Estimation of the dietary intake of cadmium, lead, mercury, and arsenic by the population of Santiago (Chile) using a Total Diet Study.

Dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) by the population of Santiago (Chile) was determined using a Total Diet Study in the market basket modality. After conducting a survey of the foods consumed in the last 24 h, the most consumed food products were included in the basket. Subsequently, they were cooked or prepared according to typical Chilean procedures and grouped into 17 food categories according to their chemical characteristics. The fish and shellfish group had the highest contents of As (1351 ng/g wet weight, ww), Cd (277 ng/g ww), and Hg (48 ng/g ww), while the sugar group had the highest content of Pb (251 ng/g ww). For a person with a body weight of 68 kg, the dietary intakes of As (77 microg/day), Cd (20 microg/day), Hg (5 microg/day), and Pb (206 microg/day) are lower than the provisional tolerable weekly intake values established by the FAO/WHO. Consequently, the total intakes of As, Cd, Hg, and Pb in Santiago (Chile) are within the limits estimated as safe.     

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 microg/day, the Cd level in blood was 2.1 microg/l, and Cd level in urine was 2.1 microg/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 beta2-microglobulin (beta2-MG), but might be positive when alpha1-microglobulin (alpha1-MG) was evaluated; further studies are apparently necessary. 6. No effects on liver functions were detected.     

Cause-specific mortality and cancer incidence rates in relation to urinary beta2-microglobulin: 23-year follow-up study in a cadmium-polluted area

A longitudinal study was performed to investigate the associations of exposure to environmental cadmium (Cd) with cause-specific mortality and cancer incidence rates. The study population comprised 275 adults living in a Cd-polluted area, Nagasaki Prefecture, Japan. The follow-up period extended from 1982 to 2005 for the analysis of cancer mortality, and from 1985 to 2002 for the analysis of cancer incidence. In the study area, the daily Cd intake from foods had decreased after 1980-1983 because of the restoration of Cd-polluted rice fields. The mortality rate among those with urinary beta2-microglobulin (U-beta2M)>/=1000 microg/g creatinine was significantly higher than that of the Japanese population for death from causes other than cancer, but not for cancers (177 at the 95% confidence interval [CI] 94-303). From analysis within the Cd-polluted area, the age-adjusted rate ratio of cancer deaths associated with increased U-beta2M was 2.58 (95% CI 1.25-5.36). The incidence rate of cancer among those with U-beta2M>/=1000 microg/g creatinine was 1.38 (95% CI 0.69-2.47) times that of the regional reference rate. Within the Cd-polluted area, the age-adjusted rate ratio of developing cancer associated with high U-beta2M was 1.79 (95% CI 0.84-3.82). In summary, there was a significant association between U-beta2M excretion and cancer mortality. However, there was neither a significantly increased standardized incidence ratio of cancer, nor significant relationship between U-beta2M and cancer incidence rate, though the point estimates were higher than unity. Continued follow-up and investigation of a larger cohort may be required before drawing a conclusion for the association between exposure to environmental Cd and cancer risk.     

Effect of smoking on cadmium and lead concentrations in human amniotic fluid

The amniotic fluids of 155 pregnant women, non-smokers (n = 128) and smokers (n = 27), were investigated on their cadmium (Cd) and lead (Pb) concentrations. The mean +/- s range of Cd in the amniotic fluid of non-smokers amounted to 2.58 +/- 1.36 ng/l, that of smokers to 7.29 +/- 2.39 micrograms/l. Moreover, there was a correlation between the extent of daily cigarette consumption and Cd levels. With Pb, higher concentrations were found ranging between 23.98 +/- 9.41 ng/l for non-smokers and 21.53 +/- 7.16 micrograms/l for smokers. No correlations were seen between age, week of pregnancy, blood pressure, disorders of pregnancy and the amniotic Cd or Pb concentrations. Thus, the maternal and fetal risks of the higher Cd levels in the amniotic fluid of smoking women remain unanswered.     

