Total Cd Intake Research Articles

Health Risk in a Geographic Area of Thailand with Endemic Cadmium Contamination: Focus on Albuminuria.

An increased level of cadmium (Cd) in food crops, especially rice is concerning because rice is a staple food for over half of the world’s population. In some regions, rice contributes to more than 50% of the total Cd intake. Low environmental exposure to Cd has been linked to an increase in albumin excretion to 30 mg/g creatinine, termed albuminuria, and a progressive reduction in the estimated glomerular filtration rate (eGFR) to below 60 mL/min/1.73 m2, termed reduced eGFR. However, research into albuminuria in high exposure conditions is limited. Here, we applied benchmark dose (BMD) analysis to the relevant data recorded for the residents of a Cd contamination area and a low-exposure control area. We normalized the excretion rates of Cd (ECd) and albumin (Ealb) to creatinine clearance (Ccr) as ECd/Ccr and Ealb/Ccr to correct for differences among subjects in the number of surviving nephrons. For the first time, we defined the excretion levels of Cd associated with clinically relevant adverse kidney health outcomes. Ealb/Ccr varied directly with ECd/Ccr (β = 0.239, p < 0.001), and age (β = 0.203, p < 0.001), while normotension was associated with lower Ealb/Ccr (β = −0.106, p = 0.009). ECd/Ccr values between 16.5 and 35.5 ng/L of the filtrate were associated with a 10% prevalence of albuminuria, while the ECd/Ccr value of 59 ng/L of the filtrate was associated with a 10% prevalence of reduced eGFR. Thus, increased albumin excretion and eGFR reduction appeared to occur at low body burdens, and they should form toxicity endpoints suitable for the calculation of health risk due to the Cd contamination of food chains.

Cadmium dietary exposure assessment in the adult population and pre-school children in the Republic of Serbia

Cadmium (Cd) is a toxic metal, present in all matrices of the environment and a common food contaminant. Human exposure to it may elicit many diverse health impairments. The aim of this study was to assess the dietary exposure to Cd for the adult population and preschool children in Serbia using probabilistic methodology. We measured Cd in 11,227 food samples belonging to 50 food items on the Serbian market. Cd was detected in 90% of the tested food items, and in 30.8% of the overall tested samples. The food item that contributed the most to total dietary Cd intake was potatoes (median Cd concentration of 7 ng/g) in adults, and fruit and vegetable juices in children (median Cd concentration of 19 ng/g). Weekly Cd intake shown as 50th and 95th percentiles were 2.54 and 4.74 µg/kg bw in the adult population, and 3.29 and 4.93 µg/kg bw in children. The results of this study are rather preliminary and should be considered as an indication of the need for further, more refined research, which would contribute to a more realistic risk assessment as a high-priority approach, especially in the case of vulnerable subpopulations such as children. Abbreviations: AT SDR: Agency for Toxic Substances and Disease Registry; EEA: European Environment Agency; EFSA: European Food Safety Authority; FAO/WHO: Food and Agriculture Organization/World Health Organization; HI: hazard index; IARC: International Agency for Research on Cancer; JECFA: Joint FAO/WHO Expert Committee on Food Additives; LOD: limit of detection; Cd: cadmium; TWI: tolerable weekly intake; UNEP: United Nations Environment Program; WI: weekly intake

Estimation of cadmium load from soybeans and soy-based foods for vegetarians.

Soybeans, as legumes, belong among food items that contribute most to the dietary intake of the heavy metal cadmium (Cd). The consumption of soy-based foods may contribute significantly to Cd intake in vegetarians as probably the most frequent consumers of these foods. In this research, the weekly dietary intake of Cd from soy-based foods was investigated in 119 participants (including vegetarians, vegans, and non-vegetarians) in the Czech Republic by means of a semi-quantitative food frequency questionnaire (SFFQ) with personal assistance and the measurement of body weight. Cd content in soy-based foods available on the market was determined by means of atomic absorption spectrometry after microwave digestion. Tofu, as the most frequently consumed food item in the vegetarian/vegan group, contributed most to the total dietary Cd intake. It contained 7.6 ± 0.1μg Cd/kg, while the highest Cd content was observed in tempeh (18.1 ± 0.4μg/kg). The highest mean dietary Cd intake per week from soy-based foods was 0.4μg/kg b.w. and was found in the vegan group. The consumption of soy-based foods was the lowest in the non-vegetarian group as was the dietary intake of Cd, which was 0.04μg/kg b.w. per week.

