Using dietary exposure and physiologically based pharmacokinetic/pharmacodynamic modeling in human risk extrapolations for acrylamide toxicity

The discovery of acrylamide (AA) in many common cooked starchy foods has presented significant challenges to toxicologists, food scientists, and national regulatory and public health organizations because of the potential for producing neurotoxicity and cancer. This paper reviews some of the underlying experimental bases for AA toxicity and earlier risk assessments. Then, dietary exposure modeling is used to estimate probable AA intake in the U.S. population, and physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling is used to integrate the findings of rodent neurotoxicity and cancer into estimates of risks from human AA exposure through the diet. The goal of these modeling techniques is to reduce the uncertainty inherent in extrapolating toxicological findings across species and dose by comparing common exposure biomarkers. PBPK/PD modeling estimated population-based lifetime excess cancer risks from average AA consumption in the diet in the range of 1-4 x 10 (-4); however, modeling did not support a link between dietary AA exposure and human neurotoxicity because marginal exposure ratios were 50-300 lower than in rodents. In addition, dietary exposure modeling suggests that because AA is found in so many common foods, even big changes in concentration for single foods or groups of foods would probably have a small impact on overall population-based intake and risk. These results suggest that a more holistic analysis of dietary cancer risks may be appropriate, by which potential risks from AA should be considered in conjunction with other risks and benefits from foods.     

Tea or coffee? A case study on evidence for dietary advice

The present paper explores the level of evidence required to justify giving dietary advice to the public. There are important practical differences between the development of public health nutrition guidelines and guidelines for clinical practice. While the gold standard for evidence for clinical practice guidelines is a meta-analysis of a number of randomised controlled trials, this is often unrealistic and sometimes unethical for the evaluation of public health nutrition interventions. Hence, epidemiological studies make up the bulk of evidence for nutrition guidelines. Tea and coffee are an interesting case study in relation to this issue. They are two of the most commonly consumed beverages worldwide, yet there is little dietary advice on their use. The evidence for a relationship between coffee or tea consumption and several diseases is discussed. The available studies, predominantly epidemiological, together with animal and in vitro studies, indicate that coffee and tea are both safe beverages. However, tea is the healthier option because it has a possible role in the prevention of several cancers and CVD. While the evidence for such relationships is not strong, the public will continue to drink both tea and coffee, and will continue to ask nutritionists to make recommendations. It is therefore argued that advice should be given on the best available data, as waiting for complete data to become available could have severe consequences for public health.     

Chemistry, biochemistry, and safety of acrylamide. A review

Acrylamide (CH2=CH-CONH2), an industrially produced alpha,beta-unsaturated (conjugated) reactive molecule, is used worldwide to synthesize polyacrylamide. Polyacrylamide has found numerous applications as a soil conditioner, in wastewater treatment, in the cosmetic, paper, and textile industries, and in the laboratory as a solid support for the separation of proteins by electrophoresis. Because of the potential of exposure to acrylamide, effects of acrylamide in cells, tissues, animals, and humans have been extensively studied. Reports that acrylamide is present in foods formed during their processing under conditions that also induce the formation of Maillard browning products heightened interest in the chemistry, biochemistry, and safety of this vinyl compound. Because exposure of humans to acrylamide can come from both external sources and the diet, a need exists to develop a better understanding of its formation and distribution in food and its role in human health. To contribute to this effort, this integrated review presents data on the chemistry, analysis, metabolism, pharmacology, and toxicology of acrylamide. Specifically covered are the following aspects: nonfood and food sources; exposure from the environment and the diet; mechanism of formation in food from asparagine and glucose; asparagine-asparaginase relationships; Maillard browning-acrylamide relationships; quenching of protein fluorescence; biological alkylation of amino acids, peptides, proteins, and DNA by acrylamide and its epoxide metabolite glycidamide; risk assessment; neurotoxicity, reproductive toxicity, and carcinogenicity; protection against adverse effects; and possible approaches to reducing levels in food. Further research needs in each of these areas are suggested. Neurotoxicity appears to be the only documented effect of acrylamide in human epidemiological studies; reproductive toxicity, genotoxicity/clastogenicity, and carcinogenicity are potential human health risks on the basis of only animal studies. A better understanding of the chemistry and biology of pure acrylamide in general and its impact in a food matrix in particular can lead to the development of improved food processes to decrease the acrylamide content of the diet.     

Can adverse effects of dietary fat intake be overestimated as a consequence of dietary fat underreporting?

