SpectraX: A Straightforward Tool for Principal Component Analysis-Based Spectral Analysis.

The analysis of complex spectra is an important component of direct/ambient mass spectrometry (MS) applications such as natural product screening. Unlike chromatography-based metabolomics or proteomics approaches, which rely on software and algorithms, the work of spectral screening is mostly performed manually in the initial stages of research and relies heavily on the experience of the analyst. As a result, throughput and spectral screening reliability are problematic when dealing with large amounts of data. Here, we present SpectraX, a MATLAB-based application, which can analyze MS spectra and quickly locate m/z features from them. Principal component analysis (PCA) is used to analyze the data set, and scoring plots are presented to help in understanding the clustering of data. The algorithm uses mass to charge (m/z) features to produce a list of potential natural products.

Scale up of anaesthesia services in underserved rural Tanzania.

BACKGROUND: Because of critical shortage of physician anaesthesiologists, the government of Tanzania adopted a task shifting strategy for provision of anaesthesia services. This paper describes the results of an operational study designed to increase the number of anaesthesia providers for emergency obstetric surgeries in order to reduce maternal and perinatal mortality in underserved rural Tanzania. METHODS: In 2016 a before-after cohort study was conducted in seven health centres in rural Tanzania. Five health centres received an intervention and two were selected to track secular trends (control group). Ten associate clinicians, i.e. assistant medical officers, clinical officers, and nurse midwives, from five health centres were trained in anaesthesia skills for emergency obstetric surgeries for three months followed by quarterly supportive supervision, mentoring and teleconsultation to reinforce skills. Primary and secondary outcome measures included Caesarean delivery (CD) rate, quality and safety of anaesthesia, and uptake of the educational program for anaesthesia. RESULTS: Out of the 2,179 CDs performed in the intervention facilities from 2016 to 2019, two women died from complications of anaesthesia. The risk of death from anaesthetic complications was 0.9 per 1000 CD (95% CI 0.1-3.3. The risk of death was not established in the control group because of inadequate documentation and records keeping. The proportion of CD performed under spinal anaesthesia in intervention facilities doubled from 28% (60/214 with 95% CI 22-35) at baseline (July 2014 - June 2016) to 57% (558/971 with 95% CI of 54-61) in year three (July 2018 - June 2019), while in the control group increased by only 40% from 19% (92/475 with 95% CI of 16-23) at baseline and 27% (68/251 with 95% CI of 22-33) in year three. In 2020I, this educational training program was then adopted by the government with minor content changes and increasing duration of training to six months. CONCLUSIONS: This three month educational training program for associate clinicians in anaesthesia, complemented by supportive supervision, can increase the CD rate to one that fills the "unmet need" and the proportion of operations performed under spinal anaesthesia, the gold standard technique for CD. The program can be used to meet the urgent demand for anaesthesia services in other underserved areas in Africa.

Rapid Mass Spectrometric Calibration and Standard Addition Using Hydrophobic/Hydrophilic Patterned Surfaces and Discontinuous Dewetting.

The rapid calibration chip (RCC) is a device that uses the fast and reproducible wetting behavior of hydrophilic/hydrophobic patterned surfaces to confine a series of differently sized droplets on a substrate to obtain a calibration curve. Multiple series of droplets can be formed within seconds by dipping an RCC into a calibration solution. No pipetting, sequential droplet deposition, or advanced equipment is required. The performance and reproducibility of RCCs were evaluated with an electrospray ionization triple-quadrupole mass spectrometer equipped with a liquid microjunction-surface sampling probe (LMJ-SSP) that allows for fast sampling of surfaces. Using circular hydrophilic areas with diameters ranging from 0.25 to 2.00 mm, liquid volumes of 4.6-70.6 nL could be deposited. Furthermore, the use of a second hydrophobic/hydrophilic patterned transfer chip can be used to add internal standard solutions to each calibration spot of the RCC, allowing to transfer a liquid volume of 22.5 nL.

Solvent effects on differentiation of mouse brain tissue using laser microdissection 'cut and drop' sampling with direct mass spectral analysis.

