[Uncertain timing trend in connection with cadmium exposure].
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Adolescent↗
Biomedical subjects
M Vahter
Publications and source records attributed to M Vahter.
Exposure to inorganic arsenic metabolites during early human development.
Because of the lack of data on the exposure to and toxic effects of inorganic arsenic during early human development, the transfer of arsenic to the fetus and suckling infant was studied in a native Andean population, living in the village San Antonio de los Cobres in the North west of Argentina, where the drinking water contains about 200 micrograms/liter. The concentration of arsenic in cord blood (median, 9 micrograms/liter) was almost as high as in maternal blood (median, 11 micrograms/liter), and there was a significant correlation between the two. Thus, at least in late gestation, arsenic is easily transferred to the fetus. The median concentration of arsenic in the placenta was 34 micrograms/kg, compared with 7 micrograms/kg previously reported for nonexposed women. Interestingly, essentially all arsenic in the blood plasma of both the newborns and their mothers was in the form of dimethylarsinic acid (DMA), the end product of inorganic arsenic metabolism. Similarly, about 90% of the arsenic in the urine of both the newborns and mothers in late gestation was present as DMA, compared with about 70% in nonpregnant women (p < 0.001). This may indicate that methylation of arsenic is increased during pregnancy and that DMA is the major form of arsenic transferred to the fetus. The increased methylation in late gestation was associated with lower arsenic concentrations in blood and higher concentrations in urine, compared with a few months postpartum. The arsenic concentrations in the urine of the infants decreased from about 80 micrograms/liter during the first 2 days of life to less than 30 micrograms/liter at 4.4 months (p = 0.025). This could be explained by the low concentrations of arsenic in the breast milk, about 3 micrograms/kg.
Arsenic↗
Low-level arsenic excretion in breast milk of native Andean women exposed to high levels of arsenic in the drinking water.
OBJECTIVE: To investigate the excretion of arsenic in breast milk of lactating native Andean women living in a village in northwestern Argentina with high concentrations of arsenic in the drinking water (about 200 micrograms/l) and to assess the exposure of children to arsenic during the very first period of life. METHODS: The study included ten lactating women and two nursing babies. Hydride-generation atomic absorption spectrometry (HG-AAS) was used to determine the concentration of arsenic in samples of human milk, drinking water, blood, and urine. RESULTS: The concentrations of arsenic detected in maternal blood (total arsenic) and urine (metabolites of inorganic arsenic) were high, averaging 10 and 320 micrograms/l, respectively. In subjects without known exposure to arsenic the average concentrations found in blood and urine are 1-2 and about 10 micrograms/l, respectively. The metabolites of inorganic arsenic constituted more than 80% of the total arsenic in the urine, which shows that inorganic arsenic was the main form of arsenic ingested. The average concentration of arsenic detected in human milk was 2.3 micrograms/kg fresh weight (range 0.83-7.6 micrograms/kg). Although data on background levels of arsenic in human breast milk are scarce, the present concentrations seem to be slightly elevated. However, considering the high levels of arsenic exposure in the mothers, the total arsenic concentrations measured in human milk were low. In concordance with the low concentrations of arsenic found in the milk, the concentrations of arsenic metabolites measured in the urine of two of the nursing babies were low: 17 and 47 micrograms/l, respectively. CONCLUSIONS: The low concentrations of arsenic detected in the breast milk and urine of the two nursing babies in relation to the high level of maternal exposure to arsenic indicate that inorganic arsenic is not excreted in breast milk to any significant extent. This is a very important reason for long breast-feeding periods.
Adolescent↗
Exposure to lead and other metals in children from Katowice district, Poland.
OBJECTIVES: To assess the exposure to toxic metals and to evaluate its possible association with essential elements and socioeconomic status in children from the town of Bytom in the Katowice area; this area is one of the most polluted industrialized regions in Poland. METHODS: Concentrations of lead, cadmium, mercury, selenium, magnesium, copper, and zinc were determined in whole blood of 211 children aged 9 years. The samples were analyzed using inductively coupled plasma mass spectrometry (ICP-MS). Information on socioeconomic factors was collected using questionnaires. Concentrations of trace elements in the blood of 24 Swedish children aged 9-10 years were used for comparisons. RESULTS: The concentrations of lead detected in the blood of the Polish children ranged from 0.09 to 1.9 mumol/l, with the median value being 0.27 mumol/l. Statistically significant associations were found between lead and such socioeconomic factors as the number of siblings, trips outside the region, maternal smoking, playing outdoors, and apartment standard. The average blood lead level was about 3 times higher in the Polish children than in the Swedish group. The median blood concentration of cadmium found in the Polish children was 3.4 nmol/l (range 1.1-41 nmol/l; almost 3 times higher than that detected in the Swedish children), and that of mercury was 3 nmol/l (range 0.5-11 nmol/l). The median blood levels and ranges of the essential elements were 1.1 (0.7-2.0) mumol/l for selenium, 1.5 (1.2-1.9) mmol/l for magnesium, 17 (13-22) mumol/l for copper, and 78 (54-104) mumol/l for zinc, respectively. The concentrations of selenium and magnesium were significantly lower in the Polish group as compared with the Swedish children. CONCLUSIONS: In all, 7% of the Polish children had blood lead levels exceeding 0.5 mumol/l, the concentration above which negative effects on mental development have been reported. However, the findings indicate a decrease in lead exposure during recent years among the Bytom children.