Evaluation of tumor necrosis factor-alpha and granulocyte colony-stimulating factor serum levels in lead-exposed smoker workers

Inorganic lead (Pb) is able to modulate the immune response even at low to moderate exposure levels. It inhibits in vitro and in vivo activities of neutrophil leucocytes and influences their blood count in humans. Neutrophil functions are governed by a number of cytokines. Pb has been shown to affect leukocyte production of some of these cytokines in vitro. The objective of this study is to assess serum tumor necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) levels of thirty-three male lead-exposed (E) workers at a lead recycling plant as compared with twenty-eight male non-exposed (NE) workers at a food processing plant, whose current smoking habit was known. Serum TNF-alpha and G-CSF levels were measured by a quantitative sandwich enzyme immunoassay. Blood lead levels (Pb-B) were significantly higher in E (geometric mean (GM) 30.7 microg/dl, GSD 1.7; min-max: 9.1-81.6 microg/dl) workers than controls (GM 3.6 microg/dl, GSD 1.7; min-max: 1.0-11.0 microg/dl). E workers had significantly higher serum TNF-alpha (median: 107.1; min-max: 11.1-623.0 pg/ml) and G-CSF levels (median: 53.0, min-max: 31.1-197.0 pg/ml) than NE workers (TNF-alpha: median: 12.0; min-max: 9.4-18.8 pg/ml; G-CSF: median: 34.3, min-max: 25.1-52.2 pg/ml). In particular, the TNF-alpha level was shown to be significantly influenced by lead exposure and smoking habit, as well as by interaction between these two factors. Both serum TNF-alpha and G-CSF levels were correlated with Pb-B and absolute neutrophil count. This study is the first to detect higher serum levels of G-CSF in E over NE workers. Our data confirm that exposure to low to medium doses of lead may interfere in the complex cytokine network involved in inflammation, especially in workers who are current smokers.     

The association between active/passive smoking and toxic metals among pregnant women in Greece

Exposure to toxic metals during pregnancy may have detrimental effects on foetal development. We assessed the role of sociodemographic characteristics and active and passive smoking on blood concentrations of metals (As, Cd, Pb, Hg, Sb, U, Mn and Mo). Venous blood drawn from 50 pregnant women, randomly selected from the mother-child birth cohort 'Rhea'. Extensive questionnaire data on active and passive smoking were collected. Urinary cotinine was measured to validate self-reported exposure and non-smoking status. Smokers had higher concentrations of Cd (1.0 μg/L) as compared with non-smokers (0.29 μg/L, P?相似文献   

Renal and hepatic accumulation of cadmium and lead in the expression of CYP4F2 and CYP2E1

The present study examined accumulation of the metal toxins cadmium (Cd) and lead (Pb) in relation to the abundance of cytochrome P450 4F2 (CYP4F2), CYP2E1 and concentrations of zinc and copper in liver and kidney samples using immunoblotting coupled with metal analysis. The post mortem liver and kidney cortex samples were from 23 males and 8 females aged 3-89 years. All were Caucasians who had not been exposed to metals in the workplace. Average kidney cortex Cd load of 17.4 microg/g w.w. was 17 times greater than average liver Cd load (1.1 microg/g w.w.). In contrast, average kidney cortex Pb load of 0.09 microg/g w.w. was two times lower than liver Pb load of 0.19 microg/g w.w. Average Zn and Cu concentrations in the kidney cortex samples were 67% and 33% lower than those in the liver. Liver and kidney Cd loads, but not liver or kidney Pb loads, correlated positively with donors' age. After controlling for liver Cd load, an inverse correlation was seen between Zn and age (partial r=-0.39, P=0.02), suggesting reduction in liver Zn levels in old age. Liver CYP2E1 protein abundance correlated with age-adjusted Cd load (partial r=0.37, P=0.02) whereas kidney CYP4F2 protein abundance showed a positive correlation with age-adjusted Cd loads (partial r=0.40, P=0.02). These findings suggest that Cd may be an inducer of renal CYP4F2 and hepatic CYP2E1 and that increased renal CYP4F2 expression may implicate in Cd-linked renal tubular dysfunction and high blood pressure, involving CYP4F2-dependent arachidonic acid metabolism.     

