Risk assessment of local dermal effects and skin sensitisation under the EU Chemicals Regulation REACH: a proposal for a qualitative, exposure scenario specific, approach.

Within the framework of REACH, an assessment regarding local dermal effects and skin sensitisation should be performed for substances. Quantitative hazard information for these effects is often not available. Furthermore, it is difficult to relate the way in which animals are exposed in dermal toxicity studies directly to dermal exposure in practice. In the absence of quantitative information, a qualitative assessment for dermal effects is the most reasonable option. The qualitative approach as proposed in the REACH guidance recommends only general risk management measures (RMM) for three categories with a low, moderate and high identified hazard, without specifying which RMM are needed for a specific exposure scenario. We propose to differentiate frequency of exposure based on differences in activities and to compare measured and estimated local skin exposure levels with rules of thumb for evaluation of control of risks per hazard category. For workers, specific RMM regimes are assigned to each combination of hazard category and process category (PROC). For consumers, a strategy in which RMM are arranged from product-integrated measures to the use of personal protective equipment (PPE) is presented. Our approach may be transferred into automated assessment tools like Chesar and CEFIC GES.

Safety of protein hydrolysates, fractions thereof and bioactive peptides in human nutrition.

This paper evaluates the safety for humans with regard to consumption of protein hydrolysates and fractions thereof, including bioactive peptides. The available literature on the safety of protein, protein hydrolysates, fractions thereof and free amino acids on relevant food legislation is reviewed and evaluated. A new concept for the safety assessment of protein hydrolysates and fractions thereof is developed. Benchmarks for the evaluation are safety of total protein intake, safety of free amino acid intake, documented history of safe use, outcome of questionnaires in efficacy studies and safety studies. Similar to the intake of intact proteins with a history of safe use, the intake of hydrolysates made from them, does not raise concern about safety, provided the applied proteolytic enzymes are food grade and thus of suitable quality. The safety of hydrolysates and of fractions thereof, including the so-called bioactive peptides, should always be assessed by the company before market introduction (company safety assessment). Only when a novel protein source is used or a novel production process is applied, which results in significant changes in nutritional value, metabolic effect or increased level of undesirable substances, that products might fall under novel food regulations. This means that company safety assessment should be reviewed and approved by external independent experts (external safety evaluation) and the novel protein hydrolysate (fraction) is authorized by competent authorities before market introduction. It is argued that good judgement on the safety of hydrolysates and the fractions thereof can be obtained by comparing the anticipated intake of amino acids by these products with those levels to be reasonably expected to be ingested under normal conditions of consumption of a balanced and varied diet. The paper shows a decision tree that can be used for safety assessment.

Towards an adequate intake of vitamin D. An advisory report of the Health Council of the Netherlands.

In this report, the Health Council of the Netherlands advises the government on the best policies to achieve an adequate vitamin D supply for the Dutch population. People with a dark skin, those who spend little time outdoors, pregnant and lactating women, veiled women, elderly and children who do not receive vitamin D supplements or infant formula are at risk of vitamin D deficiency. To improve this, more consistent information about vitamin D should be provided. Spending at least 15 min a day outdoors in combination with a healthy diet generates sufficient vitamin D in children and adults with a light skin. All other groups need additional vitamin D from supplements (10-20 microg/day). Fortified foods can only provide part of the additional vitamin D needed.

Toward an optimal use of folic acid: an advisory report of the Health Council of the Netherlands.

In this report, benefits (preventing neural tube defects and folate deficiency), risks (masking vitamin B(12) deficiency), and uncertain effects (risk of colon cancer) of folic acid supplementation and fortification have been weighted. On the basis of the available evidence, the Health Council of the Netherlands advises the Dutch government to improve the use of folic acid approximately at the time of conception by increased education and the implementation of preconception care. It further recommends considering fortifying staple foods, provided that voluntary fortification of specific foods is banned, as otherwise children are at risk of having an excessively high intake of folic acid. Policy making in relation to fortification should take into account all possible health effects, even if the evidence is not strong.