RATIONALE: Laser microdissection-liquid vortex capture/electrospray ionization mass spectrometry (LMD-LVC/ESI-MS) has potential for on-line classification of tissue but an investigation into what analytical conditions provide best spectral differentiation has not been conducted. The effects of solvent, ionization polarity, and spectral acquisition parameters on differentiation of mouse brain tissue regions are described. METHODS: Individual 40 × 40 µm microdissections from cortex, white, grey, granular, and nucleus regions of mouse brain tissue were analyzed using different capture/ESI solvents, in positive and negative ion mode ESI, using time-of-flight (TOF)-MS and sequential window acquisitions of all theoretical spectra (SWATH)-MS (a permutation of tandem-MS), and combinations thereof. Principal component analysis-linear discriminant analysis (PCA-LDA), applied to each mass spectral dataset, was used to determine the accuracy of differentiation of mouse brain tissue regions. RESULTS: Mass spectral differences associated with capture/ESI solvent composition manifested as altered relative distributions of ions rather than the presence or absence of unique ions. In negative ion mode ESI, 80/20 (v/v) methanol/water yielded spectra with low signal/noise ratios relative to other solvents. PCA-LDA models acquired using 90/10 (v/v) methanol/chloroform differentiated tissue regions with 100% accuracy while data collected using methanol misclassified some samples. The combination of SWATH-MS and TOF-MS data improved differentiation accuracy. CONCLUSIONS: Combined TOF-MS and SWATH-MS data differentiated white, grey, granular, and nucleus mouse tissue regions with greater accuracy than when solely using TOF-MS data. Using 90/10 (v/v) methanol/chloroform, tissue regions were perfectly differentiated. These results will guide future studies looking to utilize the potential of LMD-LVC/ESI-MS for tissue and disease differentiation.

Hyphenation of Production-Scale Free-Flow Electrophoresis to Electrospray Ionization Mass Spectrometry Using a Highly Conductive Background Electrolyte.

In this technical note, we demonstrate the hyphenation of production-scale free-flow electrophoresis (FFE) and sheathless electrospray ionization mass spectrometry (ESI-MS). In contrast to previous hyphenation approaches, we used a highly conductive background electrolyte (BGE) required for production-scale FFE. We found that this kind of BGE as well as a production-scale setup leads to significant electric interference between FFE and MS. This interference prevents steady-state FFE operation. We examine this interference in detail and discuss possible solutions to this issue. We demonstrate that the straightforward grounding of the transfer line removes the influence of ESI-MS on FFE, but creates a current leak from the ESI interface, which adversely affects the ESI spray. Furthermore, we show that only the electrical disconnection of the ESI probe from the FFE-MS transfer line suppresses this undesirable current. In order to facilitate the electrical disconnection we used a low conductivity, silica-based ESI probe with withdrawn inner capillary. This approach allowed the interference-free hyphenation of production-scale FFE (using a highly conductive BGE) with ESI-MS.

Kinetic size-exclusion chromatography with mass spectrometry detection: an approach for solution-based label-free kinetic analysis of protein-small molecule interactions.

Studying the kinetics of reversible protein-small molecule binding is a major challenge. The available approaches require that either the small molecule or the protein be modified by labeling or immobilization on a surface. Not only can such modifications be difficult to do but also they can drastically affect the kinetic parameters of the interaction. To solve this problem, we present kinetic size-exclusion chromatography with mass spectrometry detection (KSEC-MS), a solution-based label-free approach. KSEC-MS utilizes the ability of size-exclusion chromatography (SEC) to separate any small molecule from any protein-small molecule complex without immobilization and the ability of mass spectrometry (MS) to detect a small molecule without a label. The rate constants of complex formation and dissociation are deconvoluted from the temporal pattern of small molecule elution measured with MS at the exit from the SEC column. This work describes the concept of KSEC-MS and proves it in principle by measuring the rate constants of interaction between carbonic anhydrase and acetazolamide.

Development and validation of a specific and sensitive gas chromatography tandem mass spectrometry method for the determination of bisphenol A residues in a large set of food items.