OBJECTIVE: To describe the consequences of systematic reporting bias by the obese for diet-disease relationships. DESIGN: The present report used 24-hour urinary nitrogen and estimates of 24-hour energy expenditure to assess error in diet reporting, and examined the consequence of accounting for this error for associations between dietary fat intake and serum low-density lipoprotein (LDL)-cholesterol. SETTING: Sub-study to the Danish MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) project, carried out in 1987-1988. SUBJECTS: A random sub-sample of the adult Danish male population (n = 152). RESULTS: Correcting dietary fat for underreporting error weakened, rather than strengthened, the association between dietary fat intake and LDL-cholesterol by reducing the slope of the regression from beta = 3.4, P = 0.02 to beta = 2.7, P = 0.04. CONCLUSION: This example illustrates that systematic underreporting of dietary fat by high-risk groups such as the obese may produce an overestimated association. These results imply that previous epidemiological studies showing a positive association between percentage of energy from fat and other health outcomes, e.g. cancer and heart disease, may have overestimated the negative effects of a high-fat diet. If we were able to correctly assess dietary fat intake in general populations, recommendations for fat intake may be more liberal than the 30% suggested today. Improved assessment of fat intake in epidemiological studies is necessary for future development of evidence-based recommendations for diet and health .     

蔬菜中氯氰菊酯残留的风险评估研究

目前使用的绝大多数农药为合成农药,具有急性毒性特征,已开展的慢性评估不能完全符合实际需要,慢性评估结果容易出现过低估计风险,具有急性毒性特征的农药残留必须开展急性评估。为了推进急性评估研究,为我国食品安全监管和残留限量的制定提供技术支持,在WHO原则指导下、基于JMPR建议的方法,开展了蔬菜中氯氰菊酯残留的急性和慢性点评估技术研究。结果显示,济南、青岛和寿光三地市售的西红柿、菜椒、菜豆、茄子、豇豆和芹菜中氯氰菊酯残留摄入是安全的;虽然白菜出现了超标的个例,但99.98%的氯氰菊酯残留摄入不存在危害健康的摄入风险;即使考虑50%的总体误差以及蔬菜占总食物摄入量的比例,至少99.96%的残留摄入不存在危害健康的摄入风险。研究表明,摄入频率高的7类蔬菜中氯氰菊酯残留污染较轻,对消费者（包括孕妇、婴儿和儿童）身体健康危害很小。     

Both food habit change in the past and obesity status may influence the association between dietary factors and postmenopausal breast cancer

OBJECTIVE: Valid dietary data are essential when trying to identify whether or not one or more dietary exposures are responsible for disease. We examined diet composition in women who reported dietary change in the past compared with non-changers, and how the associations between dietary factors and postmenopausal breast cancer are influenced by dietary change, obesity status and misreporting of energy. DESIGN: A population-based prospective cohort study. Data were obtained by a diet history method, anthropometrical measurements and an extensive lifestyle questionnaire including items on past food habit change. SETTING: The Malm? Diet and Cancer (MDC) study, conducted in Malm?, Sweden. SUBJECTS: A subsample of 12,781 women from the MDC cohort recruited from 1991 to 1996. A total of 428 postmenopausal women were diagnosed with incident breast cancer, during 9.2 years of follow-up. RESULTS: Past food habit changers reported healthier food habits and lower energy intake compared with non-changers, a finding that raises issues regarding possible reporting biases. When excluding diet changers, the trend of increased breast cancer risk across omega-6 fatty acid quintiles was stronger, and a tendency of decreased risk emerged for 'fruit, berries and vegetables'. When excluding individuals with non-adequate reports of energy intake, risk estimates were similar to that of the whole sample. In women with body mass index < 27 kg m- 2, significant trends of increased breast cancer risk were seen for total fat and omega-6 fatty acids, and of decreased risk for 'fruit, berries and vegetables'. CONCLUSIONS: This study indicates that both obesity and self-reported past food habit change may be important confounders of diet-breast cancer relationships. The study demonstrates that sensitivity analysis, through stratification, may facilitate interpretation of risk relationships and study results.     