REACH, non-testing approaches and the urgent need for a change in mind set.

The objectives of REACH cannot be achieved under the current risk assessment approach. A change in mind set among all the relevant stakeholders is needed: risk assessment should move away from a labor-intensive and animal-consuming approach to intelligent and pragmatic testing, by combining exposure and hazard data effectively and trying to group chemicals (category approaches). The focus should be on reducing the overall uncertainties of 30,000 chemicals while acknowledging the existence of the uncertainty paradox: reducing uncertainty in the assessment of individual chemicals following the classical chemical-by-chemical approach as we have in previous decades will result in a prolongation of uncertainty for the entire group of 30,000 chemicals as a whole. With the first REACH registration deadline (2010) rapidly approaching, a mind set change is urgently needed. We can speed up the regulatory acceptance process, starting with the maximum use of currently available exposure and hazard data, tools and models. Optimal use should also be made of experimental exposure and hazard data generated under REACH. Only such an approach will make it possible to obtain a sufficient level of information within the time frame of REACH. A much more intensive dialogue between stakeholders is necessary.

Effect of moderate alcohol consumption on adipokines and insulin sensitivity in lean and overweight men: a diet intervention study.

OBJECTIVE: Moderate alcohol consumption is associated with a decreased risk of type II diabetes. This study investigates the effect of moderate alcohol consumption on adipokines and insulin sensitivity. SUBJECTS: Twenty healthy, lean (body mass index (BMI) 18.5-25 kg/m(2); n=11) or overweight (BMI>27 kg/m(2); n=9) men (18-25 years). METHODS: Three cans of beer (40 g alcohol) or alcohol-free beer daily during 3 weeks. RESULTS: Adiponectin and ghrelin concentrations increased (P<0.01) by 11 and 8%, while acylation-stimulating protein (ASP) concentrations decreased by 12% (P=0.04) after moderate alcohol consumption. Concentrations of leptin and resistin remained unchanged. Insulin sensitivity by an oral glucose tolerance test (OGTT) was not affected by moderate alcohol consumption, but 2 h glucose concentrations were lower (P=0.01) after beer (4.5+/-0.1 mmol/l) than alcohol-free beer (4.9+/-0.1 mmol/l). Both free fatty acids and glucagon concentrations showed a stronger increase (P<0.01) after 90 min during OGTT after beer than alcohol-free beer. Changes of adiponectin were positively correlated (r=0.69, P<0.001), and changes of leptin (r=-0.53, P=0.016) and ASP (r=-0.43, P=0.067) were negatively correlated with changes of insulin sensitivity index. All these results did not differ between lean and overweight men. CONCLUSIONS: Moderate alcohol consumption increased adiponectin and ghrelin, while it decreased ASP concentrations both in lean and overweight men. These changes are in line with the hypothesized improvement of insulin sensitivity, but did not affect insulin sensitivity within 3 weeks of moderate alcohol consumption.

Randomized trial of weight-loss-diets for young adults varying in fish and fish oil content.