Potential human health risks from metals (Hg, Cd, and Pb) and polychlorinated biphenyls (PCBs) via seafood consumption: Estimation of target hazard quotients (THQs) and toxic equivalents (TEQs)

Edible marine species (fish, cephalopod molluscs, crustaceans) from the Adriatic Sea were analyzed for content in heavy metals (Hg, Cd and Pb) and polychlorinated biphenyls (PCBs). Health risks to human via dietary intake of seafood were assessed by the target hazard quotients (THQs) and the toxic equivalent factors (TEFs). Mercury maximum concentrations corresponded to fish (0.07-1.56 microg g(-1)w.w.), followed by cephalopod molluscs (0.10-0.55 microg g(-1)w.w.), and crustaceans (0.27-0.33 microg g(-1)w.w.). Cadmium levels in cephalopods (0.18-0.59 microg g(-1)w.w.) were higher than those in fish (0.01-0.05 microg g(-1)w.w.) and crustaceans (0.02-0.04 microg g(-1)w.w.), while for Pb the concentrations were generally low (fish: ND-1.18 microg g(-1)w.w., cephalopods: ND-0.17 microg g(-1)w.w., crustaceans: ND-0.03 microg g(-1)w.w.). For PCBs, concentrations in fish, cephalopods and crustaceans ranged between 141 and 3,406 ng g(-1)l.w., 190 and 542 ng g(-1)l.w., and 202 and 429 ng g(-1)l.w., respectively. Cd and Pb THQ values as well as estimates of PCB TEQ exposure indicated the absence of health risks through consumption of the various seafood. In contrast, mercury TEQs values due to consumption of certain fish species (albacore, rosefish and thornback ray) indicated that human health risk might be of concern.     

Co-exposure of cadmium and lead on bone health in a southwestern Chinese population aged 40-75 years

Both cadmium (Cd) and lead (Pb) are associated with bone health, but studies exploring the effects of Cd and Pb co-exposure on bone health are rare. This study aimed to assess the interactive effects of Cd and Pb co-exposure on bone health. In total, 799 participants, living in the targeted areas (located in southwestern China) for more than 15 years, aged 40-75 years, and subsisted on homegrown rice and vegetables were investigated. Cd and Pb levels in urine and blood samples, as well as bone mineral density, T- and Z-score were determined. After being adjusted for covariates, the T-score was negatively correlated with blood Pb in men (P < .05); for women and non-smoking women, the T-score was negatively correlated with urinary Pb (P < .05). Moreover, after being adjusted for covariates, the Z-score was negatively correlated with urinary Pb in non-smoking women (P < .05). No positive association of prevalence of osteoporosis with Cd and Pb exposure was found. However, at an additive scale, positive interactions of urinary Cd and Pb on the prevalence of osteoporosis for women and non-smoking women, and the same interactions to blood Cd and Pb for men were found. There was also a positive interaction of urinary Cd and Pb for women at a multiplicative scale. This study suggests Cd and Pb exposure could exert detrimental effects on bone health, with possible underlying interactions. Nevertheless, more studies are needed to explore the interactive effects of heavy metal co-exposure.     