Safety evaluation of an oak-flavored milk powder containing ellagitannins upon oral administration in the rat

Ellagitannins are phenolic compounds that occur in a number of dietary sources such as walnuts, raspberries, pomegranate, strawberries, and oak-aged wines. Ellagitannins have been acknowledged to have antioxidant and cancer chemopreventive activities. However, ellagitannins have also been considered to be "antinutrients" and have been reported to provoke adverse effects in animals. In this context, risk assessment studies are demanded to ensure that chemicals present in food do not compromise food safety. Oak-flavored milk can be obtained by thermal treatment of milk in the presence of oak shavings. The oak-flavored milk can be used to impart wood-like flavor to different recipes. The present study evaluated, under a subchronic approach, the safety of an oak-flavored milk powder containing ellagitannins in rats upon repeated oral administration for 96 days. The effect of 30% oak-flavored milk powder in the diet was evaluated. This amount involved a margin of safety equivalent to the daily intake of 134 yogurts by a 70 kg person for 96 days. Growth rate, food utility index, 9 hematological, and 13 serobiochemical parameters as well as the metabolism and tissue distribution of ellagitannins and derived metabolites were studied. Overall, no significant differences were found in oak-milk-fed rats in any blood parameter analyzed. No effect was found on growth rate and food utility index. Urolithin A was identified in feces of rats fed oak-flavored milk and the glucuronide derivative in urine. No metabolites were found in the liver, kidney, or uterus. Histopathological analysis of liver and kidney corroborated the absence of toxicity. Therefore, these results suggest that the intake of the oak-flavored milk powder assayed in this study is safe and does not involve potential hazard to human health.     

Reduction of acrylamide uptake by dietary proteins in a caco-2 gut model

The report of elevated acrylamide levels in some foods raised an international health alarm, because acrylamide probably has carcinogenic, neurotoxic, and genotoxic properties. However, data on the bioavailability of acrylamide from food matrices in humans are limited. In particular, only little is known about the interactions of acrylamide with food ingredients. Using a human intestine model (Caco-2 cells), this study shows that acrylamide monomers are highly bioavailable and pass the cell monolayer via passive diffusion. Furthermore, acrylamide binds to dietary proteins such as chicken egg albumin under intestinal and cooking conditions. This binding reduces the concentration of acrylamide monomers and leads to a reduced uptake by Caco-2 cells. Hence, it is concluded that a protein-rich diet may reduce acrylamide uptake.     

Review of methods for the reduction of dietary content and toxicity of acrylamide

Potentially toxic acrylamide is largely derived from heat-induced reactions between the amino group of the free amino acid asparagine and carbonyl groups of glucose and fructose in cereals, potatoes, and other plant-derived foods. This overview surveys and consolidates the following dietary aspects of acrylamide: distribution in food originating from different sources; consumption by diverse populations; reduction of the acrylamide content in the diet; and suppression of adverse effects in vivo. Methods to reduce adverse effects of dietary acrylamide include (a) selecting potato, cereal, and other plant varieties for dietary use that contain low levels of the acrylamide precursors, namely, asparagine and glucose; (b) removing precursors before processing; (c) using the enzyme asparaginase to hydrolyze asparagine to aspartic acid; (d) selecting processing conditions (pH, temperature, time, processing and storage atmosphere) that minimize acrylamide formation; (e) adding food ingredients (acidulants, amino acids, antioxidants, nonreducing carbohydrates, chitosan, garlic compounds, protein hydrolysates, proteins, metal salts) that have been reported to prevent acrylamide formation; (f) removing/trapping acrylamide after it is formed with the aid of chromatography, evaporation, polymerization, or reaction with other food ingredients; and (g) reducing in vivo toxicity. Research needs are suggested that may further facilitate reducing the acrylamide burden of the diet. Researchers are challenged to (a) apply the available methods and to minimize the acrylamide content of the diet without adversely affecting the nutritional quality, safety, and sensory attributes, including color and flavor, while maintaining consumer acceptance; and (b) educate commercial and home food processors and the public about available approaches to mitigating undesirable effects of dietary acrylamide.     

Comparative evaluation of cytotoxicity and antioxidative activity of 20 flavonoids

Flavonoids are common dietary components with many health benefits shown through epidemiological studies. However, the fact that flavonoids also act as pro-oxidants and mutagens makes the safety of flavonoids uncertain when used at higher doses. To give a preliminary evaluation on the correlation between beneficial and harmful effects of flavonoids, the antioxidative activity and cytotoxicity of 20 flavonoids from food and herbs were investigated in vitro. The results indicated that luteolin, hydroxygenkwanin, and kaempferol possessed significant dual properties, whereas flavokawain B, flavokawain C, cardamonin, and uvangoletin showed a marked cytotoxicity. The relationships between structure and antioxidant and cytotoxic activity are intensively discussed. In view of the toxicity, the intake of flavonoids in large amounts should not yet be encouraged.     