Association between Cadmium Air Exposure and Prostate Cancer Stage at Diagnosis

IntroductionThere is clear evidence that high levels of occupational exposure to cadmium (Cd) lead to a more aggressive prostate cancer (PC) tumor. At levels of exposure which are more relevant to the general population, there is disputing evidence as to whether Cd causes a PC tumor to become more aggressive. In this study, we assess the relationship between ambient exposure to air Cd and PC stage at diagnosis.MethodsWe collected outcome data from the Surveillance, Epidemiology, and End Results (SEER) for reported PC cases diagnosed from 2010 to 2014. PC stage at diagnosis was categorized as metastatic or localized. Exposure data was collected from the 2011 National Air Toxics Assessment (NATA) which was developed by the EPA to review air toxics in the United States. The total exposure concentration of Cd compounds in the air was a county‐level metric calculated by the EPA using weighted averages of air Cd concentration levels measured at various point emission sources. We calculated quintiles of Cd exposure concentration for ease of interpretation. Odds Ratios (OR) and 95% confidence intervals (CI) assessing the relationship between county‐level air Cd exposure and PC stage at diagnosis were calculated using multivariable logistic regression models. Analyses were adjusted for age at diagnosis, sociodemographic status, and overall air quality and were stratified by race.ResultsThe study cohort consisted of 234,991 PC cases from 594 counties reported by SEER. Of these cases, 92.5% were localized and 7.5% metastatic at diagnosis. Higher levels of air Cd exposure were associated with an increased likelihood of a PC case being metastatic at diagnosis. The adjusted odds ratios for the 80th percentile vs 20th percentile of Cd exposure were: all races (OR 1.030, CI 1.019 – 1.040), White (1.049, CI 1.037 – 1.062), Black (1.032, CI 1.0072 – 1.057), and other races (0.965, CI 0.925 – 1.0062).ConclusionHigher Cd air exposure concentration was associated with advanced PC stage at diagnosis with effects that vary somewhat by race. Since inhalation of Cd in the air only contributes to a small percentage of total Cd intake, further studies should be conducted to investigate the effects of other forms of Cd intake such as dietary and water exposures on PC aggressiveness.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Dietary Cadmium Intake and Sources in the US.

Cadmium (Cd) is a toxic heavy metal that can contribute to numerous diseases as well as increased mortality. Diet is the primary source of Cd exposure for most individuals, yet little is known about the foods and food groups that contribute most substantially to dietary Cd intake in the US. Therefore, the objective of this study was to estimate dietary Cd intake and identify major food sources of Cd in the US population and among subgroups of the population. Individuals aged 2 years and older from the National Health and Nutrition Examination Survey (NHANES) 2007–2012 were included in this study (n = 12,523). Cd intakes were estimated from two days of 24-h dietary recalls by matching intake data with the Cd database of the Food and Drug Administration (FDA)’s Total Diet Study 2006 through 2013. The average dietary Cd consumption in the population was 4.63 μg/day, or 0.54 μg/kg body weight/week, which is 22% of the tolerable weekly intake (TWI) of 2.5 μg/kg body weight/week. Greater daily Cd intakes were observed in older adults, males, those with higher income, higher education, or higher body mass index. The highest Cd intakes on a body weight basis were observed in children 10 years and younger (38% of TWI), underweight individuals (38% of TWI), and alcohol non-consumers (24% of TWI). The food groups that contributed most to Cd intake were cereals and bread (34%), leafy vegetables (20%), potatoes (11%), legumes and nuts (7%), and stem/root vegetables (6%). The foods that contributed most to total Cd intake were lettuce (14%), spaghetti (8%), bread (7%), and potatoes (6%). Lettuce was the major Cd source for Caucasians and Blacks, whereas tortillas were the top source for Hispanics, and rice was the top contributor among other ethnic subgroups including Asians. This study provides important information on the dietary Cd exposure of Americans, and identifies the groups with the greatest dietary Cd exposure as well as the major sources of dietary Cd among sociodemographic subgroups.