Child↗
Interactions between essential and toxic elements in lead exposed children in Katowice, Poland.
OBJECTIVES: To determine the influence of the essential element status on blood concentrations of lead and other toxic metals. DESIGN AND METHODS: A group of 157 children from Katowice, an industrial area in Poland, was investigated for concentrations of lead and cadmium in whole blood, and mercury, selenium, zinc, copper, and magnesium in whole blood and serum. Relations between these elements, serum ferritin, hematological parameters, as well as serum selenoprotein P and glutathione peroxidase (GSH-px) were examined. Conversion factors for element concentrations (mumol to microgram): lead 207.19, cadmium 112.41, mercury 200.59, selenium 78.96, magnesium 24.31, copper 63.55, and zinc 65. RESULTS: Blood lead was negatively associated with concentrations of selenium in whole blood and serum as well as selenoprotein P and glutathione peroxidase in serum. The association was mainly apparent at low blood lead concentrations, which may indicate an influence of selenium on the kinetics of lead, rather than an effect of lead on the selenium status. Children with low serum ferritin levels had statistically higher blood cadmium levels and a tendency for higher blood lead levels, indicating increased gastrointestinal absorption of these metals at reduced iron stores. Blood lead was negatively correlated with mean corpuscular hemoglobin concentration, which may reflect the effect of lead on hemoglobin synthesis. There was an association between blood mercury and selenium, indicating a common source of intake through fish consumption. CONCLUSIONS: The results indicate that selenium and iron status may influence the kinetics of lead.
Adolescent↗
Validation with biological markers for food intake of a dietary assessment method used by Swedish women with three different dietary preferences.
OBJECTIVES: To validate a dietary assessment method, a 4-day food record together with a duplicate portion technique, with biological markers for food intake. DESIGN: Four days of duplicate portions were collected in parallel with food recording. A 24-h urine sample and the faeces corresponding to the food intake (using a coloured marker) were collected. Completeness of urine and faeces collections was assessed using para-aminobenzoic acid (PABA) in urine and cadmium in faeces, respectively. Biomarkers of food intake (energy, protein, fibre, sodium, potassium, calcium) were measured in urine and faeces. SETTING: Swedish west coast. SUBJECTS: Non-smoking Swedish women, 20-50 years of age, consuming a mixed diet (n = 34), a mixed diet rich in shellfish (n = 17) or a vegetarian/high-fibre diet (n = 23). RESULTS: The average ratio (food intake according to the dietary assessment methods/ biological marker) for protein, sodium, potassium and calcium was 0.86. This indicates an underestimation of the food intake by approximately 15%. The ratio of stated fibre intake to biological marker was 1.20 for the mixed diet and the vegetarian diet group, indicating an overestimation by approximately 20%. CONCLUSIONS: The underestimation of the intake of protein, sodium, potassium and calcium by all three groups and the overestimation of the fibre intake by two groups indicate that underreporting is selective to certain nutrients and foods and to various groups of people. The two dependent dietary assessment methods were equally good in measuring protein intake, which indicates that the women recorded what they actually duplicated.
4-Aminobenzoic Acid↗
Serum transferrin receptor: a specific marker of iron deficiency in pregnancy.
BACKGROUND: Current markers of iron deficiency tend to be less reliable in pregnancy. OBJECTIVE: Our aim was to study the usefulness of soluble serum transferrin receptor (sTfR) as a marker for iron deficiency during early and late gestation and to define iron status in 254 pregnant Swedish women. DESIGN: We performed a cross-sectional and longitudinal evaluation of sTfR in comparison with concentrations of serum ferritin and hemoglobin in blood collected around gestational weeks 11 and 36. RESULTS: The specificity of sTfR was 100%. The sensitivity in relation to both anemia and depleted iron stores was approximately 70%, but this figure is less reliable because of few samples. sTfR in early pregnancy was low: 11% of women had a value below the reference interval. sTfR increased significantly from early to late pregnancy even in the group of women with persisting iron stores. In late pregnancy, 14% of women developed tissue iron deficiency and 5% had iron deficiency according to a combination of all 3 markers. CONCLUSIONS: sTfR seems to be a specific and sensitive marker of iron deficiency in pregnancy and may have advantages over serum ferritin and hemoglobin. The low sTfR concentration in early gestation seems to be caused by reduced erythropoiesis, whereas the increase from early to late pregnancy reflects increased erythropoiesis, and in case of iron deficiency, also tissue iron deficiency. Further studies are needed to verify whether decreased erythropoiesis reduces the possibility of detecting iron deficiency during early gestation by sTfR.
