Margin Of Exposure Research Articles

Determination and health risk assessment of acrylamide levels in instant coffee products available in Tehran markets by GC-MS

ABSTRACT This study aimed primarily to evaluate acrylamide (AA) concentration using rapid, simplified, cost-effective liquid-liquid extraction and gas chromatography-mass spectrometry (GC-MS) in the most common instant coffee products, and secondly, to calculate the health risk assessment of AA for adults and children. The acrylamide level was quantified using gas chromatography coupled with the mass spectrometry (GC-MS). The estimated daily intake (EDI), hazard quotient (HQ), and margin of exposure(MOE) was also calculated. According to the results, acrylamide levels in instant coffee were obtained between 0.5 to 440.9 μg/kg. The concentrations of acrylamide detected in all samples were below the recommended benchmark levels by the European Commission (<850 µg/kg). The overall mean was calculated 137.3 ± 25.7 for coffee mix powder samples and 154.8 ± 39.7 for pure powder samples. There was no significant difference in AA concentration between pure powder and coffee mix groups (P > 0.05). However, a significant difference in AA content was observed in different brands of pure powder as well as some groups of the coffee mix (P < 0.05). Furthermore, the health risk due to consumption of various type of coffee is negligible.

Dietary Exposure and Risk Assessment of Mycotoxins in Thyme and Thyme-Based Products Marketed in Lebanon.

This study aimed at evaluating the incidence of aflatoxin B1 (AFB1) and ochratoxin A (OTA) in thyme and thyme-based products, related dietary exposure, and cancer risk for regular and high consumption. A total of 160 samples were collected, and 32 composite samples were analyzed. AFB1 and OTA were respectively found in 84% (27/32) and 38% (12/32) of the samples. AFB1 exceeded the limits in 41% (13/32) and 25% (8/32) of the samples according to the Lebanese and European standards, respectively. OTA was unacceptable in only 6% (2/32) and 3% (1/32) of the samples according to the Lebanese and European standards, respectively. AFB1 and OTA daily exposure was shown to be 4.270 and 1.345 ng/kg bw/day, respectively. AFB1 was shown to be associated with 0.41 and 0.35 additional cancer cases per 100,000 persons per year for regular consumption, respectively; while for high consumption, an increase of 0.911 and 0.639 cancer cases per 100,000 person per year was noted, respectively. The margin of exposure (MOE) for OTA was >10,000 for the non-neoplastic effect and >200 for the neoplastic effect, representing no toxicological concerns for consumers.

Mycotoxin Exposure in Children through Breakfast Cereal Consumption in Chile.

Mycotoxins are unavoidable contaminants produced by fungi in food, especially grains. This study aimed to measure the occurrence and levels of total aflatoxins (AFs); ochratoxin A (OTA); zearalenone (ZEN); fumonisins B1, B2, and B3 (FUM); deoxynivalenol (DON); and T-2/HT-2 toxins in the four most commonly consumed breakfast cereals in Chile and to assess mycotoxin exposure and risk in children aged 2 to 13 years due to cereal consumption. In this study, a total of 110 batches with three subsamples of the four brands were sampled in supermarkets from November 2019 to June 2021. Samples were analyzed by Veratox® ELISA (Neogen). Exposure was assessed by estimated daily intake (EDI) considering the levels found in a modified lower bound (mLB) and upper bound (UB). Risk was estimated by margin of exposure (MOE) in the case of OTA and AFs and hazard quotient (HQ) for the rest of the mycotoxins. No T2/HT2 toxins were detected. Few samples had quantifiable levels of ZEN, FUM, and DON except for brand 1, with a mean (standard deviation, SD) of 54 (20), 1552 (351), and 706 (218) ng/g, respectively. In addition, three FUM samples and one DON sample had values over the Chilean regulation. Brands 2, 3, and 4 had quantifiable levels of AFs, with mean (SD) values of 1.3 (0.1), 2.1 (0.6), and 1.9 (0.4) ng/g, respectively. Brand 3 had quantifiable levels of OTA, with a mean (SD) of 2.3 (0.4) ng/g. Estimated exposure indicated a risk of AFs in all scenarios, and of FUM for brand 1 consumption, OTA and DON for brand 3 consumption, and OTA for brand 4 consumption in the mLB worst-case scenario. In general, mycotoxin levels were below the Chilean regulatory limits, but most of them were above the EU regulation for processed cereal-based food in young children. Because the risk was higher in the 2- to 5-year-old children, we recommend special regulations for this group in Chile.