BPA-containing products are widely used in foodstuffs packaging as authorized within the European Union (UE no. 10/2011). Therefore, foods and beverages are in contact with BPA which can migrate from food contact material to foodstuffs. An accurate assessment of the exposure of the consumers to BPA is crucial for a non-ambiguous risk characterization. In this context, an efficient analytical method using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS), in the selected reaction monitoring (SRM) mode, was developed for the quantification of BPA in foodstuffs at very low levels (<0.5µgkg(-1)). A standard operating procedure, based on the combination of two successive solid phase extractions (SPE), was developed for various liquid and solid foodstuffs. The use of (13)C12-BPA as internal standard allowed accurate quantification of BPA by isotopic dilution. Control charts based on both blank and certified materials have been implemented to ensure analytical data quality. The developed analytical method has been validated according to in-house validation requirements. R(2) was better than 0.9990 within the range [0-100µgkg(-1)], the trueness was 4.2%. Repeatability and within-laboratory reproducibility ranged from 7.5% to 19.0% and 2.5% to 12.2%, respectively, at 0.5 and 5.0µgkg(-1) depending on the matrices tested for. The detection and quantification limits were 0.03 and 0.10µgkg(-1), respectively. The reporting limit was 0.35µgkg(-1), taking into account the mean of the laboratory background contamination. The global uncertainty was 22.2% at 95% confidence interval.

Assessment of infant exposure to food chemicals: the French Total Diet Study design.

As part of the previous French Total Diet Studies (TDS) focusing on exposure to food chemicals in the population aged 3 years and older, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) launched a specific TDS on infants to complete its overall chemical food safety programme for the general population. More than 500 chemical substances were analysed in food products consumed by children under 3 years old, including nutrients, several endocrine disruptors resulting from human activities (polychlorinated biphenyls, dioxins and furans, brominated flame retardants, perfluoroalkyl acids, pesticide residues, etc.) or migrating from food contact materials such as bisphenol A or phthalates, but also natural substances such as mycotoxins, phytoestrogens and steroids. To obtain a representative and general view of infant food consumption, food items were selected based on results of a national consumption survey conducted specifically on this population. Moreover, a specific study on food was conducted on 429 households to determine which home-cooking practices are employed to prepare food consumed by infants. Overall, the targeted chemical substances were analysed in more than 450 food samples, representing the purchase and home-cooking practices of over 5500 food products. Foods included common foods such as vegetables, fruit or cakes as well as specific infant foods such as infant formula or jarred baby food. The sampling plan covered over 80% of the total diet. Specificities in infant food consumption and habits were therefore considered to define this first infant TDS. This study, conducted on a large scale and focusing on a particularly sensitive population, will provide accurate information on the dietary exposure of children under 3 years to food chemicals, especially endocrine disruptors, and will be particularly useful for risk assessment analysis under the remit of ANSES' expert committees.

Food risk assessment for perfluoroalkyl acids and brominated flame retardants in the French population: results from the second French total diet study.

To determine the exposure of the French population to toxic compounds contaminating the food chain, a total diet study was performed in France between 2007 and 2009. This study was designed to reflect the consumption habits of the French population and covered the most important foods in terms of consumption, selected nutrients and contribution to contamination. Based on French consumption data, the present study reports the dietary exposure to perfluoroalkyl acids (16 congeners) and brominated flame retardants (polybrominated diphenyl ethers, hexabromocyclododecane and polybrominated biphenyls). Comparison of the calculated dietary exposures with the generally accepted health-based guidance values revealed that most compounds do not pose any risk. There are however knowledge gaps for some congeners in these large chemical classes.

Dietary exposure to perfluoroalkyl acids of specific French adult sub-populations: high seafood consumers, high freshwater fish consumers and pregnant women.