Estimating Exposure to Methylmercury: Effects of Uncertainties

Uncertainties in exposures can lead to biased estimates of slopes and thresholds in the exposure-response relationships that are developed from regression analysis. This paper reviews published exposure and epidemiological studies of methylmercury (MeHg) from the perspective of the accuracy and precision of the estimates used to represent the actual doses received. Sources of such uncertainties, collectively referred to as “exposure errors”, include instrumental and analytical errors, sampling and survey uncertainties, and individual variability in the relationships between the exposure metrics and the actual doses to target organs. Because the relationship between maternal intake and the consequent dose to the fetal brain varies among individuals, epidemiological studies of the effects of prenatal exposure must necessarily be accompanied by larger exposure uncertainties than comparable studies of effects on the mothers. The increased exposure errors typically result in attenuated slopes of the dose-response functions and under-estimates of thresholds, so that part of the apparent increased sensitivity of the fetus that has been developed from epidemiological studies may in fact be due to their inherently less certain exposures. Sources and magnitudes of exposure error found in the literature are discussed and their statistical ramifications are explored with Monte Carlo simulations. The paper also finds that, after adjusting for exposure error, the relationship between dietary intake and blood concentration is consistent with an average half-life shorter than has typically been used and that using population averages yields a consistent but sub-linear relationship between dietary intake of Hg and hair concentration. Investigators are urged to obtain (and present) data on more than one exposure metric, so that their relative uncertainties may be assessed independently.     

Approach for cancer risk estimation of acrylamide in food on the basis of animal cancer tests and in vivo dosimetry

The question about the contribution from acrylamide (AA) in food to the cancer risk in the general population has not yet had a satisfactory answer. One point of discussion is whether AA constitutes a cancer risk through its genotoxic metabolite, glycidamide (GA), or whether other mechanism(s) could be operating. Using a relative cancer risk model, an improvement of the cancer risk estimate for dietary AA can be obtained by estimation of the genotoxic contribution to the risk. One cornerstone in this model is the in vivo dose of the causative genotoxic agent. This paper presents an evaluation, according to this model, of published AA cancer tests on the basis of in vivo doses of GA in rats exposed in the cancer tests. The present status regarding data with importance for an improved estimation of the contribution from GA to the cancer risk of AA, such as in vivo doses measured in humans, is discussed.     

Potential therapeutic applications of some antinutritional plant secondary metabolites

Plant-based formulations have been used since ancient times as remedial measures against various human and animal ailments. Over the past 20 years interest in traditional medicines has increased considerably in many parts of the world. Whereas modifications in lifestyles, including diet, have had a profound effect on the increased risks of various diseases, there is considerable scientific evidence, both epidemiological and experimental, regarding vegetables and fruits as key features of diets associated with reduced risks of diseases such as cancers and infections. This has led to the use of a number of phytometabolites as anticarcinogenic and cardioprotective agents, promoting a dramatic increase in their consumption as dietary supplements. There are changing perceptions regarding the therapeutic potential of various plant secondary metabolites (PSMs), some of which have also been known to possess certain antinutritional qualities. The knowledge gained at the cellular and molecular levels, and biological activities of PSMs including tannin-polyphenols, saponins, mimosine, flavonoids, terpenoids, and phytates, would be useful in planning for future epidemiological studies and human cancer prevention trials, especially when a large pure dosage is not the option to deliver the active compounds to many tissues. It is well observed that alteration of cell cycle regulatory gene expression is frequently found in tumor tissues or cancer cell lines, and studies have suggested that the herbal-based or plant-originated cell cycle regulators might represent a new set of potential targets for anticancer drugs. The recent upsurge of interest in this area of research and advances made therein indicate that the impact of a number of diseases affecting humans and animals may be lessened, if not prevented, by simple dietary intake of PSMs with putative therapeutic properties.     