Assessment of the genotoxicity of acrylamide.

EFSA was requested to deliver a statement on a recent publication revisiting the evidence for genotoxicity of acrylamide (AA). The statement was prepared by a Working Group and was endorsed by the CONTAM Panel before its final approval. In interpreting the Terms of Reference, the statement considered the modes of action underlying the carcinogenicity of AA including genotoxic and non‐genotoxic effects. Relevant publications since the 2015 CONTAM Panel Opinion on AA in food were reviewed. Several new studies reported positive results on the clastogenic and mutagenic properties of AA and its active metabolite glycidamide (GA). DNA adducts of GA were induced by AA exposure in experimental animals and have also been observed in humans. In addition to the genotoxicity of AA, there is evidence for both secondary DNA oxidation via generation of reactive oxygen species and for non‐genotoxic effects which may contribute to carcinogenesis by AA. These studies extend the information assessed by the CONTAM Panel in its 2015 Opinion, and support its conclusions. That Opinion applied the margin of exposure (MOE) approach, as recommended in the EFSA Guidance for substances that are both genotoxic and carcinogenic, for risk characterisation of the neoplastic effects of AA. Based on the new data evaluated, the MOE approach is still considered appropriate, and an update of the 2015 Opinion is not required at the present time.

Aflatoxin B1 Occurrence in Children under the Age of Five's Food Products and Aflatoxin M1 Exposure Assessment and Risk Characterization of Arab Infants through Consumption of Infant Powdered Formula: A Lebanese Experience.

Aflatoxin M1 (AFM1) is a salient metabolite that can be used to assess Aflatoxin B1 (AFB1) exposure in humans and animals. The carcinogenic potency of AFB1 and AFM1 was severely reported. The aims of this study were (1) to survey the contamination level of AFM1 in the most traded infant powdered formula brands (IPF) (n = 42) along with the AFB1 level in under 5’s children food brands (biscuits, cornflakes, and cereals) (n = 42) and (2) to assess the estimated daily intake (EDI), the hazard quotient (HQ) and the margin of exposure (MOE) of AFM1 among infants (0–12 months) in Lebanon. All of the samples were analyzed using ELISA technique. AFB1 was below detection limit in all of the children’s food brands samples. Out of 42 IPF samples 9.5% were AFM1-positive in the range of 29.54–140.16 ng/L and exceeded the maximum tolerable limit (MTL) set by the European commission (25 ng/kg). The overall average contamination level was 5.72 ± 0.014 ng/L. The EDI of AMF1 for male was in the range of 0.37–0.78 ng/kg/b.w./day and 0.40–0.87 ng/kg/b.w./day for females. Similarly, the HQ calculation resulted in an average of 3.05 for males and 3.28 for females. MOE calculations were far lower from 10,000 in both genders which indicates a high risk of genotoxicity and carcinogenicity. Our findings show that AFM1’s EDI, HQ and MOE scored high among Lebanese infants. As infants consume more IPF relative to their body weight, the persistence of IPF with high AFM1 levels threatens their health. Thus, infant’s exposure risk to AFM1 in IPF should be a continuous focus of attention.

Exposure assessment and risk-based limit levels evaluation of ochratoxin A in Astragali Radix in China

Ochratoxin A (OTA) is a mycotoxin found in a variety of foods and herbal medicines, and several governmental bodies around the world have set maximum allowable levels of OTA in different foods and herbal medicines. This study aims to evaluate the health risk of OTA in Astragali Radix (AR) in China, and to evaluate the effects of different limit levels on the risk control of OTA in AR. The concentrations of OTA in 187 samples of AR were investigated, and 61 (32.6%) samples were positive. The mean, 50th and 95th percentile values of OTA in positive samples were 56.2, 5.1 and 304.5 μg/kg, respectively. A margin of exposure (MOE) approach was applied to assess the risk. Considering other food sources, long-term consumers have a relatively high risk of OTA exposure due to the ingestion of AR. Theoretical limit levels of OTA in AR were evaluated from two dimensions by weighing the costs and the benefits. The results indicated that the limit levels that might be applied to the management of OTA contamination in AR in China could be screened out through risk-based evaluation of limit levels.

