| 1. |
- Bjermo, Helena, et al.
(författare)
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Lead, mercury, and cadmium in blood and their relation to diet among Swedish adults
- 2013
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915. ; 57, s. 161-9
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to examine the body burden of lead (Pb), mercury (Hg), and cadmium (Cd) in blood among Swedish adults and the association between blood levels, diet and other lifestyle factors. The study was based on a subgroup (n = 273) of the national survey Riksmaten 2010-2011 (4-day food records and questionnaire). Lead, Hg, and Cd were measured in whole blood, and Cd additionally in urine, by mass or fluorescence spectrometry methods. The median values (5-95th percentiles) of the metals in blood were as follows: Pb: 13.4 (5.8-28.6) mu g/L, Hg: 1.13 (0.31-3.45) mu g/L, and Cd: 0.19 (0.09-1.08) mu g/L. All three metals increased with increasing age. Lead levels in blood were positively associated with intakes of game and alcohol, Hg was related to fish intake, and blood Cd related to smoking and low iron stores and to a low meat intake. Body burdens of the studied metals were generally below health based reference values, but several individuals had blood Pb levels above the reference point for possible nephrotoxic and developmental neurotoxic effects. As health effects cannot be excluded, individuals with high Pb exposure should aim at decreasing their body burden, both from food and from other exposure routes. (c) 2013 Elsevier Ltd. All rights reserved.
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| 2. |
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| 3. |
- Hammerling, Ulf, et al.
(författare)
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Identifying Food Consumption Patterns among Young Consumers by Unsupervised and Supervised Multivariate Data Analysis
- 2014
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Ingår i: European Journal of Nutrition & Food Safety. - 2347-5641. ; 4:4, s. 392-403
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Tidskriftsartikel (refereegranskat)abstract
- Although computational multivariate data analysis (MDA) already has been employed in the dietary survey area, the results reported are based mainly on classical exploratory (descriptive) techniques. Therefore, data of a Swedish and a Danish dietary survey on young consumers (4 to 5 years of age) were subjected not only to modern exploratory MDA, but also modern predictive MDA that via supervised learning yielded predictive classification models. The exploratory part, also encompassing Swedish 8 or 11-year old Swedish consumers, included new innovative forms of hierarchical clustering and bi-clustering. This resulted in several interesting multi-dimensional dietary patterns (dietary prototypes), including striking difference between those of the age-matched Danish and Swedish children. The predictive MDA disclosed additional multi-dimensional food consumption relationships. For instance, the consumption patterns associated with each of several key foods like bread, milk, potato and sweetened beverages, were found to differ markedly between the Danish and Swedish consumers. In conclusion, the joint application of modern descriptive and predictive MDA to dietary surveys may enable new levels of diet quality evaluation and perhaps also prototype-based toxicology risk assessment.
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| 4. |
- Herlin, Maria, et al.
(författare)
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Quantitative characterization of changes in bone geometry, mineral density and biomechanical properties in two rat strains with different Ah-receptor structures after long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin
- 2010
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Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 273:1-3, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Both industrial chemicals and environmental pollutants can interfere with bone modeling and remodeling. Recently, detailed toxicological bone studies have been performed following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which exerts most of its toxic effects through the aryl hydrocarbon receptor (AhR). OBJECTIVES: The aims of the present study were to quantitatively evaluate changes in bone geometry, mineral density and biomechanical properties following long-term exposure to TCDD, and to further investigate the role of AhR in TCDD-induced bone alterations. To this end, tissue material used in the study was derived from TCDD-exposed Long-Evans (L-E) and Han/Wistar (H/W) rats, which differ markedly in sensitivity to TCDD-induced toxicity due to a strain difference in AhR structure. METHODS: Ten weeks old female L-E and H/W rats were administered TCDD s.c. once per week for 20 weeks, at doses corresponding to calculated daily doses of 0, 1, 10, 100 and 1000ngTCDD/kgbw (H/W only). Femur, tibia and vertebra from the L-E and H/W rats were analyzed by peripheral quantitative computed tomography (pQCT) and biomechanical testing at multiple sites. Dose-response modeling was performed to establish benchmark doses for the analyzed bone parameters, and to quantify strain sensitivity differences for those parameters, which were affected by TCDD exposure in both rat strains. RESULTS: Bone geometry and bone biomechanical parameters were affected by TCDD exposure, while bone mineral density parameters were less affected. The trabecular area at proximal tibia and the endocortical circumference at tibial diaphysis were the parameters that showed the highest maximal responses. Significant strain differences in response to TCDD treatment were observed, with the L-E rat being the most sensitive strain. For the parameters that were affected in both strains, the differences in sensitivity were quantified, showing the most pronounced (about 49-fold) strain difference for cross-sectional area of proximal tibia. CONCLUSION: The study provides novel information about TCDD-induced bone alterations at doses, which are of relevance from a health risk assessment point of view. In addition, the obtained results provide further support for a distinct role of the AhR in TCDD-induced bone alterations, and suggest that the benchmark dose modeling approach is appropriate for quantitative evaluation of bone toxicity parameters.
