dataesr/scientific-paragraphs-categorization huggingface dataset:
, 2016a). In this work, the measured UV spectra were first deconvoluted and then convoluted with a standard triangular slit function with a full width at half maximum of 1 nm and extrapolated using the SHICrivm software package (http://www. rivm. nl/en/Topics/U/UV_ozone_layer_ and_climate/SHICrivm)  (Slaper and Koskela, 1997; Slaper et al. , 1995)  to cover the full UV spectrum as explained in  Heikkilä et al. (2016b). Spectral irradiances are integrated over the UV-B and UV-A. The uncertainties related to the extrapolation are less than 2 and 3 % in the integrated UV-A, for the Jokioinen and Sodankylä Brewers respectively when averaged over daily time window. However, for individual spectra the uncertainties are estimated to be somewhat higher, up to 5-6 % for Sodankylä Brewer with the highest measured wavelength at 325 nm (H.
Slaper, personal communication, 2017). In addition, at both Finnish stations, direct, diffuse and global broadband irradiances are measured every 1 min, with the global irradiance being the sum of the direct and diffuse irradiances on a horizontal plane. These series of data are exploited for selecting cloud-free instants by using the very restrictive algorithm proposed by  Lefèvre et al. (2013). The latter is made of two successive filters. The first one is a constraint on the amount of diffuse irradiance with respect to the global irradiance since the direct irradiance is usually prominent in cloud-free conditions. The second filter analyzes the temporal variability in the global irradiance normalized by the irradiance received at the top of the atmosphere and by a typical air mass since this quantity should be steady for several hours in cloud-free conditions.
, 2013). θ s is given by the SG2 algorithm for the Sun position and angles  (Blanc and Wald, 2012). Ground elevation is extracted from the Shuttle Radar Topography Mission database and has been downloaded from the website http://srtm. csi. cgiar. org/SELECTION/inputCoord. asp. The albedo is the ratio of the upwelling to downwelling flux at the surface and is the integral of the bidirectional reflectance distribution function (BRDF), which depends on the surface-type, its roughness and the wavelength of the impinging radiation. A few institutes provide BRDF products in the UV range or Lambertian equivalent reflectivity (e. g. ,  Herman and Celarier, 1997)  of the Earth's surface with a coarse resolution of 0. 5 or 1 •. In absence of the ideal solution -BRDF parameters in the UV range available worldwide with a grid cell of 0.
The effective UV albedo is part of the version 2 dataset and was derived by comparing measured clear-sky spectra with corresponding radiative transfer model results  (Bernhard et al. , 2007). As a smaller albedo means a smaller contribution to the diffuse part of the irradiance, the difference between the shortwave and effective UV albedo may explain these underestimations seen in Fig. 2a. Results for Sodankylä are shown in Fig. 2b. Cloud-free conditions occur mostly between February and September. The points lie along the identity line with a slight overestimation by the method at low irradiance and an underestimation at large irradiance. R 2 is 0. 98. The bias is low with a value of -0. 5 W m -2 , i. e. , -2 % of the mean value of 20. 8 W m -2. Table  5. Statistical indicators of the performances of the method for UV-A irradiance.
Data availability. UV data from Barrow, Palmer station and Mc-Murdo station were provided by the NSF UV Monitoring Network operated by Biospherical Instruments Inc. and funded by the US National Science Foundation's Office of Polar Programs. Version 2 data used here are available from http://uv. biospherical. com/ Version2/Version2. asp FMI's spectral Brewer UV measurements are available through the European UV Database: http://uv. fmi. fi/uvdb/ www. atmos-meas-tech. net/10/4965/2017/ Atmos. Meas. Tech. , 10, 4965-4978, 2017.
In the absence of a HBGV, a rapid scan of the literature revealed that a dose of 2 mg was considered to be the MLD in several review papers, the initial ones derived from Japan. The Hazardous Substances Data Bank 2  mentions a range of 1-4 mg as the lethal dose. It was noted that a dose of 0. 2 mg was mentioned in some papers as a dose leading to adverse effects but none of the papers mentioned the source of these figures, creating a high level of uncertainty. In a human poisoning case in Spain, following consumption of a sea snail, an intake of 1. 5 mg was estimated based on a suggested intake of 5 g of digestive gland of sea snail containing 300 mg TTX/kg  (Rodriguez et al. , 2008; Fernandez-Ortega et al. , 2010). In addition to TTX, the gland contained 1,000 mg 5,6,11-trideoxyTTX/kg. The patient recovered after artificial respiration.