The Effect of Monitoring System on Risk Assessment of Aflatoxins in Iran's Pistachio Nuts Exported to the E.U. During 2012 - 2018.

Pistachio has high nutritional value and popularity. The susceptibility of pistachio to aflatoxin contamination caused establishing a monitoring system introduced and implemented by the Ministry of Health in Iran to ensure consumers' access to safe and hygienic pistachios. In this research, aflatoxin contamination level in all consignments (7298) exporting to E.U. was examined using HPLC with fluorescence detection after immunoaffinity column clean up from Nov 2012 to Oct 2018. The average recoveries ranged 78.6% - 97.6%, with a relative standard deviation for reproducibility below 8.5% and expanded uncertainty of aflatoxin B1 (AFB1) at spiked levels 1, 4, and 8 ng/g were 0.17, 0.57, 0.89 ng/g, respectively. The results showed that aflatoxin B1 and total (AFT) were detected in 1921 (23.4%) and 1927 cases (23.5%), with the mean values ranging from 2.18 - 4.6 ng/g and 2.8 - 5.1 ng/g during six consecutive years, respectively. Implementing an effective monitoring system for pistachio nuts could determine consignments contaminated with aflatoxins. Concerning AFB1, risk assessments recorded for dietary exposure dose, margin of exposure (MOE), Hazard Index (HI), estimated liver cancer risk, and cancer incidence attributable to dietary ranged 0.0132 - 0.1180 ng/kg.bw/day, 1441 - 12843, 0.21 - 1.84, 0.00071 - 0.00633 cases/105 population/year, 0.02 - 0.2%, respectively. Identification and rejection of contaminated cargos lead to an increase in MOE (> 10000), and it also guarantees that pistachio consumption is safe from a toxicology point of view. Due to the monitoring system, the estimation of liver cancer incidence attributable to dietary AFB1 was reduced (≤ 0.02%). It indicates that the consumption of pistachio poses no health risk for Europeans and Iranians.

RIFM fragrance ingredient safety assessment, l-carvone, CAS Registry Number 6485-40-1

l-Carvone was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that l-carvone is not genotoxic and provided a No Expected Sensitization Induction Level (NESIL) of 2600 μg/cm2 for the skin sensitization endpoint. Data on l-carvone provided a calculated Margin of Exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. The phototoxicity/photoallergenicity endpoint was completed based on data and ultraviolet/visible (UV/Vis) spectra; l-carvone is not phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class II material (0.47 mg/day); the exposure to l-carvone is below the TTC. The environmental endpoints were evaluated; l-carvone was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

Analysis of furan and its major furan derivatives in coffee products on the Chinese market using HS-GC–MS and the estimated exposure of the Chinese population

The current study analysed concentrations of furan and its derivatives in coffee products commercially available in China based on an improved headspace gas chromatography-mass spectrometry (HS-GC–MS) method and estimated health risks. A total of 101 samples of coffee products on the Chinese market was analysed. Furan (98%, ND-6569 μg/kg) and 2-methylfuran (100%, 2–29639 μg/kg) were the compounds with the highest concentrations and detection rates in coffee products. The mean dietary exposure of Chinese consumers to furan and the sum of furan, 2-methylfuran and 3-methylfuran in coffee products was 0.09 and 0.46 μg/kg bw/day, respectively. For the neoplastic effects of furan, the margin of exposure (MOE) was 14,556 for the mean dietary exposure of consumers. For the non-neoplastic effects of furan, MOEs were 711 and 139 for furan and the sum of furan, 2-methylfuran and 3-methylfuran, respectively. Overall, a health concern is indicated for coffee consumers with MOEs below 10000.

