Distributions for time, interspecies and intraspecies extrapolation for deriving occupational exposure limits.

This work aimed at improving the empirical database of time (i.e., exposure duration), interspecies and intraspecies extrapolation when deriving occupational exposure limits (OELs). For each extrapolation step, a distribution was derived, which can be used to model the associated uncertainties. For time and interspecies extrapolation, distributions of ratios of dose descriptors were derived from studies of different length or species. National Toxicology Program (NTP) study data were manually assessed, and data from REACH (Registration, Evaluation and Authorisation of Chemicals) registration dossiers were evaluated semi-automatically. Intraspecies extrapolation was investigated by compiling published studies on human toxicokinetic and toxicodynamic variability. A new database was established for toxicokinetic differences in interindividual susceptibility, including many inhalation studies. Using NTP data produced more reliable results than using REACH data. The geometric mean (GM) for time extrapolation subacute/chronic agreed with previous evaluations (GM = 4.11), whereas the GM for subchronic/chronic extrapolation was slightly higher (GM = 2.93) than the GMs found by others. No significant differences were observed between systemically and locally acting substances. Observed interspecies differences confirmed the suitability of allometric scaling, with the derived distribution describing remaining uncertainty. Distributions of intraspecies variability at the 1% and 5% incidence level had medians of 7.25 and 3.56, respectively. When compared with assessment factors (AFs) currently used in the EU, probabilities that these AFs are protective enough span a wide range from 10% to 95%, depending on the extrapolation step. These results help to select AFs in a transparent and informed way and, by allowing to compare protection levels achieved, to harmonise methods for deriving OELs.

Derivation of occupational exposure limits: Differences in methods and protection levels.

Frameworks for deriving occupational exposure limits (OELs) and OEL-analogue values (such as derived-no-effect levels [DNELs]) in various regulatory areas in the EU and at national level in Germany were analysed. Reasons for differences between frameworks and possible means of improving transparency and harmonisation were identified. Differences between assessment factors used for deriving exposure limits proved to be one important reason for diverging numerical values. Distributions for exposure time, interspecies and intraspecies extrapolation were combined by probabilistic methods and compared with default values of assessment factors used in the various OEL frameworks in order to investigate protection levels. In a subchronic inhalation study showing local effects in the respiratory tract, the probability that assessment factors were sufficiently high to protect 99% and 95% of the target population (workers) from adverse effects varied considerably from 9% to 71% and 17% to 87%, respectively, between the frameworks. All steps of the derivation process, including the uncertainty associated with the point of departure (POD), were further analysed with two examples of full probabilistic assessments. It is proposed that benchmark modelling should be the method of choice for deriving PODs and that all OEL frameworks should provide detailed guidance documents and clearly define their protection goals by stating the proportion of the exposed population the OEL aims to cover and the probability with which they intend to provide protection from adverse effects. Harmonisation can be achieved by agreeing on the way to perform the methodological steps for deriving OELs and on common protection goals.

Nutrient Adequacy and Associated Factors in a Nationwide Sample of German Toddlers.

OBJECTIVES: Nutrition in toddlerhood may have short- and long-term impacts on health and nutrition behavior. The objectives of the present article are to describe intake of energy and nutrients from the end of infancy to toddlerhood, and to examine dietary and socioeconomic factors (socioeconomic status [SES]) associated with total nutrient adequacy measured by a nutrient-based index (Nutrient Quality Index [NQI]). METHODS: In the German Representative Study of Toddler Alimentation from 2008, 7-day estimated dietary records were collected cross-sectionally from toddlers ages 10 to 36 months (n = 525). The study population was recruited in the TNS access panel. The intakes of energy and 18 nutrients were evaluated and the NQI was determined. Age trends in nutrient intake were tested with analysis of variance. Analysis of the association between SES and the NQI was performed by multiple linear regression analysis. RESULTS: In all of the age groups, energy intake was close to the reference value representing moderate physical activity. The mean intake of most vitamins and minerals reached the respective reference values, but nutrient density decreased with age. Dietary intakes of iron, iodine, and vitamin D are low in our study. The NQI reached approximately 80 points and was lower in older children than in younger children. NQI was not affected by SES but by formula use. CONCLUSIONS: Nutritional quality measured by total nutrient intake is altogether high in German toddlers, although NQI decreased with increasing age. The NQI is independent of social class. The positive association with formula intake can be explained by the general enrichment of vitamins and minerals of these products.

Anthocyanins in the diet of children and adolescents: intake, sources and trends.

PURPOSE: Anthocyanin intake estimations in large cohorts include almost exclusively adults. For the purpose of early dietary prevention, however, it is of great interest to estimate anthocyanin intake of children and adolescents. METHODS: Anthocyanidin content values from the USDA Database (excluding the values for bananas and nuts) were assigned to foods consumed by 4-18-year-old participants of the DONALD Study. Between 1990 and 2009, 920 participants provided 6,707 3-day weighed dietary records. Intake of anthocyanins (expressed as their aglycones anthocyanidins) and their food sources were determined. For investigating age and time trends in anthocyanidin density (mg/MJ), a polynomial mixed regression model was built. RESULTS: We found the estimated median anthocyanidin intake to be around 6 mg/day, strawberries representing the main source. Anthocyanidin density of the diet was about 0.2 mg/MJ higher in girls than in boys, decreased with age, decreased over time in the first half of the study period and increased over time thereafter. CONCLUSIONS: Anthocyanin intake in the young is characterised by differences in anthocyanidin density of the diet between girls and boys and by decreasing density from young childhood to adolescence. Observations in this German study population should be extended by further studies in other countries.

Relative validity of a 3 d estimated food record in German toddlers.