Toxic metals (Al, Cd, Pb and Hg) in the most consumed edible seaweeds in Europe

Algae are becoming increasingly common because of their importance in vegan and vegetarian diets. Although they are a source of essential minerals, vitamins and antioxidants, these marine organisms have a high absorption capacity that can lead to the accumulation of toxic metals which are dangerous in humans. The objective of this study is to determine the content of toxic metals (Al, Cd, Pb and Hg) in edible seaweed samples marketed in Spain (Europe) to assess the toxicological risk from the intake of these metals. A total of 73 European and Asian algae samples marketed in Tenerife (Canary Islands, Spain) were analyzed by ICP - OES (Inductively Coupled Plasma – Optical Emission Spectrometry) and by CV-AAS (Cold Vapor – Atomic Absorption Spectrophotometry). The major toxic metal was Al, whose highest level was recorded in seaweed salad (57.5 mg Al/kg dry weight). Regarding the origin, the highest concentrations of Al (38.9 mg/kg dw), Cd (0.59 mg/kg dw) and Pb (0.40 mg/kg dw) were found in Asian algae, which may be due to the high levels of industry in the Asian countries. However, the highest concentration of Hg (0.017 mg/kg dw) was found in European algae. The consumption of 5 g of dehydrated seaweed per day represents a percentage of contribution to the tolerable weekly intake of Cd of 22.7%, this percentage may entail a risk when considering total Cd intake. However, the consumption of 5 g a day of dehydrated seaweed would not, pose a risk to the health of adults.

Health Risk Assessment of Dietary Cadmium Intake: Do Current Guidelines Indicate How Much is Safe?

Background:Cadmium (Cd), a food-chain contaminant, is a significant health hazard. The kidney is one of the primary sites of injury after chronic Cd exposure. Kidney-based risk assessment establishes the urinary Cd threshold at 5.24 μg/g creatinine, and tolerable dietary intake of Cd at 62 μg/day per 70-kg person. However, cohort studies show that dietary Cd intake below a threshold limit and that tolerable levels may increase the risk of death from cancer, cardiovascular disease, and Alzheimer’s disease.Objective:We evaluated if the current tolerable dietary Cd intake guideline and urinary Cd threshold limit provide sufficient health protection.Discussion:Staple foods constitute 40–60% of total dietary Cd intake by average consumers. Diets high in shellfish, crustaceans, mollusks, spinach, and offal add to dietary Cd sources. Modeling studies predict the current tolerable dietary intake corresponding to urinary Cd of 0.70–1.85 μg/g creatinine in men and 0.95–3.07 μg/g creatinine in women. Urinary Cd levels of < 1 μg/g creatinine were associated with progressive kidney dysfunction and peripheral vascular disease. A urinary Cd of 0.37 μg/g creatinine was associated with breast cancer, whereas dietary Cd of 16–31.5 μg/day was associated with 25–94% increase in risk of estrogen receptor–positive breast cancer.Conclusion:Modeling shows that dietary intake levels for Cd exceed the levels associated with kidney damage and many other adverse outcomes. Thus, the threshold level of urinary Cd should be re-evaluated. A more restrictive dietary intake guideline would afford enhanced health protection from this pervasive toxic metal.Citation:Satarug S, Vesey DA, Gobe GC. 2017. Health risk assessment of dietary cadmium intake: do current guidelines indicate how much is safe? Environ Health Perspect 125:284–288; http://dx.doi.org/10.1289/EHP108

Human health risk assessment of cadmium via dietary intake by children in Jiangsu Province, China.