Relation between occupational exposure to lead, cadmium, arsenic and concentration of cystatin C

Lead, cadmium and arsenic represent well recognized toxic agents which in a specific manner disturb function of cardiovascular system. Cystatin C has been accepted to be a significant prognostic factor for cardiovascular diseases. The study aimed at defining relationship between occupational exposure to lead, cadmium and arsenic on one hand and concentration of cystatin C on the other. The studies were performed on 282 men occupationally exposed to lead, cadmium and arsenic. Among the tested individuals several groups of persons were distinguished: exposed exclusively to lead (Pb group), cadmium (Cd group), arsenic (As group), to lead and cadmium (Pb/Cd group), to lead and arsenic (Pb/As group) or to cadmium and arsenic (Cd/As group). In all the individuals serum concentration of cystatin C was estimated. Concentration of cystatin C was found to be significantly higher in Pb group than in Cd and As groups, also in Pb/Cd group higher than in Cd group and in Pb/As group than in As group. Positive linear correlations were established between Pb concentration in blood (Pb-B) and serum concentration of cystatin C (r=0.59; p<0.05) as well as between urinary concentration of As (As-U) and serum concentration of cystatin C (r=0.41; p<0.05). Regression analysis demonstrated that higher blood level of lead, higher urinary level of arsenic, more advanced age and higher body mass index represented independent risk factors of an increased serum concentration of cystatin C in the group of persons exposed to lead, cadmium and arsenic. Conclusions: Higher blood level of lead and higher urinary level of arsenic represented independent risk factors of an increased serum concentration of cystatin C in the group of persons occupationally exposed to lead, cadmium and arsenic. Concentration of lead in blood was significantly influencing serum concentration of cystatin C. The highest mean serum concentration of cystatin C was detected in the group of foundry workers exposed simultaneously to lead and arsenic.     

Cadmium and nutritional intake in pregnant Japanese women

A study to clarify the food composition and nutritional factors that contribute to the levels of blood and urinary cadmium (Cd) was conducted on 50 pregnant Japanese women with mean age of 29 years. The mean iron (Fe) intake of subjects was 9.2 mg, which is much lower than the recommended level of 20 mg for pregnant women. Cd in urine samples collected at 30-32 weeks of gestation were correlated (r = 0.354), but urinary Cd was related to age more than blood Cd. Urinary Cd and blood Cd levels were inversely related to total energy (rpartial = -0.325, and -0.334, respectively) and fat intake (rpartial = -0.419, and -0.379, respectively), even after adjustment for age. Blood Cd was also correlated to protein and iron intake (rpartial = -0.299, and -0.353, respectively). These results indicate that Cd exposure levels of pregnant women with low energy intake, especially less fat intake, were higher than those of women with more energy and fat intake. In particular, blood Cd may be affected by protein and iron intake in pregnant women with increased these nutrients demand.     

DNA damage in workers exposed to lead using comet assay

Lead (Pb) is a ubiquitous and toxic metal. Secondary Pb recovery unit workers are prone to possible occupational Pb exposure. Hence, this investigation was conducted to assess the genotoxic effect of Pb exposure in these workers. In the study, 45 workers were monitored for DNA damage in blood leucocytes. Simultaneously 36 subjects were used as control group in this study. All the subjects were estimated for Pb content in whole blood by ICP-MS. The alkali single cell gel electrophoresis assay (comet assay) was adopted for detecting the DNA damage. The air inside the premises of the unit had Pb concentrations of 4.2 microg/m(3). The level of DNA damage was determined as the percentage of cells with comets. The mean Pb content was found to be significantly higher in the study group (248.3 microg/l) when compared with the controls (27.49 microg/l). Significantly more cells with DNA damage (44.58%) were observed in the study group than in the control persons (21.14%). Smoking had a significant effect on DNA damage in the control group whereas an insignificant effect was noticed in the exposed workers. Study as well as the control group failed to show a significant effect on DNA damage with age (P>0.05). Pb content and years of exposure significantly correlated with DNA damage in the study group (r=0.602, r=0.690; P<0.01). The increased levels of DNA damage observed in the exposed workers, justifies the use of the comet assay for the evaluation of genotoxic effects in humans exposed to Pb.     