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| 5. |
- Sand, Salomon, et al.
(författare)
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Assessment of dietary cadmium exposure in Sweden and population health concern including scenario analysis
- 2012
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Ingår i: Food and Chemical Toxicology. - : Elsevier BV. - 0278-6915 .- 1873-6351. ; 50:3-4, s. 536-544
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Tidskriftsartikel (refereegranskat)abstract
- The median dietary cadmium exposure for adults in Sweden is around 1 mu g/kg/week and the upper 95th and 99th percentiles are 1.6-1.8 and 1.9-2.2 mu g/kg/week, respectively. Potatoes and wheat flour were the most important food categories, contributing with 40-50% to the exposure. Differences in dietary patterns between high and low exposed individuals were observed; for high exposed individuals, seafood and spinach contributed with an exposure similar to that low exposed individuals received from potatoes and wheat flour. Consequences of differences in methodology used for exposure assessment are discussed. The median exposure is a factor 2 lower compared to that estimated by the European Food Safety Authority (EFSA). It is also a factor 1.4 lower compared to that of the assessment used for development of the EFSA tolerable weekly intake (TWI). The potential importance of this latter fact was addressed by adjusting the present assessment to that used for TWI derivation. While the percentage of the population exceeding the TWI was <1% for the present data, it was around 3% for adjusted data, which is more in line with observations at the level of urinary cadmium. Scenario analysis was also performed to addresses the consequence of increasing/decreasing cadmium occurrence levels.
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| 6. |
- Sand, Salomon, et al.
(författare)
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Dose-Related Severity Sequence, and Risk-Based Integration, of Chemically Induced Health Effects
- 2018
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Ingår i: Toxicological Sciences. - : OXFORD UNIV PRESS. - 1096-6080 .- 1096-0929. ; 165:1, s. 74-89
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Tidskriftsartikel (refereegranskat)abstract
- Risk assessment of chemical hazards is typically based on single critical health effects. This work aims to expand the current approach by characterizing the dose-related sequence of the development of multiple (lower- to higher-order) toxicological health effects caused by a chemical. To this end a "reference point profile" is defined as the relation between benchmark doses for considered health effects, and a standardized severity score determined for these effects. For a given dose of a chemical or mixture the probability for exceeding the reference point profile, thereby provoking lower- to higher-order effects, can be assessed. The overall impact at the same dose can also be derived by integrating contributions across all health effects following severity-weighting. In its generalized form the new impact metric relates to the probability of response for the most severe health effects. Reference points (points of departure) corresponding to defined levels of response can also be estimated. The proposed concept, which is evaluated for dioxin-like chemicals, provides an alternative for characterizing the low-dose region below the reference point for a severe effect like cancer. The shape and variability of the reference point profile add new dimensions to risk assessment, which for example extends the characterization of chemical potency, and the concept of acceptable effect sizes for individual health effects. Based on the present data the method shows high stability at low doses/responses, and is also robust to differences in severity categorization of effects. In conclusion, the novel method proposed enables risk-based integration of multiple dose-related health effects. It provides a first step towards a more comprehensive characterization of chemical toxicity, and suggests a potential for improved low-dose risk assessment.