The goal of this study was to quantify the exposure to dietary cadmium (Cd) and analyze the major contributors to total Cd intake of children from Jiangsu Province, China. The Cd concentration data were collected by the National Food Contamination Monitoring Program between 2001 and 2009. Consumption data were derived from the Chinese National Nutrition and Health Survey in 2002. The beta-binomial-normal model which included age as a covariate was used to assess the long-term dietary Cd intake assuming lower bound and upper bound concentration scenarios. A tolerable weekly intake of 2.5µg/kg body weight for Cd was applied in the risk assessment. Cd intake decreased as age increased with almost all mean values and P95 of the estimates exceeding the tolerable weekly intake. Children with high-end exposure may suffer non-carcinogenic effects over a lifetime of exposure. Rice and rice products, wheat flour and wheat flour products, crustaceans, pak-choi, pig meat, and beans and bean products were found to be the major contributors to the total Cd intake in children. These conservative estimates of Cd intake indicate possible public health concerns for children in Jiangsu Province.

The landsnail Cepaea nemoralis regulates internal Cd levels when fed on Cd-enriched stinging nettle ( Urtica dioica) leaves at low, field-relevant concentrations

We studied Cd accumulation in Cepaea nemoralis snails at low, but field-relevant Cd concentrations in the diet ( Urtica dioica leaves). Six treatments of U. dioica plants were grown, resulting in leaf Cd concentrations between 0 and 2.6 μg g −1 dw. Seven snails per treatment were fed for 38 days. Leaf Cd concentrations did not affect food consumption rates, and consequently Cd intake rates increased with increasing leaf concentrations. No differences were detected among treatments in the final soft tissue Cd concentrations and body burdens in the snails. Regression analyses showed no positive relationship between either snail Cd concentrations or body burdens and total Cd intake. This suggests a regulation of internal Cd concentrations at low food Cd concentrations. Our data suggest that Cd excretion via the mucus plays a substantial role in this regulation, in addition to Cd excretion via the faeces. Snail shells were no sinks for Cd.

Cadmium dietary intake in the Canary Islands, Spain

Cadmium (Cd) in the human diet constitutes a potential chronic hazard to health. In the nonsmoking general population, diet is the major source of cadmium exposure; therefore, it is important to monitor the dietary intake of this heavy metal to quantify and improve the understanding of Cd accumulation in the human body. The purpose of this study was to determine the levels of Cd in a range of food and drink commonly consumed in the Canary Islands. Food samples (420) were analyzed for Cd by atomic absorption spectrometry. The most recent nutritional survey conducted for the Canarian population was used to define the food and drink groups analyzed. The measured Cd concentrations combined with the food consumption data resulted in a total Cd intake in the Canary Islands of 0.16 μg/kg of body weight/day, which is well below the respective provisional tolerable weekly intake of Cd of 1 μg/kg of body weight per day determined by the FAO/WHO. The results are also compared with values reported for other national and international communities.

Environmental cadmium exposure, adverse effects and preventive measures in Japan

In Japan the most heavily cadmium (Cd)-polluted region is the Jinzu river basin, where Itai-itai disease is endemic and the Kakehashi river basin is the second most polluted region.. The village average Cd concentrations in rice were distributed in the range between 0.02 microg/g and 1.06 microg/g in the Jinzu river basin and 0.11 microg g and 0.67 microg g in the Kakehashi river basin. Severe renal damage has occurred widely in the Jinzu river basin. Even after Cd exposure had ceased, renal dysfunction became worse. Dose-response relationships between Cd exposure and health effects were clearly demonstrated in both regions. The allowable limits (according to the present authors' assessment) of Cd concentrations in rice were estimated to be 0.08 microg g to 0.13 microg g and approximately 2 g for total Cd intake. Renal dysfunction caused by exposure to Cd was associated with an increased mortality in both regions. The increased total Cd intake and high concentration of Cd in rice also exerts an adverse influence on life prognosis.