(Bane et al. , 2014 ; EFSA database, see Section 3. 3. 2 Current occurrence). TTX has a molecular weight of 319. 1 g/M and the formula C 11 H 17 N 3 O 8. TTX is hydrophilic and under acidic conditions, TTX exists as a mixture in equilibrium of the ortho ester, the lactone form,  4-epi-TTX and 4,9-anhydroTTX (Nishikawa and Isobe, 2013). It is stated in several papers (e. g. Bane et al. , 2014; Turner et al. , 2015; FAO/WHO, 2016)  that TTX is heat stable but without reference to the original data. TTX in marine bivalves and gastropods www. efsa. europa. eu/efsajournal.
Food consumption data The EFSA Comprehensive European Food Consumption Database (Comprehensive Database) provides a compilation of existing national information on food consumption at individual level. It was first built in 2010  (EFSA, 2011; Huybrechts et al. , 2011; Merten et al. , 2011). Details on how the Comprehensive Database is used are published in the Guidance of EFSA  (EFSA, 2011)  Within the dietary studies, subjects are classified in different age classes as described in Table  2 ; two additional surveys provided information on specific population groups: 'Pregnant women' (Latvia) and 'Lactating women' (Greece). For acute exposure assessment, and considering the most recent dietary surveys, food consumption data were available from 41 different dietary surveys carried out in 23 different European countries.
A total of 1,677 samples of cockles, mussels, oysters, scallops, razor clams and other water mollusc data on TTX and its analogues were available in the EFSA database. For all of them, analytical results were provided to EFSA for tetrodotoxin (TTX), whereas only 1,135 analytical results were provided for 4-epiTTX, 1,080 for 5,6,11-trideoxyTTX, 1,080 for 11-norTTX-6-ol, 1,080 for mono-deoxyTTX, 1,135 for 4,9-anhydroTTX and 1,080 for 11-oxoTTX. The UK reported analytical results for TTX,  5, 6, mono deoxy TTX, 4,  The LOD and LOQ were never reported for the analogues. With the agreement of the data provider, the LOQ was determined as the minimum of the reported positive values for  5, 6,  In the case of 11-oxoTTX and mono-deoxyTTX, the highest LOQ identified among the other analogues has been used.
The search strategy was designed to identify literature dealing with analytical determination, chemistry, formation, metabolism and toxicity of TTX and also with its occurrence in bivalves and gastropods, effect of processing and exposure to TTX. All search terms and Boolean operators used are presented in detail in Appendix A. The literature search was not restricted to publications in the English language, however, literature in other languages was only considered if an English abstract was available which provided enough details to check the data. The literature search was performed on 11 August 2016 in Web of Science 7  which was identified as an appropriate and exhaustive database for retrieving literature for the present evaluation. The references resulting from the literature search were imported and saved using a software package (EndNote 8  ), which allows effective management of references and citations.
Of the 6,766 retrieved citations duplicate references were removed using the EndNote software. The remaining 2,704 references were screened using title and abstract to identify the relevant literature. Search categories 'neurosciences or physiology' were excluded upfront in the individual subsearches (see Appendix A), as in the pilot search it was seen that papers in this category deal with the use of TTX for investigating the mode and mechanism of action of the blocking of sodium channels and it was decided that such investigations are not of relevance for the present assessment. Upon screening of the abstracts, all papers dealing with chemical features, methods of identification and quantification of TTX and its analogues were considered as potentially relevant. Publications on the occurrence of TTX and its analogues in species covered by the ToR (i.
Methodology for exposure assessment Based on food consumption data from the Comprehensive Database and the TTX occurrence data described in Section 2. 2. 1, TTX acute exposure levels were estimated using a probabilistic approach. Due to the relatively low levels of TTX analogues as compared to TTX and low estimated relative potencies for the detected analogues, the CONTAM Panel decided not to carry out a specific exposure assessment for each of the TTX analogues. Acute exposure was assessed for each reporting day by multiplying the total consumption amount for each food (each type of bivalve, e. g. oysters) by one occurrence level randomly drawn among the individual results available for that type. Respective intakes of the foods consumed that day were then summed and finally divided by the individual's body weight.
