quickly with the increasing particle sizes and core density. Additionally, MCs with slower release speed was always accompanied with lower acute toxicity levels to zebrafish. When the release dynamics slowed down to the threshold dose on demand for disease control, facilitating settlement of MCs can further reduce toxicity within spatial and temporal dimensions. The poor accumulation of MCs with larger particle sizes or dense shell in gills was closely related to their efficient detoxification. Importantly, seven of the MCs samples possessed superior selectivity between bio-performance in controlling rice blast and toxicological hazard to fish compared to commercial formulations. The results provide a comprehensive guidance for developing an efficient and safe pesticide delivery system.

Investigation on the skin penetration of synthetic amorphous silica (SAS) used in cosmetic products

Synthetic amorphous silica (SAS) is used as additive in a variety of industrial applications for many decades and has been approved to be used in food, food contact materials, pharmaceuticals, and cosmetics. Due its internal structure, SAS is considered as a nanomaterial, thus it is affected by a general safety discussion. Based on the production process, SAS for cosmetic application is a nanomaterial by the EU Recommendation, although it was not considered as such, because the solely size-dependent definitions of the term “nanomaterial” emerged in recent times first in Recommendation 2011/696/EU. Therefore, former physicochemical and toxicological evaluations of SAS were already performed on nanomaterials, however, without being addressed as such. Safety concerns can only emerge if two criteria, (toxicological) hazard and exposure towards the substance is fulfilled at the same time. In case of SAS, the Scientific Committee on Consumer Safety (SCCS) challenged provided data to be insufficient to draw a conclusion regarding the safety of SAS and thus, requested further investigations, in particular by exploring skin penetration of particulate SAS.Investigation of specific particulate substances in skin penetration tests is an analytical challenge. The number of available analytical techniques that are capable to detect nanomaterials in complex matrices, like receptor fluids from skin penetration testing, are limited and still emerging. In the new studies, a comprehensive set of analytical techniques were used to investigate the skin penetration potential of SAS. Particle-sensitive, element and particle-specific combinations of techniques and different sample preparation procedures, that respected the particulate nature of SAS, were used to detect SAS in receptor fluids directly. In addition, electron microscopic techniques were used to examine different layers of skin to detect adsorbed SAS.The combination of Asymmetric Flow Field-Flow Fractionation (AF4) in combination with Inductively Coupled Plasma Mass Spectrometry (ICP-MS) for examination of receptor fluids and Scanning Electron Microscopy coupled with Energy Dispersive X-ray spectroscopy (SEM/EDX) for examination of skin itself, were identified as suitable techniques for the detection of SAS in skin penetration tests. Data from literature was used to compare the results of the studies with the outcome of other test systems (other particles, other techniques). Both, the test results, and literature evaluation led to the conclusion, that SAS does not penetrate skin. Based on this outcome and local and systemic dermal toxicity review of SAS, it can be concluded that dermal application of SAS in cosmetic formulations is negligible.