Comprehensive study of the effects of age, iron deficiency, diabetes mellitus, and cadmium burden on dietary cadmium absorption in cadmium-exposed female Japanese farmers

The absorption rate of dietary cadmium (Cd) was investigated among 38 female farmers who had been exposed to Cd at levels close to the current provisional tolerable weekly intake (PTWI); these levels were much higher than those examined in previous studies. The study group composed of 7 diabetics and their 13 age-matched controls and 6 anemic subjects and their 12 controls. With their informed consent, the study participants were confined in an inn for 7 nights and 8 days to collect all feces and urine and duplicates of all food consumed. The dietary Cd absorption rate was calculated for each subject from her total Cd intake and fecal excretion. The means and 95% confidence intervals (CI) of the diabetic group and the anemic group did not differ significantly from those of their respective controls. By individual analysis using all 38 subjects, however, significant Pearson's correlation coefficients were observed between Cd absorption rate and age, serum ferritin, serum iron, and blood and urine Cd levels. Among these, multiple regression analysis revealed that only age was a significant factor contributing to Cd absorption rate. The actual Cd absorption rate in the youngest age group (20–39 years) was 44.0%, which was highly accelerated compared with the rate in the total subject group of 6.5%, while zero to negative balance was observed in the older subjects. These results demonstrate that age, rather than iron deficiency, diabetes mellitus (DM), or Cd burden, is the only independent factor affecting the Cd absorption rate, suggesting that young women are always at high risk.

Cadmium in blood and urine--impact of sex, age, dietary intake, iron status, and former smoking--association of renal effects.

We studied determinants of cadmium status and kidney function in nonsmoking men and women living on farms in southern Sweden. Median blood Cd (BCd) was 1.8 nmol/L (range, 0.38-18) and median urinary Cd (UCd) was 0.23 nmol/mmol creatinine (range, 0.065-0.99). The intake of Cd per kilogram body weight did not significantly differ between sexes and did not correlate with BCd or UCd, which may be explained by a low and varying bioavailibility of Cd from food items. However, when a subgroup of the study population, couples of never-smoking men and women, were compared, a lower intake per kilogram body weight was found in the women, but the women had a 1.8 times higher BCd and a 1.4 times higher UCd. The higher female BCd and UCd may be explained by higher absorption due to low iron status. BCd and UCd both increased with age and were higher in the ex-smokers, who had stopped smoking more than 5 years before the study, compared to never-smokers. The contribution of locally produced food to the total Cd intake was relatively low and varied. Males living in areas with low soil Cd had lower UCd than the others. However, Cd levels in kidneys from pigs, fed locally produced cereals, did not predict BCd or UCd in humans at the same farms. The kidney function parameter ss2-microglobulin-creatinine clearance was related to UCd, whereas urinary protein-HC, N-acetyl-ss-glucoseaminidase or albumin-creatinine clearance was not when age was accounted for. Hence, even at the low exposure levels in this study population, there was an indication of effect on biochemical markers of renal function.

Association between total cadmium intake calculated from the cadmium concentration in household rice and mortality among inhabitants of the cadmium-polluted Jinzu River basin of Japan

A follow-up survey was conducted to investigate the relationship between total Cd intake and mortality in the Jinzu River basin for 6128 days among 757 inhabitants who ingested household rice. When the subjects were divided into two groups, standardized mortality ratios (SMRs) were 0.94 in men and 1.36 in women for the ≥2.0 g group and 0.68 in men and 0.29 in women for the <2.0 g group (significant in the women). Cox's hazard ratios for men, women, and men+women for the ≥2.0 g group relative to those in the <2.0 g group were 1.406, 3.955 and 1.950 (significant in the men+women). Using total Cd intake as a continuous variable, the hazard ratios were 1.045, 1.146 and 1.049 in men, women, and men+women (significant in the women), respectively. In the Jinzu River basin, increased total Cd intake appears to exert an adverse influence on life prognosis.