This process was iterated 1,000 times for each reporting day. For the calculations, the UB approach was applied. The exposure was modelled using SAS software. In addition, acute exposure was also estimated by using the former 400 g portion and the 95th percentile of actually observed contamination levels on TTX for the different species of water molluscs. Marine gastropods could not be included in the exposure assessment as no occurrence and very few consumption data were available on these species.
Hwang et al. (2005) , citing  Tani (1945) , noted that the MLD 10 of TTX for a human by oral administration is estimated to be 10,000 MU, corresponding to 2 mg based on the observation that the minimum dose that kills a mouse (1 MU) is equal to 0. 2 lg of TTX. Noguchi and Ebesu (2001)  and  Noguchi et al. (2011a,b)  mention the same MLD for humans but without citing a source. Since 50 kg is commonly used as a default bodyweight in the TTX scientific literature, presumably relating to Asian individuals, the amount of 2 mg is sometimes extrapolated to 40 lg/kg bw for these values. The Hazardous Substance Databank (HSDB) 11 notes that 'a fatal dose may be as little as 1-4 mg per person', citing a text book  (Klaasen, 2001)  as the source, which in turn does not provide any information on the basis of this assertion.
Relative potency of TTX analogues Relative potencies (RPs) for TTX analogues, potentially standardised into toxic equivalency factors (TEFs), are required to estimate the total toxicity of a sample based on all analogues identified and quantified. The information available on the relative potencies of TTX analogues is rather scarce but includes the analogues thus far detected in bivalves and gastropods in EU waters (11-norTTX-(6)-ol (S/R), 4-epiTTX, 4,9-anhydroTTX and 5,6,11-deoxyTTX, see Section 1. 2. 3). A partial list can be established based on literature and was recently also presented in a Joint FAO/WHO technical paper (FAO/WHO, 2016) and a corresponding publication  (Botana et al. , 2016)  Data on additional analogues were found in the literature, but some of these were on synthetic analogues, not occurring naturally and are therefore not included.
The data and estimated RPs are presented in Table  9. In most cases, details on the study and interpretation of the results were very limited. It is also evident that the way lethality in mice was presented is rather diverse using parameters like MLD, LD 50 , LD 99 , IC 50 (all in lg/kg bw) or toxic potency (MU/mg compound). In this regard, the CONTAM Panel also noted that the use of the term MLD seems highly variable and confusing. Kao and Fuhrman (1963)  reported MLD, LD 50 and LD 100 values for TTX after i. p. treatment of CF#1 mice of 8, 10 and 12 lg/kg bw, using seven doses and 6-16 animals per dose. This is in agreement with the fact that the MLD is the minimum lethal dose, i. e. the lowest dose that can kill a mouse (see also Section 3. 2. 2 on toxicity). However, Yotsu-Yamashita and colleagues refer to the MLD as being the LD 99 (Yotsu-Yamashita M.
5 lg STX equivalents/kg bw (EFSA CONTAM  Panel, 2009). This was based on the LOAEL in the region of 1. 5 lg STX equivalents/kg bw, derived from the available reports of human poisoning, affecting more than 500 individuals. The Panel noted that many individuals did not suffer adverse reactions at much higher intakes, and therefore, it was expected that this LOAEL was very close to the threshold for effects in the most sensitive individuals. The Panel therefore applied a factor of 3 to the LOAEL in order to estimate a NOAEL of 0. 5 lg STX equivalents/kg bw but no additional factor for variation among humans. The database for STX is much more extensive than that for TTX. The Panel also noted that the difference in toxic potency observed after i. p. vs oral treatment in mice was also rather similar between STX (i.
The first report on findings of TTX and its analogues in bivalves in European waters was by  Turner et al. (2015). TTX and four of its analogues were found in mussels (Mytilus edulis) and Pacific oysters (Crassostrea gigas), harvested from the south coast of England in 2013 and 2014. The results are shown in Table  11. In general, TTX was always found when its analogues were found except in two samples, where 5,6,11-trideoxyTTX was the only finding. TTX and six TTX analogues  5, 6, 4,  were included in the method and quantitation of TTX analogues was conducted assuming the same analytical response factor as TTX. In the absence of standards, an extract from a grey side-gilled sea slug studied by  McNabb et al. (2010)  was used for identification of analogues. Data on the UK samples are included in the EFSA database.