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| 7. |
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| 8. |
- Sand, Salomon
(författare)
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Dose-response modeling : evaluation, application, and development of procedures for benchmark dose analysis in health risk assessment of chemical substances
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, dose-response modeling and procedures for benchmark dose (BMD) analysis in health risk assessment of chemical substances have been investigated. The BMD method has been proposed as an alternative to the NOAEL (no-observedadverse- effect-level) approach in health risk assessment of non-genotoxic agents. According to the BMD concept, a dose-response model is fitted to data and the BMD is defined as the dose causing a predetermined change in response. A lower statistical confidence limit on the BMD (the BMDL) has been suggested as the point of departure in the determination of guidance values such as acceptable daily intakes (ADIs). The fact that the BMD corresponds to an explicit response level has been argued as a major advantage since this introduces consistency and suggests that the point of departure for risk assessment will be based on more information. However, this feature also represents one of the challenges associated with the BMD approach, i.e. which level of response should the BMD correspond to? This and related questions have been addressed in the present thesis. Given the original definition of the BMD as the dose causing a 1 10% increase in the risk for adverse heath effects compared to background, this study has analyzed the impact of model choice in BMD calculations. In the case of quantal data, it is suggested that the BMD is defined as corresponding to risk levels in the range of 5 - 10%. The introduction of the BMD method for continuous endpoints has merited more discussion, and the present thesis has mainly focused on these issues. A probability based procedure suggested for continuous data has been analyzed in detail. By the definition of a cutoff value denoting adverse response, this approach allows the BMD to be interpreted as corresponding to some risk level, similar to the case for quantal data. While this may be of interest, it was shown that the choice of determination of the cut-off point is of high importance and dictates how the BMD depends on the variance. In the present thesis, the BMD approach was introduced for neurobehavioral endpoints using 2,2 ,4,4 ,5-pentabromodiphenyl ether (PBDE99) as a model substance. According to proposed methods of BMD analysis for continuous data, a BMDL of about 0.5 mg/kg bw was obtained for PBDE99. In another application, statistical differences in sensitivity between dioxin sensitive Long-Evans (L-E) and dioxin resistant Han/Wistar (H/W) rats following longterm exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin were demonstrated for the first time. Differences between L-E and H/W rats were most pronounced for volume fraction of hepatic foci; L-E rats were approximately 80 times more sensitive than H/W rats. Considering data on body and organ weights, L-E rats were 10-20 times more sensitive than H/W rats. For retinoid parameters, and hepatic CYP1A1 induction, differences between the strains were generally about 5-fold, and associated with a low uncertainty. Besides analysis and application of suggested procedures for BMD analysis of continuous endpoints, developments have also been proposed. For dose-response relationships that are Sshaped, the BMD may be defined as the dose where the slope of the curve changes the most in the low dose region. It is discussed whether this definition may provide a biological basis for selection of the response associated with the BMD. Considering a conservative scenario, it was shown that the dose where the slope changes the most corresponds to a response in the range of 5 - 10%, if defined as a percentage change in response relative to the magnitude of response. This definition of the BMD may be considered for continuous data in future applications.
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| 9. |
- Schrenk, Dieter, et al.
(författare)
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Risk to human health related to the presence of perfluoroalkyl substances in food.
- 2020
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Ingår i: EFSA journal. European Food Safety Authority. - : Wiley. - 1831-4732. ; 18:9
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Tidskriftsartikel (refereegranskat)abstract
- The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances (PFASs) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Paneldecided to perform the assessment for the sum of four PFASs: PFOA, PFNA, PFHxS and PFOS. These made up half of the lower bound (LB) exposure to those PFASs with available occurrence data, the remaining contribution being primarily from PFASs with short half-lives. Equal potencies were assumed for the four PFASs included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and 'other children' showed a twofold higher exposure. Upper bound exposure was 4- to 49-fold higher than LB levels, but the latter were considered more reliable. 'Fish meat', 'Fruit and fruit products' and 'Eggs and egg products' contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/mL for the sum of the four PFASs in serum was identified for 1-year-old children. Using PBPK modelling, this serum level of 17.5 ng/mL in children was estimated to correspond to long-term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake (TWI) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panelconcluded that parts of the European population exceed this TWI, which is of concern.
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| 10. |
- Suwazono, Yasushi, et al.
(författare)
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Benchmark dose for cadmium-induced osteoporosis in women
- 2010
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Ingår i: Toxicology Letters. - : Elsevier BV. - 1879-3169 .- 0378-4274. ; 197:2, s. 123-127
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Tidskriftsartikel (refereegranskat)abstract
- We applied a hybrid approach to estimate the benchmark dose (BMD) and the lower 95% confidence limit (BMDL) for cadmium-induced bone effects in a population with low environmental exposure. Morning urine samples were collected by 794 Swedish women, aged 53-64 years, participating in a population-based study We measured urinary cadmium (U-Cd), a marker of long-term exposure, and bone mineral density, expressed as its T-score (reference 20-year old women) of the non-dominant wrist. BMD and BMDL, adjusted for relevant covariates. corresponding to an additional risk (BMR) of 5% or 10% were calculated, with the background risk at zero exposure set at 1% or 5%. With a BMR of 5% and a background risk of having low bone mineral density (at U-Cd=0) of 1% or 5% (corresponding to T-score cut-offs -2.75 and -2 09, respectively), the BMD of U-Cd ranged 1 8-3.7 mu g/g creatinine, and the BMDL ranged 1.0-2 1 mu g/g creatinine For a 5% BMR of osteoporosis (T-score < -2 5), the BMD was 29 mu g/g creatinine and the BMDL 1 6 mu g/g creatinine. The lowest obtained BMD of U-Cd for wrist bone mineral density was only slightly higher than the lowest reference concentration previously reported for cadmium-related kidney effects Our results provide additional scientific support for the low tolerably weekly intake (TWI) of cadmium set by the European Food Safety Authority in 2009. (C) 2010 Elsevier Ireland Ltd. All rights reserved
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