Changes of lead levels in 24-h urine from 1985 to 1998 in Japanese adults

To determine whether current environmental lead (Pb) levels are causing any progressive changes in urinary Pb levels, 24-h urine samples were collected from 277 subjects (159 men and 118 women) in 1985, 312 subjects (155 men and 157 women) in 1993, and 311 subjects (156 men and 155 women) in 1998. All of the subjects worked in the same factory. The urinary Pb concentration was analyzed by flameless atomic absorption spectrophotometry. The geometric means for men were 4.74, 2.67 and 1.31 microg/day; 3.17, 1.78 and 1.04 microg/g creatinine; and 3.18, 1.99 and 0.98 microg/l urine in 1985, 1993 and 1998, respectively. The values for women were 3.22, 2.14 and 0.97 microg/day; 3.35, 2.26 and 1.15 microg/g creatinine; and 2.49, 1.86 and 0.83 microg/l urine, respectively. These results demonstrated that Pb levels in 24-h urine decreased significantly in the 13-year period (P<0.01).     

Estrogenic activity and reproductive effects of the UV-filter oxybenzone (2-hydroxy-4-methoxyphenyl-methanone) in fish

Previous studies in extracts of sediments surrounding municipal outfalls off the coast of California, USA and effluents of New York City, NY, USA indicated the UV-filtering agent, oxybenzone (CAS# 131-57-7; benzophenone-3) as a potential estrogen. The effects of oxybenzone on estrogenic activity and reproduction were evaluated using a 14-day juvenile rainbow trout assay for plasma vitellogenin and a subsequent 21-day Japanese medaka reproduction assay. Significant induction of vitellogenin was observed in the rainbow trout at the 1000 microg/L nominal concentration (749 microg/L median measured value) of oxybenzone which was approximately 75 times greater than the concentrations observed in previous wastewater effluent. Vitellogenin induction was also observed in the 1000 microg/L nominal concentration (620 microg/L median measured) of oxybenzone in male Japanese medaka (Oryzias latipes) after 21 days of exposure. The number of eggs produced per female per day exposed to the same concentration (620 microg/L) were significantly lower after 7 days, but returned to control values after 21 days. Fertilized eggs were then monitored for 20 days to assess hatching success. The overall percentage of fertilized eggs collected during the 21-day exposure that hatched was significantly lower in the 620 microg/L oxybenzone concentration. There was also a temporal effect at this concentration as egg viability (percentage of fertilized eggs that hatched) was diminished 13-15 days after eggs were collected. All three oxybenzone concentrations (16, 132, and 620 microg/L) and the 50 ng/L estradiol positive control showed reduced hatching of eggs at day 15, and the 132 and 620 microg/L oxybenzone concentrations diminished the percentage of eggs that hatched on days 13-15. These data indicate that the UV-filter oxybenzone alters endocrine or reproduction endpoints in two fish species, but at concentrations significantly higher than those measured in the environment.     

Evaluation of urinary cadmium and lead as markers of background exposure of middle-aged women in Korea: dietary intake as an influential factor.

The study was conducted to examine the validity of urinary cadmium (Cd) and lead (Pb) in comparison with the metals in blood as a biological marker of non-occupational exposure of general populations. Participants in four survey sites in Korea (107 non-smoking Korean women aged 30-49 years) offered peripheral blood, morning spot urine, and 24-h total food duplicate samples. Analysis of Cd and Pb was accomplished by graphite furnace atomic absorption spectrophotometry. The analyse levels were evaluated on an individual basis (n = 107) and also on a survey site basis, i.e. in terms of geometric means for the groups in the survey sites (n = 4). Cd in urine (as observed, or after correction for creatinine concentration or a specific gravity) correlated with Cd in blood on an individual as well as survey site basis, and tended to correlate with Cd in food duplicates on the survey site basis. Correlation of Pb in urine with Pb in blood was weaker than that of Cd in urine with Cd in blood both on the individual and survey site basis. Pb in urine correlated with Pb in food duplicates either weakly or even negatively when examined on a survey site basis. It was concluded that Cd in urine can be most probably employed as a biological marker of environmental Cd exposure of general population, whereas less support was obtained for Pb in urine as an exposure marker.     