Perfluoroalkyl acids (PFAAs) are globally found in various media, including food and especially fishery products. In the present study, the dietary exposure to 15 perfluoroalkyl acids was assessed for 3 French adult populations, namely high seafood consumers, high freshwater fish consumers, and pregnant women. Purified food extracts were analysed by LC-MS/MS and PFBA, PFPA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnA, PFTrDA, PFTeDA, PFBS, PFHxS, PFHpS, PFOS and PFDS were monitored and quantified according to the isotope dilution principle. Under lower bound (LB) hypothesis (i.e. contamination values

Dietary exposure and health risk assessment for 11 minerals and trace elements in Yaoundé: the Cameroonian Total Diet Study.

Dietary exposure to 11 elements was assessed by the Total Diet Study (TDS) method. Sixty-four pooled samples representing 96.5% of the diet in Yaoundé, Cameroon, were prepared as consumed before analysis. Consumption data were sourced from a household budget survey. Dietary exposures were compared with nutritional or health-based guidance values (HBGV) and to worldwide TDS results. Elevated prevalence of inadequate intake was estimated for calcium (71.6%), iron (89.7%), magnesium (31.8%), zinc (46.9%) and selenium (87.3%). The percentage of the study population exceeding the tolerable upper intake levels was estimated as <3.2% for calcium, iron, magnesium, zinc and cobalt; 19.1% of the population exceeded the HBGV for sodium. No exceedance of the HBGV for inorganic mercury was predicted in the population. The margin of exposure ranged from 0.91 to 25.0 for inorganic arsenic depending on the reference point. The "Fish" food group was the highest contributor to intake for calcium (65%), cobalt (32%) and selenium (96%). This group was the highest contributor to the exposure to total arsenic (71%) and organic mercury (96%). The "Cereals and cereal products" highly contributed to iron (26%), zinc (26%) and chromium (25%) intakes. The "Tubers and starches" highly contributed to magnesium (39%) and potassium (52%) intakes. This study highlights the dietary deficiency of some essential elements and a low dietary exposure to toxic elements in Yaoundé.

Assessment of dietary exposure to annatto (E160b), nitrites (E249-250), sulphites (E220-228) and tartaric acid (E334) in the French population: the second French total diet study.

The results of the assessment of the dietary exposure to annatto, nitrites, tartaric acid and sulphites within the framework of the second French total diet study (TDS) are reported. These 4 additives were selected from the Bemrah et al. study [Bemrah N, Leblanc JC, Volatier JL. 2008. Assessment of dietary exposure in the French population to 13 selected food colours, preservatives, antioxidants, stabilizers, emulsifiers and sweeteners. Food Addit Contam B. 1(1):2-14] on 13 food additives which identified a possible health risk for annatto, sulphites and nitrites and a lack of data for tartaric acid. Among the composite samples selected for the whole TDS, 524 were analysed for additives (a sample was analysed for a given additive when it was identified as a major contributor for this additive only): 130 for tartaric acid, 135 for nitrites, 59 for annatto and 200 for sulphites. Estimated concentrations (minimum lower bound to maximum upper bound) vary nationally from 0 to 9 mg/kg for annatto, 0 to 420 mg/kg for tartaric acid, 0 to 108 mg/kg for sulphites and 0 to 3.4 mg/kg for nitrites. Based on the analytical results, the dietary exposure was calculated for adults and children, separately, using lower bound and upper bound assumptions. The European ADIs for these 4 additives were not exceeded except for the dietary exposure for sulphites among 2.9% of the adult population, where the major contributors were alcoholic drinks and especially wine under both hypotheses (lower and upper bound).

A restricted cubic spline approach to assess the association between high fat fish intake and red blood cell EPA + DHA content.