Prediction of tissue and urine concentrations of 2-phenoxyethanol and its metabolite 2-phenoxyacetic acid in rat and human after oral and dermal exposures via GastroPlusTM physiologically based pharmacokinetic modelling

ABSTRACT A physiologically based pharmacokinetic (PBPK) model for the important chemical phenoxyethanol (PhE) and its metabolite phenoxyacetic acid (PhAA) was built via GastroPlusTM software (version 9.0) using currently available analytically measured plasma and urinary time-courses of both PhE and its metabolite PhAA. This model was validated and used to predict tissue and urine concentrations of PhE and its metabolite PhAA in rats and humans after oral and dermal exposures. The prediction results showed that most predicted tissue concentrations of PhE or PhAA were lower than the experimental tissue concentrations based on total radioactivity. The predicted cumulative excretion of PhAA in both rats and humans fits very well with most experimental data. With this GastroPlusTM-based model, the margins of exposure (MOE) of PhE and PhAA were also calculated as 194 and 73.7, respectively. The predicted MOE of PhE is two-fold higher than the previous PBPK model built using total radioactivity-based tissue time courses, and the predicted MOE of PhAA was comparable to the previous PBPK model. These data indicate that for chemicals like PhE, GastroPlusTM can integrate multiple data sets into PBPK models to predict PK parameters for parent and metabolites in both rats and humans following intravenous, dermal, or oral exposures.

Risk assessment of potentially toxic trace elements via consumption of dairy products sold in the city of Yerevan, Armenia

The study aimed to investigate the potentially toxic trace elements (PTEs) Pb, Cd, Hg, Mo, and Cu in dairy products sold in Yerevan's markets and to assess the related exposure and possible health risks among the adult population residing in the capital city of Armenia, Yerevan.The PTEs contents were determined in widely consumed dairy products (pasteurized milk, sour cream, matsoun and cheese from cow milk) using graphite furnace atomic absorption spectrometry. PTE contents were in the range of 7.90E-04 (Pb in pasteurized milk) to 6.75E-01 (Cu in cheese) mg/kg. Food consumption was assessed by the 24-h dietary recall method. The PTE daily intakes and margin of exposure (MOE) were calculated by the deterministic approach.The results indicated potential health concerns for the contribution of dairy products to the overall dietary intake of Pb and Cd. MOEs of Pb and Cd (8.71 and 8.80, respectively) estimated for high consumers of cheese (90 g/day and more) were lower than 10. The pilot data set provides the first comprehensive appraisal on the dairy products contamination by PTEs in the Caucasus region. The results point out further attention to sources of Pb and Cd in Armenian dairy products, including environment and farm characteristics.

Prevalence of Aflatoxins in Selected Dry Fruits, Impact of Storage Conditions on Contamination Levels and Associated Health Risks on Pakistani Consumers.

Dry fruits and nuts are nutritious foods with several health-promoting properties. However, they are prone to contamination with aflatoxins at all stages of production and storage. The present study aimed to determine the natural occurrence of aflatoxin B1 (AFB1), aflatoxin B2 (AFB2), aflatoxin G1 (AFG1), aflatoxin G2 (AFG2), and total aflatoxins (AFT) in dates, pistachios, and walnuts collected from four districts of South Punjab (Pakistan), and to assess the associated health risks as estimated by dietary exposure and the Margin of Exposure (MoE) determinations. The contents of AFB1 and AFT in these food products were monitored during storage under three different conditions (open-air, hermetically closed jars, and refrigeration at 4 °C) to determine the most efficient conditions in preventing aflatoxin accumulation. HPLC-fluorescence analysis of 60 samples of these products for aflatoxin contamination showed that 52 (86.7%) samples were contaminated at different levels, with a maximum of 24.2 ng/g. The overall (all samples) mean concentrations of AFB1, AFB2, AFG1, AFG2, and AFT were 3.39 ± 2.96, 1.39 ± 1.68, 1.63 ± 1.48. 1.12 ± 1.23, and 7.54 ± 6.68, respectively. The Estimated Daily Intake (EDI) and MoE of aflatoxins through the consumption of the products ranged from 0.06 ng/kg bw/day to 2.0 ng/kg bw/day and from 84.84 to 2857.13, respectively, indicating that consumers are at high health risk. Significant differences were recorded between aflatoxin levels in the samples stored under different storage conditions, with storage under refrigeration (4 °C) being the most effective in controlling aflatoxin accumulation, although storage in closed jars was also efficient and offers a more flexible alternative to retailers. The findings of the study urge official authorities of Pakistan to implement appropriate regulatory and control measures and surveillance program to alleviate the potential public health risks associated with the consumption of dry fruits and nuts in the scope of their increased consumption.