Contribution of fish consumption to heavy metals exposure in women of childbearing age from a Mediterranean country (Spain).

The concentrations of cadmium (Cd), lead (Pb) and mercury (Hg) were determined in samples from sword-fish (Xiphias gladius, n=37) and louvar (Luvarus imperialis, n=17) taken in an official surveillance programme in Madrid (Spain). The levels of heavy metals were measured by atomic absorption spectrophotometry (hydride generator for Hg and flame atomic absorption for Cd and Pb) after digestion of the samples (microwave digestion for Hg and drying chamber for Cd and Pb). Pb contamination was negligible in both species. Cd was detected in 89.19% of the samples from sword-fish and 52.94% from louver; 17.65% of louvar and none from sword-fish being higher than maximum residue limits (MRL). However, around 90% of louvar samples and around 35% of sword-fish portions exceeded MRL for Hg; around 30% of louvar samples having levels even higher than 1 microg/g. The consumption of one serving of 150 g either of louvar or sword-fish would not be relevant for Cd and Pb provisional tolerable weekly intake (PTWI) of these elements for women in childbearing age, but it would largely exceed the tolerable values for Hg.     

Efficacy of succimer chelation for reducing brain lead in a primate model of human lead exposure

The extent to which succimer (meso-2,3-dimercaptosuccinic acid [DMSA], Chemet) reduces brain lead (Pb) levels may be a primary consideration in evaluating its efficacy for reducing neurotoxicity. Clinical research in this area has been hampered by the need to use blood Pb levels as the index of treatment efficacy, despite the fact that brain Pb level is the exposure parameter of greater relevance to cognitive outcomes. Here, a nonhuman primate model of human Pb exposure was used to determine: (1) The efficacy of oral succimer for reducing brain Pb derived from chronic or recent exposures, and (2) The extent to which blood Pb levels reflect brain Pb prior to and following chelation. Adult rhesus monkeys were chronically exposed to Pb orally for 5 weeks to reach and maintain a target blood Pb level of 35-40 microg/dL. Chelation of Pb from recent exposures was assessed using a stable (204)Pb isotope tracer administered over 4 days prior to treatment. Immediately prior to chelation, a prefrontal cortex (PFC) biopsy was collected to determine pretreatment brain Pb levels. Subsequently, monkeys were assigned to vehicle (n = 5) or succimer (n = 6, 30 mg/kg/day x 5 days followed by 20 mg/kg/day x 14 days) groups. Blood and brain PFC, frontal lobe (FL), hippocampus (H), and striatum (S) were analyzed for total Pb and (204)Pb tracer concentrations by magnetic sector inductively coupled plasma-mass spectrometry. There were no measurable differences in brain Pb concentrations between the succimer and vehicle groups, indicating that succimer treatment was not efficacious in reducing brain Pb levels. In contrast, the cessation of Pb exposure significantly reduced brain (PFC) Pb ( approximately 34%) when compared to pretreatment levels (succimer and vehicle groups). Pb concentrations also varied among brain regions (PFC > FL approximately H > S). Finally, pretreatment PFC Pb concentrations were significantly correlated with the integrated blood Pb level (AUC) over the Pb exposure period, but not with the single pretreatment blood Pb collected concurrently with the PFC biopsy. Following treatment, blood Pb levels correlated only with Pb in the PFC, and not the other brain regions measured (FL, H, S). These data indicate that, under the conditions of this study, succimer treatment did not reduce brain Pb levels beyond the cessation of Pb exposure alone. Moreover, a single blood Pb measurement may be a poor predictor of brain Pb levels, reflecting limitations in the use of blood Pb level as an indicator of treatment efficacy.     