080 mg/kg in the single WF sample analysed. In clam DG, the sum of TTXs was 0. 177 mg/kg. In all 17 samples, 4-epiTTX and 4,9-anhydroTTX were below the LOD. In 2014, samples of mussels were taken during the period April-July from the same water as the previously positive samples and WF were analysed. The concentrations ranged from 0. 025 to 0. 043 mg/kg only for TTX (4-epiTTX and 4,9-anhydroTTX were below the LOD). Also, randomly collected routine samples of shellfish (15 mussels, 1 Venus clam) in June-July 2014 were analysed but no TTXs were found. All the Greek results are shown in Table  11  and the results are also included in the EFSA database. In all the studies, concentrations between LOD and LOQ are quantified and included in the sum of TTXs. Certified TTX together with naturally contaminated samples provided retention times, and these were used for identification of 5,6,11-trideoxyTTX, 5-deoxyTTX, 11-deoxyTTX, 11-norTTX-6(R)-ol and 11-norTTX-6(S)-ol, but none of those analogues were found.
In the Netherlands, the possible presence of TTX and its analogues was investigated in mussels and oysters sampled in 2015 (RIVM-RIKILT, 2015). A total of 152 shellfish samples were analysed, originating from different Dutch production areas. Only in samples collected from certain parts in the Eastern Scheldt estuary, TTX levels exceeded the LOD of 3 lg TTX/kg. Altogether, 55 samples were collected from these areas, namely 12 samples of oysters and 43 samples of mussels. Of these 55 samples, 15 samples had levels of TTX above the LOD, and 11 had concentrations above the LOQ, in this first report being 10 lg/kg. The maximum concentration found was in oysters at a level of 0. 124 mg TTX/kg. These samples are included in the EFSA database which also includes new samples from 2016 which showed concentrations up to a maximum of 0.
Current occurrence data A total of 1,677 samples of marine bivalves analysed for the presence of TTX were available in the final dataset. Most of the available data (n = 1,544 or 92%) were either non-detected or nonquantified values. In case of analogues, altogether only 62 of the total 6,590 reported values (0. 94%) were numerical values. Taking into account that few data were available on analogues combined with relatively low levels and low potencies of the detected analogues, the CONTAM Panel decided not to include them in the exposure assessment. The number of analysed and quantified values for TTX and its analogues are presented in Table  12. In most of the reported samples, the whole flesh of bivalves was analysed. This includes the meat of the animals and their digestive glands. Only Greece reported some results where digestive glands were analysed separately.
Consumption of marine bivalves Since 2008, the CONTAM Panel adopted a series of opinions on the safety of marine biotoxins  (EFSA, 2008a (EFSA, -c, 2009a-e;-e; EFSA CONTAM Panel 2009 , 2010a-d). In all these opinions, in order to assess the exposure, the CONTAM Panel used 400 g as a standard for a large portion of shellfish meat consumed in Europe. This standard amount was first used in 2008, in the scientific opinion on okadaic acid and analogues  (EFSA, 2008b)  and was based on consumption data from five Member States. These food consumption data were derived from dietary surveys from 1985 carried out with different methodologies, including food records (from 2 to 7 days) and food frequency questionnaires. In these studies, the 95th percentiles consumption of shellfish meat ranged from 70 to 465 g, whereas the maximum reported portion sizes ranged from 239 to 1,500 g.
However, the Panel noted that the portion sizes of 1,000 and 1,500 g of shellfish did not likely include only the edible part and could include the shells as well. The estimated 400 g large portion size was then reviewed in 2010 in a statement of the CONTAM Panel, as in the meantime new food consumption data on shellfish were made available to EFSA by different EU countries, mainly within the EFSA Comprehensive Database. In particular, the 95th percentile consumption of shellfish meat ranged from 63 to 251 g in the EFSA Comprehensive Database. This information was not considered sufficient to warrant a revision of the CONTAM Panel's earlier established estimate on the consumption figure of 400 g shellfish meat. The CONTAM Panel based this decision on the uncertainty due to limited information on shellfish consumption in Europe and due to the limited representative data on shellfish types other than mussels.