Mediterranean diet and cancer

OBJECTIVE: To analyse the role of various aspects of the Mediterranean diet in several common epithelial cancers, including digestive and selected non-digestive tract neoplasms. DESIGN: Systematic analysis of data from a series of case-control studies. SETTING: Northern Italy, between 1983 and 1998. SUBJECTS: Over 12,000 cases of 20 cancer sites and 10,000 controls. RESULTS: For most epithelial cancers, the risk decreased with increasing vegetable and fruit consumption, with relative risk (RR) between 0.3 and 0.7 for the highest versus the lowest tertile. For digestive tract cancers, population-attributable risks for low intake of vegetables and fruit ranged between 15 and 40%. A protective effect was observed also for breast, female genital tract, urinary tract and a few other epithelial neoplasms. A number of antioxidants and other micronutrients showed an inverse relationship with cancer risk, but the main components responsible for the favourable effect of a diet rich in vegetables and fruit remain undefined. Fish tended to be another favourable diet indicator. In contrast, subjects reporting frequent red meat intake showed RRs above unity for several common neoplasms. Intake of whole-grain foods was related to a reduced risk of several types of cancer, particularly of the upper digestive tract. This may be due to a favourable role of fibre, but the issue is still open to discussion. In contrast, refined grain intake and, consequently, glycaemic load and glycaemic index were associated with increased risk of different types of cancer including, among others, breast and colorectal. CONCLUSIONS: A low-risk diet for cancer in the Mediterranean would imply increasing the consumption of fruit and vegetables, as well as avoiding increasing the intakes of meat and refined carbohydrates. Further, olive oil and other unsaturated fats, which are also typical aspects of the Mediterranean diet, should be preferred to saturated ones.     

Influence of soil properties on Ni accumulation in food crops and corresponding dietary health risk with a typical Chinese diet

Nickel (Ni), an essential micronutrient, is toxic to plants and animals at elevated levels. Fewer data are available on the dynamics of Ni than for trace metals such as Cu and Zn. Dietary intake is the major source of Ni, but almost no information is available on dietary intake for Asian populations whose diet contains much less animal products and processed foods than in Western countries. In south‐eastern China, most food is grown on peri‐urban agricultural land and thus, food crops from these areas should be the major source of dietary Ni. A large‐scale survey of Ni in soils and edible crops, including 515 sites and 24 crop species from 10 crop groups, was conducted in Fujian Province, SE China, to assess Ni intake for a typical SE Asian diet. Correlation, principal component analysis (PCA) and data mining were used to identify soil and plant factors that determine Ni accumulation in crops. Both soil Ni content and plant species contributed to Ni accumulation. Crop Ni (Ni_crop) was positively correlated with soil Ni DTPA‐extractible (diethylenetriaminepentaacetic acid) (Ni_DTPA) for many crops. PCA did not identify strong relations between soil‐to‐crop transfer factors and any soil properties. Stepwise linear correlations found positive correlations between Ni_crop and Ni_DTPA; however, relationships between Ni_crop and both silt content and pH varied between crops. Dietary intake of foods containing mean Ni content could lead to health risks, especially for children. It was concluded that sandy soils, rich in organic matter with a large Ni content, are unsuitable for the production of rice and legumes.     

Dietary acrylamide exposure estimates for the United Kingdom and Ireland: comparison between semiprobabilistic and probabilistic exposure models

Since the discovery of acrylamide in foods, there have been many calculations of dietary exposure. Total diet studies have been commonly used to estimate consumer exposure of acrylamide; however, these often fall short in evaluating true exposure levels because of limitations in small occurrence data sets. Dietary exposure to acrylamide can also be estimated by use of modeling packages. The U.K. Food Standards Agency and the Food Safety Authority of Ireland have prepared estimates for dietary acrylamide exposure using semiprobabilistic and probabilistic modeling. Occurrence data were obtained from the European Union acrylamide monitoring database, whereas consumption data were obtained from the relevant U.K. and Irish National Diet and Nutrition Surveys. The mean adult U.K. consumer exposure was estimated as 0.61 microg/kg of body weight (bw)/day and high-level adult consumer exposure (P97.5) as 1.29 microg/kg of bw/day. The mean adult Irish consumer exposure was estimated as 0.59 microg/kg of bw/day and the high-level adult consumer exposure (P97.5) as 1.75 microg/kg of bw/day. Owing to the wide range of acrylamide levels in foods, semiprobabilistic modeling does not always provide an accurate picture of dietary exposure levels and patterns. Therefore, a comparison of semiprobabilistic assessments to probabilistic assessments of U.K. and Irish dietary exposure estimates of certain food groups is provided.     