Risk characterization of dietary acrylamide exposure and associated factors in the Portuguese population

Acrylamide exposure, mainly resulting from food cooking and processing, has been associated with a higher risk of health problems, due to genotoxic effects. This study aims to estimate acrylamide dietary exposure of the Portuguese population and its associated factors. Dietary data collected through 2 non-consecutive 24 hour recalls or food diaries from a representative sample of the Portuguese population from the National Food, Nutrition and Physical Activity Survey was used (n = 5811; 3–84 years). Occurrence data of acrylamide in food were obtained from EFSA. The margins of exposure (MOE) were calculated for peripheral neuropathy and neoplastic effects. The association between acrylamide and socio-demographic characteristics was estimated through linear regression models. For the total population, the estimated median daily dietary exposure per body weight to acrylamide was 0.38 µg/kg/day, ranging from 0.14 to 0.88 µg/kg/day for the 5th and 95th percentile, respectively. Children aged between 1–2 years had the highest acrylamide exposure (median 0.75 µg/kg/day, 95th percentile 1.41 µg/kg/day). For the peripheral neuropathy and neoplastic effects, the median MOE estimated was 1140 and 451, respectively. Men compared to women had a higher acrylamide dietary exposure, as well as smokers compared to non-smokers. Elderly and less educated individuals were inversely associated with acrylamide exposure. ‘Bread and rusks’ (24.2%) were the main source of acrylamide, followed by ‘coffee’ (21.3%). The current dietary exposure to acrylamide in the Portuguese population is of concern mainly regarding neoplastic effects. Our results point to the need to reduce exposure to acrylamide, especially in men, young children, higher educated individuals and smokers.

Determination of Polycyclic Aromatic Hydrocarbons in Traditional Chinese Medicine Raw Material, Extracts, and Health Food Products.

The four polycyclic aromatic hydrocarbon markers (PAH4) of benzo[a]anthracene (BaA), chrysene (Chr), benzo[b]fluoranthene (BbF), and benzo[a]pyrene (BaP) are indicators showing polycyclic aromatic hydrocarbon (PAH) contamination levels in Chinese medicine raw materials (CMRMs), extracts and health food products; Samples of herbal medicine, herbal extracts, and food supplements were extracted with n-hexane, then cleaned up sequentially on Florisil and EUPAH solid-phase extraction (SPE) columns. A gas chromatography–mass spectrometry method for the determination of four polycyclic aromatic hydrocarbon markers in Chinese medicine raw material, extracts, and health food products was established; In spiked-recovery experiments, the average recovery was about 78.6–107.6% with a precision of 2.3–10.5%. The limit of quantification (LOQ) and limit of detection (LOD) of the PAH4 markers in this method were 2.0 μg/kg and 0.7 μg/kg, respectively. When the developed method was utilized to determine PAH4 contents in 12 locally available health food products, 3 samples contained over 10.0 μg/kg BaP, and 5 samples contained over 50.0 μg/kg PAH4. The European Union (EU) limits for BaP and PAH4 are 10 and 50.0 μg/kg, respectively; therefore, more attention must be drawn to the exposure risk of BaP and PAH4 in CMRMs, their extracts, and health food products. According to the risk assessment based on the Margin of Exposure (MOE) method, it is recognized that the products mentioned in this study pose a low risk.

Dose and exposure route analyses inform relationships between liver steatosis and 2-amino-2-methyl-1-propanol: Implications for hazard characterization.