Validity of Cadmium Concentration in Rice as the “Dose” of the Dose–Response Relationship between Cadmium Intake and Renal Dysfunction

It is well known that cadmium (Cd) causes renal dysfunction such as increase of β2-microglobulin excretion into urine. Although Cd in rice seems to be one of the largest sources of total Cd intake in Japan, there are very few studies that have epidemiologically clarified the relationship between Cd concentration in rice (Cd-R) and renal dysfunction, because such studies are basically ecological studies, in which confounding factors are difficult to take into consideration. To derive safety levels for foodstuff from Cd-R, it is essential to evaluate the effect of confounding factors. Thus, we investigated the dose–response relationship between renal dysfunction and not only Cd-R but also confounding factors, and we tried to determine whether Cd-R is an adequate indicator of “dose” in the dose–response relationship between Cd intake and renal dysfunction. In 1971, Cd-R data were obtained from rice samples collected by the Environment Agency, Government of Japan in the Fuchu area of Toyama Prefecture, which is known as a place where many itai-itai disease patients were found, and medical data were collected during 1979–1984 by Toyama Prefecture. First, the dose–response relationship between Cd-R and renal dysfunction was analyzed using the data from the Fuchu area. Second, to investigate the effect of confounding factors, analysis using the data from both the Fuchu area and an unpolluted area with environmental factors different from those of the Fuchu area was performed. The results showed that the cause of renal dysfunction could not be explained by Cd-R alone, and confounding factors were not negligible. Although it is difficult to clarify precisely the confounding factors from the available data, it is concluded that deriving a safety level for foodstuffs using only the Cd-R level as a reference is not appropriate.

Cadmium Levels in Feed Components and Kidneys of Growing/Finishing Pigs

Cadmium (Cd) concentrations in pig feeds (one control feed and one feed with reduced nitrogen content), straw, water, and pig kidney cortex were determined in 2 breeds of growing/finishing pigs (n = 96). The total Cd intake from feed was calculated. Feed mixtures and components, straw and kidney cortex samples, and certified reference samples were microwave-digested and analyzed by atomic absorption spectrometry with graphite furnace technique. Total Cd concentration in the control feed was 37.1 micrograms/kg wet weight (w.wt). The highest Cd levels were found in nonlocally produced feed components: vitamin-mineral mixture, lime, dicalcium phosphate, soybean meal, and rapeseed meal. These components contributed 70% of the Cd content in the feed. The main component, barley, which was locally produced, contributed 30% of the total Cd content in feed. The feed with reduced nitrogen content contained less soybean and rapeseed meal and a lower Cd level than the control feed. The Cd levels in kidney cortex varied from 38.0 to 105 micrograms/kg w.wt, with a mean level of 70.9 micrograms/kg. The levels differed between breeds and feeds, but not between gender. There was a significant correlation between Cd level in kidney cortex and age at slaughter, with an increase of 2.8 micrograms/kg w.wt in the kidney for each additional week of survival. The contribution of Cd from nonlocally produced feed components could have environmental effects through application of farmyard manure to local soils.

Background exposure of general women populations in Japan to cadmium in the environment and possible health effects

1. The surveys were conducted in 1990s on 470 non-smoking adult women [with no specific exposure to cadmium (Cd)] in 22 sites in six regions in Japan. 2. It was found that the dietary Cd intake (as a grand geometric mean) was 25.9 μg/day, the Cd level in blood was 2.1 μg/l, and Cd level in urine was 2.1 μg/g creat. 3. Cd in rice contributed about 30% of total dietary Cd intake. 4. There was a substantial reduction in Cd burden when compared with observation in 1980s. 5. Effects on kidney functions were essentially negative when evaluated in terms of β 2-microglobulin (β 2-MG), but might be positive when α 1-microglobulin (α 1-MG) was evaluated; further studies are apparently necessary. 6. No effects on liver functions were detected.