BACKGROUND AND AIMS: Fish, especially fatty fish, are the main contributor to eicosapentaenoic (EPA) and docosahexaenoic (DHA) intake. EPA and DHA concentrations in red blood cells (RBC) has been proposed as a cardiovascular risk factor, with <4% and >8% associated with the lowest and greatest protection, respectively. The relationship between high fat fish (HFF) intake and RBC EPA + DHA content has been little investigated on a wide range of fish intake, and may be non-linear. We aimed to study the shape of this relationship among high seafood consumers. METHODS AND RESULTS: Seafood consumption records and blood were collected from 384 French heavy seafood consumers and EPA and DHA were measured in RBC. A multivariate linear regression was performed using restricted cubic splines to consider potential non-linear associations. Thirty-six percent of subjects had an RBC EPA + DHA content lower than 4% and only 5% exceeded 8%. HFF consumption was significantly associated with RBC EPA + DHA content (P [overall association] = 0.021) adjusted for sex, tobacco status, study area, socioeconomic status, age, alcohol, other seafood, meat, and meat product intakes. This relationship was non-linear: for intakes higher than 200 g/wk, EPA + DHA content tended to stagnate. Tobacco status and fish contaminants were negatively associated with RBC EPA + DHA content. CONCLUSION: Because of the saturation for high intakes, and accounting for the concern with exposure to trace element contaminants, intake not exceeding 200 g should be considered.

Core food of the French food supply: second Total Diet Study.

As first described in the 1980s, the core food intake model allows a precise assessment of dietary nutrient intake and dietary exposure to contaminants insofar as it reflects the eating habits of a target population and covers the most important foods in terms of consumption, selected nutrient and contaminant contribution. This model has been used to set up the sampling strategy of the second French Total Diet Study (TDS) with the aim of obtaining a realistic panorama of nutrient intakes and contaminant exposure for the whole population, useful for quantitative risk assessment. Data on consumption trends and eating habits from the second French individual food consumption survey (INCA2) as well as data from a 2004 purchase panel of French households (SECODIP) were used to identify the core foods to be sampled. A total of 116 core foods on a national scale and 70 core foods on a regional scale were selected according to (1) the consumption data for adults and children, (2) their consumer rates, and (3) their high contribution to exposure to one or more contaminants of interest. Foods were collected in eight French regions (36 cities) and prepared 'as consumed' to be analysed for their nutritional composition and contamination levels. A total of 20 280 different food products were purchased to make up the 1352 composite samples of core foods to be analysed for additives, environmental contaminants, pesticide residues, trace elements and minerals, mycotoxins and acrylamide. The establishment of such a sampling plan is essential for effective, high-quality monitoring of dietary exposure from a public health point of view.

Dietary exposure and biomarkers of arsenic in consumers of fish and shellfish from France.

Seafood, especially fish, is considered as a major dietary source of arsenic (As). Seafood consumption is recommended for nutritional properties but contaminant exposure should be considered. The objectives were to assess As intake of frequent French seafood consumers and exposure via biomarkers. Consumptions of 996 high consumers (18 and over) of 4 coastal areas were assessed using a validated food frequency questionnaire. Seafood samples were collected according to a total diet study (TDS) sampling method and analyzed for total As, arsenite (AsIII), arsenate (AsV), arsenobetaïne (AsB), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). The average As dietary exposure is 94.7+/-67.5 microg/kg bw/week in females and 77.3+/-54.6 microg/kg bw/week in males (p<0.001) and the inorganic As dietary exposure is respectively 3.34+/-2.06 microg/kg bw/week and 3.04+/-1.86 microg/kg bw/week (p<0.05). Urine samples were collected from 382 of the subjects. The average urinary As concentration is 94.8+/-250 microg/g creatinine for females and 59.7+/-81.8 microg/g for males (p<0.001). Samples having an As concentration above 75 microg/g creatinine (n=101) were analyzed for inorganic As (As(III), As(V), MMA(V) and DMA(V)) which was 24.6+/-27.9 microg/g creatinine for males and 27.1+/-20.6 microg/g for females. Analyses do not show any correlation between dietary exposure and urinary As. These results show that biological results should be interpreted cautiously. Diet recording seems to be the best way to assess dietary As exposure. Seafood is a high source of As exposure but even among high consumers it is not the main source of toxic As. From a public health point of view these results should be interpreted carefully in the absence of international consensus on the health-based guidance value.

Assessment of dietary exposure of nitrate and nitrite in France.