A piglet model for studies of gastrointestinal uptake of cadmium in neonates

Newborns are believed to have a higher gastrointestinal uptake of inorganic cadmium (Cd) than adults. However, relevant models for investigations of absorption of dietary Cd in neonates are lacking. In the present study, piglets were exposed to 2 or 20 microg Cd/kg body weight (b wt) per day by repeated oral administrations of CdCl2 dissolved in deionized water or infant follow-up formula from days 0 to 10. Elevated and dose-dependent Cd retention in blood and tissues resulted from this low-dose Cd exposure, as determined at day 11. Follow-up formula reduced Cd uptake in comparison to deionized water. However, Cd distribution to the kidneys was higher when Cd was given in formula than in water. Metallothionein (MT) levels in liver, kidney and duodenum were six, three and two times higher, respectively compared to an un-exposed control. Differences in bioavailability and distribution of low-dose Cd given in various diets to newborns could be detected by the proposed piglet model.     

Cadmium-induced changes in luminal fluid pH in testis and epididymis of the rat in vivo

The effects of a single low subcutaneous dose of cadmium chloride (CdCl2) (2.7 mg/kg body weight) on in situ pH in the rat testis and epididymis, plasma testosterone, and testis and epididymis weights were investigated in this study. Values for in situ pH in seminiferous tubules (6.97 +/- 0.01), proximal caput (6.62 +/- 0.01), middle caput (6.59 +/- 0.01), and proximal cauda epididymidis (6.84 +/- 0.01) of sham-treated rats were significantly more acid than systemic arterial blood pH (7.41 +/- 0.01). Cadmium (Cd) administration was associated with significant alkalinization of luminal fluid in seminiferous tubules (7.17 +/- 0.02) and in proximal (7.02 +/- 0.04) and middle caput (6.99 +/- 0.03), but not in proximal cauda epididymidis (6.88 +/- 0.02), after 1 d. Eleven days after Cd administration, marked alkalinization of luminal fluid was observed in all segments studied including proximal cauda epididymidis (7.21 +/- 0.02). Plasma testosterone concentration in sham-treated rats was 1.93 +/- 0.30 ng/ml and was reduced significantly after 1 d (0.56 +/- 0.06 ng/ml) and persisted after 11 d postexposure (0.57 +/- 0.07 ng/ml). Testis and epididymis weights were not altered 1 d after Cd exposure but were significantly reduced after 11 d. These studies suggest that the alkalization observed in luminal fluid of seminiferous tubules and epididymal duct of the rat after subcutaneous CdCl2 administration may be the result of structural degeneration of the testis associated with inhibition of Leydig-cell androgen production.     

Estimation of benchmark doses as threshold levels of urinary cadmium, based on excretion of beta2-microglobulin in cadmium-polluted and non-polluted regions in Japan

The threshold level of urinary cadmium (Cd) for beta2-microglobulin (MG)-uria was calculated using a benchmark dose (BMD) approach. Total number of subjects was 3103 for Cd-polluted areas and 2929 for non-polluted areas. Multiple logistic regression analysis was employed to fit the dose-response model taking into consideration an age effect. Cut-off values for urinary beta2-MG were defined as those corresponding to the 84th and 97.5th percentile of beta2-MG levels in the controls, and 1000 microg/g creatinine (cr). The BMD low (BMDL) was calculated using the profile likelihood method. When the benchmark response was 5%, the BMD/BMDL of Cd for the 84th percentile of beta2-MG for mean age, 55, 65, and 75 years was 3.0/2.7, 4.6/4.2, 2.8/2.6, and 1.8/1.6 microg/g cr in men and 3.4/3.2, 5.8/5.5, 3.2/3.1, and 1.8/1.7 microg/g cr in women, respectively. The value for the 97.5th percentile for each age was 4.9/4.5, 7.6/7.0, 4.6/4.3, and 2.6/2.4 microg/g cr in men and 5.9/5.6, 9.7/9.2, 5.6/5.3, and 2.8/2.6 microg/g cr in women. Namely it became clear that the margin between the threshold level and average excretion level of urinary Cd was small in the older population in Japan. To prevent the adverse health effects caused by exposure to Cd, it is important to establish the threshold level of Cd exposure at each age.