Urban–rural comparison on cadmium exposure among general populations in Shandong Province, China

In 1996, peripheral blood samples and 24-h food duplicate samples together with samples of wheat, rice, foxtail millet and maize were collected from 50 non-smoking women each from Jinan (a provincial capital) and Baiquan (a nearby basically self-sustaining farming village) in China. The samples were analyzed for cadmium (Cd) contents by graphite furnace atomic absorption spectrometry after wet digestion. The dietary Cd intake of the people in the city was 6.4 μg/day as a geometric mean (GM) and 5.9 μg/day for the villagers. The Cd level in blood was 0.48 and 0.29 μg/l (as GMs) for the city and village people, respectively. Thus, Cd burden of the people in the city tended to be greater than that for those in the village. Nevertheless, the Cd burden of the Jinan citizens was lower than the values published for people in large cities in China. When Cd intake via the four cereals was compared with Cd in total food to estimate the total contribution of the four cereals (combined) in total dietary Cd intake, the cereals accounted for 60% of total dietary Cd intake among the city people and as high as 78% among the villagers. Cadmium contents in the four cereals were in a narrow range and it was considered acceptable to combine all cereals in evaluating them as dietary Cd sources.

Accumulation of cadmium from wheat bran, sugar-beet fibre, carrots and cadmium chloride in the liver and kidneys of mice

The gastrointestinal absorption and organ distribution of Cd after exposure for 9 weeks to three fibre-rich foodstuffs (wheat bran, sugar-beet fibre and carrots) were determined in mice. Groups of eight mice were given a diet containing 0.05 mg Cd/kg from wheat bran, sugar-beet fibre, carrots or CdCl2 mixed in a semi-synthetic, low-Cd (< 0.007 mg/kg) feed. A control group was fed on the low-Cd semi-synthetic feed. The water consumption, food consumption and the weight of the animals were monitored throughout the study. The feed was changed once weekly and Cd was analysed in the feed at each change. myo-Inositol phosphates (hexa-, penta-, tetra- and tri-) and Zn, Cu, Fe and Ca were also analysed in the diets. After 9 weeks, the mice were killed and liver and kidneys were sampled and analysed for Cd. The group receiving the wheat-bran diet had significantly lower fractional Cd accumulation (% total Cd intake) in the liver and kidneys than the other groups, indicating a lower fractional absorption of Cd. The wheat-bran diet had markedly higher levels of inositol hexa- and pentaphosphates (phytates) and a Zn level that was twice as high as those in the other diets. The higher levels of myo-inositol hexa- and pentaphosphates in the wheat-bran diet most probably contributed more to the lower fractional absorption of Cd than the elevated Zn level, due to the formation of insoluble Cd-phytate complexes. Compared with the wheat-bran diet, the sugar-beet-fibre and carrot diets contained very low levels of myo-inositol penta- and hexaphosphates, and consequently the fractional Cd absorption from these diets was higher.

Dose-response relationship between total cadmium intake and prevalence of renal dysfunction using general linear models.

To determine the maximum allowable intake limits for chronic dietary exposure to cadmium (Cd), the dose-response relationship between total Cd intake and prevalence of renal dysfunction was examined using general linear models considering the effect of age as a confounder. The target population comprised 1850 Cd-exposed and 294 non-exposed inhabitants of Ishikawa, Japan. They were divided into 96 subgroups by sex, age (four categories) cadmium concentrations in rice (three categories) and length of residence (four categories). As indicators of the cadmium-induced renal dysfunction, glucose, total protein, amino nitrogen, beta 2-microglobulin and metallothionein in urine were employed. General linear models were fitted statistically to the relationship among prevalence of renal dysfunction, sex, age and total Cd intake. Prevalence of abnormal urinary findings other than glucosuria had significant associations with total Cd intake. When total Cd intake corresponding to the mean prevalence of each abnormal urinary finding in the non-exposed subjects was calculated using general linear models, total Cd intakes corresponding to glucosuria, proteinuria, aminoaciduria (men only) and proteinuria with glucosuria were determined to be ca. 2.2-3.8 g and those corresponding to prevalence of metallothioneinuria were calculated as ca. 1.5-2.6 g. The low-molecular-weight protein in urine was confirmed to be a more sensitive indicator of renal dysfunction, and these total Cd intake values were close to those calculated previously by simple regression analysis, suggesting them to be reasonable values as the maximum allowable intake of Cd.