OBJECTIVE: To determine the relative validity of a 3 d estimated food record (EFR) used to assess energy and nutrient intakes in toddlers, using a 3 d weighed food record (WDR) as the reference method. DESIGN: Parents reported the food and beverage intakes of their children using an EFR concurrently with a WDR over three consecutive days. Estimation of mean differences, Spearman correlation coefficients, cross-classifications and Bland-Altman plots were used to assess the agreement between the intakes of energy and fourteen nutrients obtained from the EFR and the WDR. SETTING: Data obtained from a representative sample of infants or toddlers in Germany. SUBJECTS: Sixty-seven toddlers aged 10-36 months who had completed an EFR for a 3 d recording period that corresponded to the WDR were included in the present analysis. RESULTS: Energy and nutrient intakes did not differ between the EFR and the WDR, except for linoleic acid and retinol. For all dietary intakes, Spearman rank correlation coefficients between the EFR and the WDR ranged from 0·35 to 0·80 (P ≤ 0·004). The proportion of participants correctly classified into quartiles ranged from 75 % for ascorbic acid intake to 96 % for Fe intake, and the percentage of misclassification was 9 % or less. The weighed κ values ranking the participants ranged from 0·23 for ascorbic acid intake to 0·59 for Fe intake. The Bland-Altman plots indicated a good agreement for all dietary intakes estimated from the EFR. CONCLUSIONS: Our study suggests that this EFR is a valid assessment instrument for estimating the energy and nutrient intakes among toddlers at the group level.

Liking of anthocyanin-rich juices by children and adolescents.

There is evidence that a diet rich in plant foods is protective against cardiovascular disease and cancer, partly attributable to secondary plant metabolites such as anthocyanins, a colourful group of flavonoids. As at present children and adolescents do not consume the recommended amounts of fruits and vegetables, one possible way of increasing intake, and particularly intake of anthocyanins, may be an anthocyanin-rich juice, since fruit juice is popular with young Germans. We produced eight different fruit products (six juices, two smoothies), and conducted hedonic tests with participants from the DONALD Study. Paired comparisons showed that most subjects preferred apple to apple-bilberry juice, but grape vs. grape-bilberry juice was liked equally frequently. Rated on a hedonic scale the grape-bilberry mixture was preferred to apple-bilberry, both as juice and as smoothie. With regard to viscosity, juices were preferred to smoothies, both as grape-bilberry and as apple-bilberry. Internal Preference Mapping revealed however consumer subgroups with different preferences, raising the question which product should be promoted in order to reach a large target group. The product richest in anthocyanins, grape-bilberry juice, was accepted very well and may therefore be suitable for promotion to children, although the high sugar content of this juice must be taken into account.

Anthocyanins in the diet of infants and toddlers: intake, sources and trends.

PURPOSE: Anthocyanins, a colourful group of flavonoids in many fruits and vegetables, are proposed to provide positive impact on human health. However, intake estimations have almost exclusively been conducted in adult populations. As infants and toddlers are a promising age group for health promotion, we examined their anthocyanin intake (as anthocyanidins), food sources and trends of age and time in anthocyanidin density. METHODS: Anthocyanidin content values from the USDA Database were assigned to foods consumed in 4,617 3-day weighed dietary records from 1990 to 2009 by 942 3-36-month-old subjects of the DONALD Study. As we assume that anthocyanidins found in bananas do not originate from anthocyanins, the anthocyanidin value for bananas was excluded from our analysis. To investigate age and time trends in anthocyanidin density, polynomial mixed regression models were used. RESULTS: Median anthocyanidin intake was zero in young infants and around 4 mg/day in older infants and toddlers, strawberries and pomaceous fruit representing the main sources. Anthocyanidin density increased from 6 to 18 months of age, followed by a slight decrease till 36 months of age. During the 20-year study period, a decrease in density in infants was observed, but a slight increase in toddlers. CONCLUSIONS: Anthocyanidin density in the diet seems to increase notably from infancy to toddlerhood and to have decreased in the youngest over the last 20 years. These first observations in a German population of infants and toddlers need to be extended by further studies examining anthocyanin intake in these age groups in other countries.

Dietary intake and plasma concentrations of PUFA and LC-PUFA in breastfed and formula fed infants under real-life conditions.

BACKGROUND: The breastfed infant is usually used as standard for formula feeding, also regarding long-chain polyunsaturated fatty acids (LC-PUFA). Here, plasma fatty acid concentrations in formula fed infants and the effects of LC-PUFA supplementation were investigated under real-life conditions. METHOD: Term healthy infants being fully milk fed until the age of 4 months were categorized as breast milk "BM" (n = 73) if consuming >95% of energy from breast milk or formula (F) if consuming >95% of energy from formula subdivided into formula without (F-) (n = 15) and with LC-PUFA supplementation (F+) (n = 15). Formula as marketed was chosen by the parents. Dietary fatty acids (FA) intake was calculated from continuous dietary records from 2 months of age onwards. Total plasma FA were analyzed at the age of 4 months with docosahexaenoic acid (DHA) as primary outcome. RESULTS: Dietary ratios of the polyunsaturated fatty acids (PUFA; linoleic acid/alpha-linolenic acid) were smaller in both F groups than in the BM group. Plasma DHA as % of total FA was similar in BM and F(+) but higher in BM in absolute amounts (mg/L). Plasma DHA as % of total FA in F(-) was higher than what might be supposed on the basis of dietary intake. CONCLUSION: Infants consuming present-day LC-PUFA-supplemented formula achieved plasma LC-PUFA concentrations similar to breastfed infants. In infants consuming non-LC-PUFA-supplemented formula, the favorable PUFA pattern of the formula may have supported n-3 LC-PUFA biosynthesis.