OBJECTIVE: To investigate the effect of including seafood and fish oils, as part of an energy-restricted diet, on weight loss in young overweight adults. DESIGN: Randomized controlled trial of energy-restricted diet varying in fish and fish oil content was followed for 8 weeks. Subjects were randomized to one of four groups: (1) control (sunflower oil capsules, no seafood); (2) lean fish (3 x 150 g portions of cod/week); (3) fatty fish (3 x 150 g portions of salmon/week); (4) fish oil (DHA/EPA capsules, no seafood). The macronutrient composition of the diets was similar between the groups and the capsule groups, were single-blinded. SUBJECTS: A total of 324 men and women aged 20-40 years, BMI 27.5-32.5 kg/m(2) from Iceland, Spain and Ireland. MEASUREMENTS: Anthropometric data were collected at baseline, midpoint and endpoint. Confounding factors were accounted for, with linear models, for repeated measures with two-way interactions. The most important interactions for weight loss were (diet x energy intake), (gender x diet) and (gender x initial-weight). RESULTS: An average man in the study (95 kg at baseline receiving 1600 kcal/day) was estimated to lose 3.55 kg (95% CI, 3.14-3.97) (1); 4.35 kg (95% CI, 3.94-4.75) (2); 4.50 kg (95% CI, 4.13-4.87) (3) and 4.96 kg (95% CI, 4.53-5.40) on diet (4) in 4 weeks, from baseline to midpoint. The weight-loss from midpoint to endpoint was 0.45 (0.41-0.49) times the observed weight loss from baseline to midpoint. The diets did not differ in their effect on weight loss in women. Changes in measures of body composition were in line with changes in body weight. CONCLUSION: In young, overweight men, the inclusion of either lean or fatty fish, or fish oil as part of an energy-restricted diet resulted in approximately 1 kg more weight loss after 4 weeks, than did a similar diet without seafood or supplement of marine origin. The addition of seafood to a nutritionally balanced energy-restricted diet may boost weight loss.

Effects of sugar intake on body weight: a review.

Weight reduction programmes are mainly focused on reducing intake of fat and sugar. In this review we have evaluated whether the replacement of dietary (added) sugar by low-energy sweeteners or complex carbohydrates contributes to weight reduction. In two experimental studies, no short-term differences in weight loss were observed after use of aspartame as compared to sugar in obese subjects following a controlled energy-restricted diet. However, consumption of aspartame was associated with improved weight maintenance after a year. In two short-term studies in which energy intake was not restricted, substitution of sucrose by artificial sweeteners, investigated mostly in beverages, resulted in lower energy intake and lower body weight. Similarly, two short-term studies, comparing the effect of sucrose and starch on weight loss in obese subjects did not find differences when the total energy intake was equal and reduced. An ad libitum diet with complex carbohydrates resulted in lower energy intake compared to high-sugar diets. In two out of three studies, this was reflected in lower body weight in subjects consuming the complex carbohydrate diet. In conclusion, a limited number of relatively short-term studies suggest that replacing (added) sugar by low-energy sweeteners or by complex carbohydrates in an ad libitum diet might result in lower energy intake and reduced body weight. In the long term, this might be beneficial for weight maintenance. However, the number of studies is small and overall conclusions, in particular for the long term, cannot be drawn.

Alcohol consumption stimulates early steps in reverse cholesterol transport.

Alcohol consumption is associated with increased HDL cholesterol levels, which may indicate stimulated reverse cholesterol transport. The mechanism is, however, not known. The aim of this study was to evaluate the effects of alcohol consumption on the first two steps of the reverse cholesterol pathway: cellular cholesterol efflux and plasma cholesterol esterification. Eleven healthy middle-aged men consumed four glasses (40 g of alcohol) of red wine, beer, spirits (Dutch gin), or carbonated mineral water (control) daily with evening dinner, for 3 weeks, according to a 4 x 4 Latin square design. After 3 weeks of alcohol consumption the plasma ex vivo cholesterol efflux capacity, measured with Fu5AH cells, was raised by 6.2% (P < 0.0001) and did not differ between the alcoholic beverages. Plasma cholesterol esterification was increased by 10.8% after alcohol (P = 0.008). Changes were statistically significant after beer and spirits, but not after red wine consumption (P = 0.16). HDL lipids changed after alcohol consumption; HDL total cholesterol, HDL cholesteryl ester, HDL free cholesterol, HDL phospholipids and plasma apolipoprotein A-I all increased (P < 0.01). In conclusion, alcohol consumption stimulates cellular cholesterol efflux and its esterification in plasma. These effects were mostly independent of the kind of alcoholic beverage

Moderate alcohol consumption and postprandial plasma lipids in men with different risks for coronary heart disease.