2-Amino-2-methyl-1-propanol (AMP™) is widely used as a neutralizer/pH stabilizer in personal care products (PCPs); however, the potential health implications of dermal AMP exposure remain to be fully elucidated. Consequently, an in-depth analysis was performed to determine if PCPs containing AMP pose an elevated risk in humans under the intended use conditions. Animal studies have shown that at high doses, oral AMP exposure could lead to liver steatosis; thus, this study focused on hepatotoxicity. Our assessment revealed that the derived margin of exposure (MoE) values for AMP-containing PCPs were above 100, indicating that dermal exposure to AMP is unlikely to present an elevated risk of hepatotoxicity. Further, mode of action (MOA) analysis was conducted to elucidate the potential mechanisms underlying the observed hepatotoxicity in animal studies. Our analysis proposed that AMP interferes with the CDP-choline pathway in hepatocytes via the inhibition of one or more enzymes integral to the pathway and/or the replacement of choline in the assembly of the phospholipid unit. Ultimately, these events halt the lipid export via very low-density lipoproteins, which can subsequently develop into fatty liver accompanied by hepatotoxicity and other pathological changes if AMP exposure persists at sufficiently high doses. MOA analysis corroborated that dermal exposure to AMP expected from use of PCPs is highly unlikely to result in toxicologically significant systemic concentrations of AMP and thus hepatotoxicity. We concluded that dermal exposure to AMP in PCPs is not anticipated to result in an increased risk of hepatotoxicity.

Technical Report on the notification of xuta (edible variety of Jatropha curcas L.) roasted and ground seed kernels as a traditional food from a third country pursuant to Article 14 of Regulation (EU) 2015/2283

A notification from Jatropower AG (Switzerland) was submitted to the European Commission under Article 14 of Regulation (EU) 2015/2283 to place on the market xuta (edible variety of Jatropha curcas L.) roasted and ground seed kernels as a traditional food from a third country (TF). In line with Article 15(2) of that Regulation, EFSA was asked by the European Commission whether there are duly reasoned safety objections to the placing on the market of the TF within the European Union. In the compositional analyses phorbol esters (PEs) were reported to be below the detection limit in five batches of raw xuta powder. PEs represent the potential major hazard in the use of Jatropha kernels and thus in the TF. PEs do not induce tumours per se but promote tumour growth and may act as cocarcinogens. Despite the measures implemented by the applicant to select edible Jatropha plants and to analyse the TF for PEs, low levels might still be present in the flour. In 2015 the CONTAM Panel assessed the toxicity of PEs in non-edible Jatropha kernel meals and identified a no observed adverse effect level (NOAEL) for PEs. The CONTAM Panel concluded that due to limitations in the toxicological dataset and the characteristics of PEs (protein kinase C activation and structural alert for genotoxicity), a sufficient margin of exposure (MOE) was not defined. Taking into account (i) the insufficient information on the intended uses and use levels of the TF to allow for a proper intake exposure assessment, (ii) the resulting impossibility to calculate a MOE based on the NOAEL for PEs, and (iii) the limited knowledge and the uncertainties regarding the genotoxic potential of PEs and thus of the TF, EFSA considers that the TF may pose a safety risk to human health. Thus, EFSA raises safety objections to the placing on the market within the EU of the TF.

RIFM fragrance ingredient safety assessment, 2,6-nonadienenitrile, CAS Registry Number 67019-89-0

The existing information supports the use of this material as described in this safety assessment. 2,6-Nonadienenitrile was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that 2,6-nonadienenitrile is not genotoxic. Data on read-across analog E- and Z-2(+3),12-tridecadiennitrile (CAS # 124071-40-5) provided 2,6-nonadienenitrile a calculated Margin of Exposure (MOE) > 100 for the repeated dose toxicity endpoint. The reproductive and local respiratory toxicity endpoints were evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class III material, and the exposure to 2,6-nonadienenitrile is below the TTC (0.0015 mg/kg/day and 0.47 mg/day, respectively). Data show that there are no safety concerns for 2,6-nonadienenitrile for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet/visible (UV/Vis) spectra; 2,6-nonadienenitrile is not expected to be phototoxic/photoallergenic. The environmental endpoints were evaluated; 2,6-nonadienenitrile was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

RIFM fragrance ingredient safety assessment, octyl isobutyrate, CAS Registry Number 109-15-9

The existing information supports the use of this material as described in this safety assessment. Octyl isobutyrate was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data from read-across analog hexyl isobutyrate (CAS # 2349-07-7) show that octyl isobutyrate is not expected to be genotoxic. Data on analog propyl (2S)-2-(1,1-dimethylpropoxy)-propanoate (CAS # 319002-92-1) provide a calculated Margin of Exposure (MOE) > 100 for the repeated dose and reproductive toxicity endpoints. Data from analog hexyl 2-methylbutyrate (CAS # 10032-15-2) provided octyl isobutyrate a No Expected Sensitization Induction Level (NESIL) of 7000 μg/cm2 for the skin sensitization endpoint. Octyl isobutyrate is not expected to be phototoxic/photoallergenic based on ultraviolet/visible (UV/Vis) spectra. The local respiratory toxicity endpoint was evaluated using the Threshold of Toxicological Concern (TTC) for a Cramer Class I material; exposure to is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; octyl isobutyrate was found not to be Persistent, Bioaccumulative, and Toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are <1.

Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Popular Disposable E-cigarettes: Chemical Analysis and Risk Assessment.

Menthol, through its cooling and pleasant sensory effects, facilitates smoking and tobacco product initiation, resulting in the high popularity of mint/menthol-flavored E-cigarettes. More recently, E-cigarette vendors started marketing synthetic cooling agents as additives that impart a cooling effect but lack a characteristic minty odor. Knowledge about content of synthetic coolants in US-marketed E-cigarette products and associated health risks is limited. E-liquid vendor sites were searched with the terms "koolada", "kool/cool", "ice", or WS-3/WS-23, denoting individual cooling agents, and relevant refill E-liquids were purchased. "Ice" flavor varieties of Puffbar, the most popular disposable E-cigarette brand, were compared with non-"Ice" varieties. E-liquids were characterized, and synthetic coolants quantified using GC/MS. Margin of exposure (MOE), a risk assessment parameter, was calculated to assess the risk associated with synthetic coolant exposure from E-cigarette use. WS-3 was detected in 24/25 refill E-liquids analyzed. All Puffbar flavor varieties contained either WS-23 (13/14) or WS-3 (5/14), in both "Ice"- and non-"Ice" flavors. Modeling consumption of WS-3 from vaped E-liquids, resulted in MOEs below the safe margin of 100 for most daily use scenarios. MOEs for WS-23 were <100 for 10/13 Puffbar flavors in all use scenarios. Puffbar power specifications are identical to Juul devices. Synthetic cooling agents (WS-3/WS-23) were present in US-marketed E-cigarettes, at levels that may result in consumer exposures exceeding safety thresholds set by regulatory agencies. Synthetic coolants are not only found in mint- or menthol-flavored products but also in fruit- and candy-flavored products, including popular disposable E-cigarette products such as Puffbar. Synthetic cooling agents are widely used in "kool/cool"- and "ice"-flavored E-liquids and in E-liquids without these labels, both as a potential replacement for menthol or to add cooling "notes" to nonmenthol flavors. These agents may be used to bypass current and future regulatory limits on menthol content in tobacco products, and not just E-cigarettes. Because synthetic cooling agents are odorless, they may not fall under the category of "characterizing flavor", potentially circumventing regulatory measures based on this concept. Regulators need to consider the additional health risks associated with exposure to synthetic cooling agents.

Risk assessment of uptake of trace elements through consumption of cereals: a pilot study in Yerevan, Armenia.

The study aimed to assess the dietary exposure and related human health risks associated with trace elements through the intake of staple cereals, including buckwheat, rice, and emmer. The contents of Lead (Pb), Cadmium (Cd), Mercury (Hg), Nickel (Ni), Molybdenum (Mo), Iron (Fe), and Copper (Cu) were determined using Atomic Absorption Spectrometry. Cereal consumption data were obtained through a Semi-Quantitative Food Frequency Questionnaire amongst the Yerevan adult population. Concentrations of Pb, Cd, Hg, Ni, Mo, Fe and Cu were 0.75-5.56µg/kg, 1.21-6µg/kg, 6.7-6.99µg/kg, 50.6-111µg/kg, 20-429µg/kg, 2770-30500µg/kg and 601-1720µg/kg respectively. The estimated daily intakes (EDI) of all studied trace elements did not exceed the health-based guidance values. The margin of exposure (MOE) values of Pb, Cd, Hg, and Mo for all clusters were above the threshold (>10 for Pb, Cd, and >100 for Hg, Mo) and therefore did not indicate a health concern. Meanwhile, in the case of Ni exposure, the MOE values for the second and third clusters of buckwheat consumption and for the third cluster of emmer consumption were below the threshold (<10) indicating that a human health risk cannot be excluded. Future work is proposed.