The aim of this study was to assess the dietary exposure of nitrate and nitrite in France. A total of 13, 657 concentration levels of nitrate and nitrite measured in food, representing 138 and 109 food items, respectively, and coming from French monitoring programmes between 2000 and 2006, were used. Depending on the non-detected and non-quantified analysis treatment, lower and upper concentration mean estimates were calculated for each food item. These were combined with consumption data derived from 1474 adults and 1018 children from the French national individual consumption survey (INCA1), conducted in 1999 and based on a 7-day food record diary. A total of 18% of spinaches, 6% of salads, 10% of cheeses, 8% of meat products and 6% of industrial meat products exceeded the European nitrate maximum level or maximum residual level. A total of 0.4% of industrial meat products and 0.2% of meat products exceeded their European nitrite maximum level or maximum residual level. Nitrate dietary exposure averaged 40% of the acceptable daily intake (ADI; 3.7 mg kg(-1) body weight day(-1)) for adults and 51 - 54% of the ADI for children with the major contributors being, for adults and children, respectively, vegetables (24 and 27% of ADI), potatoes (5 and 11% of ADI), and water (5 and 5% of ADI). The individual nitrate dietary intake of 1.4% (confidence interval (CI(95th)) [0.8; 2.0]) to 1.5% (CI(95th) [0.9; 2.1]) of adults and 7.9% (CI(95th) [6.2; 9.6]) to 8.4% (CI(95th) [6.7; 10.1]) of children were higher than the ADI. Nitrite dietary exposure averaged 33-67% of the ADI (0.06 mg kg(-1) body weight day(-1)) for adults and 67-133% of the ADI for children, with contributions of additive food vectors at 33% of ADI for adults and 50-67% of ADI for children. The individual nitrite dietary intake of 0.7% (CI(95th) [0.3; 1.1]) to 16.4% (CI(95th) [14.5; 18.3]) of adults and 10.5% (CI(95th) [8.6; 12.4]) to 66.2% (CI(95th) [63.3; 69.1]) of children were higher than the ADI.

Dietary exposure to pesticide residues in Yaoundé: the Cameroonian total diet study.

Dietary exposure to pesticide residues was assessed in Yaoundé, Cameroon, using the total diet study (TDS) method. Sixty-three composite samples, representative of the foods as consumed in Yaoundé, were collected, prepared, and analysed for residues of pesticides including organochlorine, organophosphorous, and pyrethroids. A multi-residue method was used with a limit of detection (LOD) of 0.005 mg kg(-1). Additional analyses were performed for dithiocarbamates (LOD=0.050 mg kg(-1)), glyphosate (LOD=0.005 mg kg(-1)) and chlordecone (LOD=0.0008 mg kg(-1)) on certain composites samples. The overall contamination was low with 37 out of 46 pesticides below the LOD in all samples. The estimated upper bound (for values less than the LOD equal the LOD; and values less than the LOQ equal the LOQ) of the mean dietary exposures ranged from 0.24% (cypermethrin) to 3.03% (pirimiphos-methyl) of the acceptable daily intakes (ADIs) for pesticides for which at least one analysis was greater than the LOD. This study suggests a low dietary exposure to pesticide residues in Yaoundé.

Organotin levels in seafood and its implications for health risk in high-seafood consumers.

Fish and fishery products are considered as the main source of organotin compounds (OTC). Unfortunately, little national contamination data is available to assess food exposure of organotins from French consumers. To provide a more accurate estimate of risks to human health, the butyltin, phenyltin and octyltin compounds sampling in four French coastal areas were measured in 159 composite samples (96 fresh and frozen fish, 28 mollusks, 14 crustaceans, 1 echinoderm, 11 canned foods, 4 smoked fish, 5 prepared seafood-based dishes) by capillary gas chromatography coupled with a microwave induced plasma atomic-emission spectrometer (CGC-MIP-AES). In these samples, butyltins were usually predominant and the range of the contamination levels was generally below those of earlier studies (fish: mean 5.6; min-max 1.1-23 microg/kg; fishery products: mean 6; min-max 0.8-14 microg/kg). Fish, especially tuna, salmon, mackerel, saithe/coalfish and cod were largely the main contributors (38%) to the total organotin exposure. With the supplementary contribution of great scallop, surimi, squid and oysters, the exposure exceeded 50% in all. However, the utmost OTC exposure was lesser than 47% of the provisional tolerable weekly intake [EFSA (European Food Safety Agency). Opinion of the Scientific Panel on Contaminants in the food chain on a request from the Commission to assess the health risks to consumers associated with exposure to organotins in foodstuffs. (Question N EFSA-Q-2003-110). The EFSA Journal, 102, 1-119, 2004. http://www.efsa.eu.int]. Nobody would exceed this limit. Finally, as this study has some limitations and since some other sources and health effects have not been clearly evaluated, it appears rational from public health and environmental viewpoints to continue to reduce the OTC levels in the environment.