BACKGROUND: Moderate alcohol consumption is associated with a reduced coronary heart disease (CHD) risk. Epidemiologic studies have provided conflicting data which suggests that CHD protection may be modulated or may not be modulated by a person's CHD risk profile. METHODS: We examined the effects of moderate alcohol consumption (35 g/day) on postprandial lipoprotein metabolism in two groups of healthy middle-aged men who had different plasma total cholesterol, triglyceride concentrations, and body mass index (BMI), which are three major risk factors for CHD; 11 men had lower plasma lipids and BMI (L-men) and 11 men had higher plasma lipids and BMI (H-men). The effects of alcohol on postprandial lipoprotein metabolism were studied in a crossover design after an acute moderate alcohol intake both after a period of abstinence (alcohol-free beer) and after a period of moderate alcohol consumption (alcohol containing beer). RESULTS: Moderate alcohol consumption changed plasma total cholesterol, total triglycerides, and HDL composition in the postprandial period. Alcohol-induced changes were essentially the same over time in both L-men and H-men. However, changes occurred at a different overall plasma concentration for total cholesterol and total triglycerides. Also, the postprandial response to an acute moderate alcohol dose after a period of abstinence seemed not to essentially differ from the response to an acute moderate alcohol dose after a 4-week period of moderate alcohol consumption. CONCLUSIONS: These results suggest that men who differ in risk for CHD, based on plasma lipids and BMI, but without previous or underlying disease, have a similar postprandial lipid response to a moderate dose of alcohol.

Effects of prebiotics on mineral metabolism.

Nondigestible oligosaccharides (NDOs) have been found to stimulate absorption of several minerals and to improve mineralization of bone. Hence, these substances are potential ingredients for "functional foods." In addition to a nutritional effect, functional foods have physiologic and psychological benefits that result in improved health or reduced risk of chronic disease. Most of the scientific evidence for the functional effects of NDOs is based on animal experiments in which NDOs increased the availability of calcium, magnesium, zinc, and iron. This stimulatory effect of some NDOs is assumed to be mainly due to their prebiotic character. A prebiotic is defined as a substrate or food ingredient that is nondigestible for the host but is fermented selectively by some of the intestinal microflora. Thus, it stimulates the growth and activity of bacteria with beneficial consequences for the host's health. Recently, these findings were confirmed in human studies for some NDOs. The effects seem to be specific for the type of carbohydrate and are likely related to the rate of fermentation by the intestinal flora and appear to depend on the ingested dose. Contradictory results of the effect of prebiotics in literature may be due to the experimental design because the effect of NDOs depends on the dose, the time of administration, the content of calcium in the diet, the part of the skeleton investigated, and the age of the subjects studied.

Moderate alcohol consumption and changes in postprandial lipoproteins of premenopausal and postmenopausal women: a diet-controlled, randomized intervention study.

Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Earlier studies in men have shown that moderate alcohol consumption affects lipoprotein metabolism and hemostasis. In this diet-controlled, randomized, crossover trial, we investigated the effect on lipoprotein metabolism of moderate consumption of red wine or red grape juice with evening dinner for 3 weeks in premenopausal women using oral contraceptives and in postmenopausal women. After 3 weeks, blood samples were collected 1 hour before dinner up to 19 hours after starting dinner at 2-hour or 4-hour intervals. Plasma triglyceride concentrations and very low density lipoprotein (VLDL) triglyceride levels peaked 3 hours after dinner with wine in both premenopausal and postmenopausal women. After wine consumption, the overall high-density lipoprotein (HDL) cholesterol level was increased in postmenopausal women (mean increase 0.17 mmol/L, or 12%, p = 0.03), and the plasma low-density lipoprotein (LDL) cholesterol level was reduced in premenopausal women (mean reduction 0.35 mmol/L, or 12%, p = 0.01) as compared with grape juice consumption. The findings suggest that postprandial lipoprotein metabolism after moderate alcohol consumption differs between oral contraceptive-using premenopausal women and postmenopausal women. The response of postmenopausal women to alcohol resembled the response found in earlier studies in men.

Moderate consumption of beer, red wine and spirits has counteracting effects on plasma antioxidants in middle-aged men.