In addition, an appreciable uncertainty was highlighted in the 95th percentile consumption of shellfish meat from the Comprehensive Database, presenting a wide range of confidence intervals. Since then, the Comprehensive Database has been updated and the current state is that consumption of bivalves was reported in 29 surveys from 17 countries out of the 51 surveys from 23 countries for which food consumption data are available. Number of consumption days, the mean and 95th percentile for consumed quantities are reported in Annex A for water molluscs and for each individual type of bivalves, i. e. mussels, clams, razor clams, oysters and cockles. As suggested in the guidance on the Use of the EFSA Comprehensive European Food Consumption Database in Exposure Assessment (EFSA, 2011a), the 95th percentile has been considered as reliable only when the number of consumption days is at least 60.
Only in the adult group from the surveys of Spain and France, the number of consumption days for bivalves exceeded 300, allowing calculation of the 99th percentile, being 95 and 210 g/day (1. 4 and 3. 8 g/day per kg bw), respectively. Only in 9 out of the 2,102 days the consumption of bivalves reported in the Comprehensive Database exceeded 400 g/day. The CONTAM Panel noted that the consumption data on marine gastropods are limited (32 consumption days in two surveys on whelks and winkles).
Results from current exposure assessment The results of the probabilistic exposure assessment for TTX are presented in detail in Annex B. According to the guidance on the 'Use of the EFSA Comprehensive European Food Consumption Database in Exposure Assessment' the 95th percentile can be considered statistically robust if it is calculated with surveys where the number of consuming days is at least 60 per age group per survey. Similarly, the 99th percentile can be taken into account if the number of consuming days is at least 300. Thus, in the results presented below the calculated mean values are applicable for all the surveys, but the 95th percentiles are calculated for only those where consuming days were at least 60 per age group per survey. Overall, considering consuming days only the average acute exposure level ranged from 0.
Average acute exposure level in the 'toddlers' group ranged from 0. 00 to 0. 02 lg/kg bw. The 95th percentile acute exposure level was not calculated as the surveys were below 60 subjects/consuming days. The highest estimated average exposure level of 0. 09 lg/kg bw occurred in the 'elderly' group. Regarding the different types of water molluscs (see Annex B, worksheet 'Group'), the highest mean exposure level for clams was 0. 02 lg/kg bw, corresponding values for mussels and oysters were 0. 03 and for 0. 09 lg/kg bw, respectively. For razor clams, scallops, cockles and non-specified water molluscs, average acute exposure was 0. The highest 95th percentile exposure, considering only the consumption days, was estimated for oysters (0. 08 lg/kg bw). Acute exposure to TTX was also estimated by multiplying the above mentioned large portion size of 400 g by the 95th percentile of TTX occurrence data and divided by a standard body weight of 70 kg.
Risk characterisation When considering consumption days only, the average acute exposure to TTX ranged from 0. 00 to 0. 09 lg/kg bw, the P95 from 0. 00 to 0. 03 lg/kg bw. It should be noted that only five surveys allowed the estimation of a P95 for one or more age classes or bivalve type, and this did not include the surveys with the highest average intakes where the estimation is based on only few observations. In previous opinions on marine biotoxins, the CONTAM Panel used a large portion size of 400 g. This portion size is higher than the highest P95 observed in food consumption surveys, roughly by a factor of two. Nevertheless, the Panel decided to use this 400 g as a conservative approach. Combining this intake with the P95 of the occurrence data for the whole group of water molluscs, being 28 lg/kg, and assuming a body weight of 70 kg, would result in an intake of 0.
Uncertainty analysis In human case studies, estimated TTX doses are associated with a high level of uncertainty, due to e. g. undefined amounts of actual consumption, the fact that material analysed might not represent what has actually been consumed, and inaccurate concentration estimates of TTX due to the method used or the lack of certified standards. Using the mouse bioassay to determine the TTX content in food consumed or human samples does not enable to discriminate whether indeed TTX or STX caused the effects. There is uncertainty on the MLD of 2 mg per person that is reported in the literature but for which no underlying data could be identified. The use of the term MLD in human, but also in animal studies, is inconsistent throughout the literature. Due to these overall uncertainties, the CONTAM Panel decided not to base the ARfD on results from human case studies.