Dioxins, furans and dioxin-like PCBs: occurrence in food and dietary intake in France.

PCDD/Fs and DL-PCBs contamination data in food products consumed in France collected from national monitoring programmes (2001-04) and representing analytical results for almost 800 individual food samples were combined with food consumption data from the French national dietary survey to estimate PCDD/Fs and DL-PCBs dietary intakes, expressed as toxic equivalents (WHO-TEQs). The mean PCDD/Fs and DL-PCBs intakes were estimated as 1.8 and 2.8 pg WHO-TEQ kg(-1) b.w. day(-1), respectively, for adults (aged 15 years and over) and children (aged 3-14 years). The main contributors to total intake were fish and milk products for both children and adults (48 and 31% for adults and 34 and 43% for children, respectively). DL-PCBs constituted the largest contributor to contamination in most foodstuffs. A life-long intake estimate showed that a non-negligible part of the French population (between 20 and 28%) had an intake above the tolerable monthly intake for dioxins and dioxin-like PCBs of 70 pg WHO-TEQ kg(-1) b.w. month(-1).

Evaluation of certain food additives and contaminants.

This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of various food additives, including flavouring agents, with a view to recommending acceptable daily intakes (ADIs) and to preparing specifications for identity and purity. The Committee also evaluated the risk posed by two food contaminants, with the aim of advising on risk management options for the purpose of public health protection. The first part of the report contains a general discussion of the principles governing the toxicological evaluation and assessment of intake of food additives (in particular flavouring agents) and contaminants. A summary follows of the Committee's evaluations of technical, toxicological and intake data for certain food additives (acidified sodium chlorite, asparaginase from Aspergillus oryzae expressed in Aspergillus oryzae, carrageenan and processed Eucheuma seaweed, cyclotetraglucose and cyclotetraglucose syrup, isoamylase from Pseudomonas amyloderamosa, magnesium sulfate, phospholipase A1 from Fusarium venenatum expressed in Aspergillus oryzae, sodium iron(III) ethylenediaminetetraacetic acid (EDTA) and steviol glycosides); eight groups of related flavouring agents (linear and branched-chain aliphatic, unsaturated, unconjugated alcohols, aldehydes, acids and related esters; aliphatic acyclic and alicyclic terpenoid tertiary alcohols and structurally related substances; simple aliphatic and aromatic sulfides and thiols; aliphatic acyclic dials, trials and related substances; aliphatic acetals; sulfur-containing heterocyclic compounds; aliphatic and aromatic amines and amides; and aliphatic alicyclic linear alpha, beta -unsaturated di- and trienals and related alcohols, acids and esters); and two food contaminants (aflatoxin and ochratoxin A). Specifications for the following food additives were revised: maltol and ethyl maltol, nisin preparation, pectins, polyvinyl alcohol, and sucrose esters of fatty acids. Specifications for the following flavouring agents were revised: maltol and ethyl maltol, maltyl isobutyrate, 3-acetyl-2,5-dimethylfuran and 2,4,5-trimethyl-delta-oxazoline (Nos 1482, 1506 and 1559), and monomenthyl glutarate (No. 1414), as well as the method of assay for the sodium salts of certain flavouring agents. Annexed to the report are tables summarizing the Committee's recommendations for intakes and toxicological evaluations of the food additives and contaminants considered.