OBJECTIVE: To evaluate the in vivo effects of moderate consumption of red wine, beer and spirits on antioxidants, antioxidant enzymes and antioxidant capacity. DESIGN: Randomized, diet-controlled, cross-over study. SUBJECTS: Twelve apparently healthy, non-smoking middle-aged men were included; 11 of them completed the study. INTERVENTIONS: Each subject consumed four glasses of red wine, beer, spirits and water (negative control) with evening dinner during four successive periods of 3 weeks, daily at the Institute. The total diet was supplied to the subjects and had essential the same composition during these 12 weeks. RESULTS: Neither the enzyme activities of serum glutathion peroxidase, erythrocyte glutathion reductase and superoxide dismutase nor the plasma concentrations of alpha- and gamma-tocopherol, lutein, zeaxantin, beta-cryptoxanthin, lycopene and alpha-carotene were affected. Plasma beta-carotene concentrations were decreased after 3 weeks' consumption of red wine, beer and spirits (40 g alcohol/day) as compared to consumption of water, by 15% (P=0.0005), 11% (P=0.010) and 13% (P=0.003), respectively. Also, plasma ascorbic acid was decreased after beer (15%, P=0.004) and spirits (12%, P=0.030), but not after wine consumption. Serum uric acid concentrations were increased after consumption of beer (15%, P<0.0001), spirits (8%, P=0.008) and red wine (9%, P=0.003). The overall serum antioxidant capacity, assessed as Trolox equivalent antioxidant capacity (TEAC), was similar for all treatments. CONCLUSIONS: Moderate consumption of red wine, beer and spirits has counteracting effects on plasma antioxidant components, resulting in no significant effect on overall antioxidant status. The effects on antioxidant parameters are largely independent of the type of alcoholic beverage, and probably irrelevant to chronic disease risk. SPONSORSHIP: Dutch Foundation for Alcohol Research (SAR).

The protein digestibility-corrected amino acid score.

The protein digestibility-corrected amino acid score (PDCAAS) has been adopted by FAO/WHO as the preferred method for the measurement of the protein value in human nutrition. The method is based on comparison of the concentration of the first limiting essential amino acid in the test protein with the concentration of that amino acid in a reference (scoring) pattern. This scoring pattern is derived from the essential amino acid requirements of the preschool-age child. The chemical score obtained in this way is corrected for true fecal digestibility of the test protein. PDCAAS values higher than 100% are not accepted as such but are truncated to 100%. Although the principle of the PDCAAS method has been widely accepted, critical questions have been raised in the scientific community about a number of issues. These questions relate to 1) the validity of the preschool-age child amino acid requirement values, 2) the validity of correction for fecal instead of ileal digestibility and 3) the truncation of PDCAAS values to 100%. At the time of the adoption of the PDCAAS method, only a few studies had been performed on the amino acid requirements of the preschool-age child, and there is still a need for validation of the scoring pattern. Also, the scoring pattern does not include conditionally indispensable amino acids. These amino acids also contribute to the nutrition value of a protein. There is strong evidence that ileal, and not fecal, digestibility is the right parameter for correction of the amino acid score. The use of fecal digestibility overestimates the nutritional value of a protein, because amino acid nitrogen entering the colon is lost for protein synthesis in the body and is, at least in part, excreted in urine as ammonia. The truncation of PDCAAS values to 100% can be defended only for the limited number of situations in which the protein is to be used as the sole source of protein in the diet. For evaluation of the nutritional significance of proteins as part of mixed diets, the truncated value should not be used. In those cases, a more detailed evaluation of the contribution of the protein to the amino acid composition of the mixed diet is required. From such an evaluation, it appears that milk proteins are superior to plant proteins in cereal-based diets.

Determinants of bone mass and bone geometry in adolescent and young adult women.