Sources of variation in nutrient intakes among men in Shanghai, China

BACKGROUND AND OBJECTIVE: Random errors, from any source, will attenuate epidemiological risk estimates. Before we launched the Shanghai Men's Health Study (SMHS), a large population-based cohort study investigating the diet-cancer association among Chinese men, a dietary calibration study was conducted among 96 men aged 40-75 years (mean age 56.5 years), with biweekly 24-hour dietary recalls (24HDRs) implemented over a 1-year period. Data from this study were analysed to evaluate the nature and magnitude of variances for intake of 26 nutrients among SMHS participants, to compare variance ratios of 26 nutrients among Chinese men and women and individuals in other studies, and to estimate the number of 24HDRs required for future dietary calibration studies in similar populations. DESIGN: Ninety-six healthy, free-living men in Shanghai were administered biweekly 24HDR interviews 24 times over a 1-year period. To assess between-individual and within-individual contributions to variance, a mixed effects model was fitted and ratios of within-individual to between-individual (sigma(w)(2)/sigma(b)(2)) dietary intake variances were computed. SETTING: Shanghai, China. RESULTS: In agreement with reports from studies conducted in the USA and many other countries, we found that within-individual variances were usually larger than between-individual variances in dietary intake for all nutrients. The sum of all other variation (e.g. weekday and weekend, seasonal, interviewer) accounted for less than 5% of total variation. Ratios of within- to between-individual variances (for log-transformed data) ranged from 1.25 for carbohydrate intake to near 8 for delta-tocopherol intake. CONCLUSIONS: The results of this study suggest that among middle-aged and elderly Chinese men in Shanghai, within- and between-individual variation account for more than 95% of the total variation for 26 nutrients. Further dietary validation studies in the same population could be adequately carried out with only 12 days of dietary recalls, if 100 participants were enrolled.     

The impact of high non-starch polysaccharide intake on serum micronutrient concentrations in a cohort of women

OBJECTIVE: Many public health campaigns encourage increased fibre consumption, but short-term studies suggest that various components of dietary fibre inhibit the absorption of certain micronutrients including carotenoids. These do not take into account long-term adaptation to nutrient intake levels. We aimed to investigate the effect of non-starch polysaccharide (NSP) fibre on plasma micronutrient concentrations in a large free-living population consuming their usual diet. DESIGN: Prospective cohort study. Semi-weighed 4-day food diaries were analysed for micronutrient and NSP fibre intakes. Blood samples were taken and analysed for carotenoids, vitamin A, vitamin E, thiamine, riboflavin, vitamin B6, vitamin B12, folic acid, vitamin C and trace metals. SETTING: Participants in a large national cohort study who lived within 30 miles of Leeds. SUBJECTS: Two hundred and eighty-three middle-aged women. RESULTS: The association between NSP intake and plasma nutrient concentrations was assessed taking into account nutrient intakes and other dietary and lifestyle factors. Higher levels of NSP were not associated with lower plasma concentrations of the micronutrients measured, even allowing for the higher nutrient levels generally found in high-fibre foods. CONCLUSIONS: Amongst middle-aged women we have shown that current guidelines for increasing the population's NSP consumption can be safely applied. Such guidelines are unlikely to reduce serum micronutrient concentrations, although other, more vulnerable population groups may benefit from further investigation.     

Formation of hemoglobin adducts of acrylamide after its ingestion in rats is dependent on age and sex

The effect of fiber and fat contents of food and of age and sex of animals on the formation of hemoglobin adducts of acrylamide (AA-Hb) in blood has been studied. The results suggest that the absorption of acrylamide (AA) present in food is not affected by the fiber or fat contents of food. However, AA-Hb resulting from the intake of an aqueous solution of AA is dependent on the age and sex of rats: AA-Hb levels were higher in females than in males (3.53- and 2.55-fold higher, respectively, for AA doses of 25 and 100 mg/kg) and in younger than in older rats (30.1% higher in 1.5 month old as compared to 14 month old rats). In males, AA-Hb levels found after the oral administration of AA in an aqueous solution were significantly lower than those found after dietary or intravenous administration. In conclusion, these results show the existence of significant differences in AA bioavailability from an aqueous solution depending on the sex and age of animals. If similar differences also occur in humans, they would be relevant to assess the exposure of different subpopulations to AA.     

Pesticides, selected elements, and other chemicals in infant and toddler total diet samples, October 1978-September 1979

The U.S. Food and Drug Administration (FDA) conducts Total Diet Studies to determine the dietary intake of selected pesticides, industrial chemicals, and elements (including radionuclides). These studies involve the retail purchase and analysis of foods representative of the diets of infants, toddlers, and adults. The individual food items are separated into a number of food groups, each of which is analyzed as a composite. This report summarizes the results for infant and toddler Total Diet samples collected in 10 cities between October 1978 and September 1979. The average concentration, range of concentrations, and calculated average daily intake of the chemicals found are presented by food group. The average daily intakes of the chemicals are similar to those found in the several preceding years and generally are within acceptable limits. The results for samples collected during the same period that represent the adult diet are reported separately.