Bone mass and bone geometry are considered to have independent effects on bone strength. The purpose of this study was to obtain data on bone mass and geometry in young female populations and how they are influenced by body size and lifestyle factors. In a cross-sectional, observational study in six European countries, 1116 healthy Caucasian girls aged 11-15 and 526 women aged 20-23 participated. Their radius was scanned at the ultradistal site and at a site approximately 30% of the radius length from the distal end with dual energy X-ray absorptiometry (DXA). The following parameters were assessed from the scans: bone mineral content (BMC), bone mineral density (BMD), cortical wall thickness (CWT), middistal diameter (D), cortical index (CI = 2CWT/D), and the Breaking Bending Resistance Index (BBRI = (D4 - [D-CWT]4)/D). Calcium intake was assessed by 3-day food records and physical activity by questionnaire. Body size parameters were measured by anthropometry. All parameters showed an increasing trend with pubertal stage and age, except for physical activity and calcium intake. BMC and BMD were relatively more dependent on body weight and age at menarche, whereas variation in D and the mechanical index BBRI was better explained by differences in height and grip strength. CI and CWT were relatively independent of variation in body size, whereas BMC and BBRI especially were explained for a substantial proportion (25-33% in the young adults) by body size parameters. Dietary intake of calcium and level of physical activity seem to contribute little to variation in bone parameters.

Daily moderate alcohol consumption increases serum paraoxonase activity; a diet-controlled, randomised intervention study in middle-aged men.

Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Part of this inverse association may be explained by its effects on HDL. Paraoxonase, an HDL-associated enzyme, has been suggested to protect against LDL oxidation. We examined the effects of moderate consumption of red wine, beer and spirits in comparison with mineral water on paraoxonase activity in serum. In this diet-controlled, randomised, cross-over study 11 healthy middle-aged men consumed each of the beverages with evening dinner for 3 weeks. At the end of each 3 week period, blood samples were collected pre- and postprandially and after an overnight fast. Fasting paraoxonase activity was higher after intake of wine (P<0. 001), beer (P<0.001), and spirits (P<0.001) than after water consumption (149.4+/-111.1, 152.6+/-113.1, 152.8+/-116.5 and 143. 1+/-107.9 U/l serum), but did not differ significantly between the 3 alcoholic beverages. Similar effects were observed pre- and postprandially. The increases in paraoxonase activity were strongly correlated with coincident increases in concentrations of HDL-C and apo A-I (r=0.60, P<0.05 and r=0.70, P<0.05). These data suggest that increased serum paraoxonase may be one of the biological mechanisms underlying the reduced coronary heart disease risk in moderate alcohol consumers

Lactulose stimulates calcium absorption in postmenopausal women.

Animal studies have indicated that calcium absorption is increased by lactulose, a synthetic disaccharide. Therefore, the influence of lactulose on calcium absorption was measured in postmenopausal women who may benefit from the possible enhancing effect of lactulose on calcium absorption. Twelve postmenopausal women drank 100 ml of water containing 5 or 10 g of lactulose or a reference substance at breakfast for 9 days. The three treatments were given according to a randomized, double-blind, cross-over design, separated by two 19-day wash-out periods. On the 8th day of each treatment period, 44Ca dissolved in orange juice was drunk immediately after the solution with the study substance and just before a standard breakfast with 162 mg of carrier calcium. Within half an hour, 48Ca was given intravenously. Based on isotope ratios measured in urine collected before and until 36 h after isotope administration, true fractional calcium absorption was calculated. Calcium absorption during the treatments with the reference substance, 5 g and 10 g of lactulose was (mean +/- SD) 27.7 +/- 7.7, 30.0 +/- 7.6, and 32.2 +/- 7.0, respectively. A significant difference in calcium absorption was found between the highest dose of lactulose and the reference treatment (p < 0.01). A significant linear trend was found between the dose of lactulose and its positive effect on calcium absorption. In conclusion, in postmenopausal women a 9-day consumption of lactulose increases calcium absorption in a dose-response way. More research is warranted to explore how lactulose stimulates calcium absorption and whether it is able to improve calcium balance and/or to attenuate the rate of aging bone loss.