Anemia↗
Cross-fostering study of methyl mercury retention, demethylation and excretion in the neonatal hamster.
The cross-fostering technique was used in order to compare methyl mercury (MeHg) metabolism in hamsters following prenatal (in utero) and neonatal (lactational) exposure. Pregnant Syrian golden hamsters were administered radiolabeled MeHg on day 12 of gestation. The offspring was nursed by foster mothers unexposed to MeHg, while the pups from the unexposed animals were nursed by the MeHg-administered animals. Under these conditions, each pup in the litter received a dose of MeHg in utero corresponding to 0.9% of the maternal dose. The average amount of mercury found in the pups exposed via milk corresponded to 4.5% of the total body burden of the foster dam at the onset of lactation. This was about half the amount received by the pups exposed in utero. The total body burden of mercury, and the amount of mercury in the liver, brain and kidney of the pups exposed in utero began to decrease at seven days of age. The rate of decrease differed among the tissues and was lowest in the kidney. The amount of mercury in pups exposed via milk reached a peak level when the pups were 10-15 days old. The total body burden of mercury showed a slow decrease while the liver, brain and kidney levels decreased rapidly. In both groups of animals, up to 80% of the total body burden of mercury was found in the pelt. These data show that milk may be a significant exposure route for mercury and that neonatal hamsters are unable to demethylate MeHg and excrete mercury in urine and faeces.
Animals↗
Health effects of cadmium exposure--a review of the literature and a risk estimate.
This report provides a review of the cadmium exposure situation in Sweden and updates the information on health risk assessment according to recent studies on the health effects of cadmium. The report focuses on the health effects of low cadmium doses and the identification of high-risk groups. The diet is the main source of cadmium exposure in the Swedish nonsmoking general population. The average daily dietary intake is about 15 micrograms/day, but there are great individual variations due to differences in energy intake and dietary habits. It has been shown that a high fiber diet and a diet rich in shellfish increase the dietary cadmium intake substantially. Cadmium concentrations in agricultural soil and wheat have increased continuously during the last century. At present, soil cadmium concentrations increase by about 0.2% per year. Cadmium accumulates in the kidneys. Human kidney concentrations of cadmium have increased several fold during the last century. Cadmium in pig kidney has been shown to have increased by about 2% per year from 1984-1992. There is no tendency towards decreasing cadmium exposure among the general nonsmoking population. The absorption of cadmium in the lungs is 10-50%, while the absorption in the gastrointestinal tract is only a few percent. Smokers have about 4-5 times higher blood cadmium concentrations (about 1.5 micrograms/l), and twice as high kidney cortex cadmium concentrations (about 20-30 micrograms/g wet weight) as nonsmokers. Similarly, the blood cadmium concentrations are substantially elevated in persons with low body iron stores, indicating increased gastrointestinal absorption. About 10-40% of Swedish women of child-bearing age are reported to have empty iron stores (S-ferritin < 12 micrograms/l). In general, women have higher concentrations of cadmium in blood, urine, and kidney than men. The population groups at highest risk are probably smokers, women with low body iron stores, and people habitually eating a diet rich in cadmium. According to current knowledge, renal tubular damage is probably the critical health effect of cadmium exposure, both in the general population and in occupationally exposed workers. Tubular damage may develop at much lower levels than previously estimated, as shown in this report. Data from several recent reports from different countries indicate that an average urinary cadmium excretion of 2.5 micrograms/g creatinine is related to an excess prevalence of renal tubular damage of 4%. An average urinary excretion of 2.5 micrograms/g creatinine corresponds to an average concentration of cadmium in renal cortex of 50 micrograms/g, which would be the result of long-term (decades) intake of 50 micrograms per day. When the critical concentrations for adverse effects due to cadmium accumulation are being evaluated, it is crucial to consider both the individual variation in kidney cadmium concentrations and the variations in sensitivity within the general population. Even if the population average kidney concentration is relatively low for the general population, a certain proportion will have values exceeding the concentration where renal tubular damage can occur. It can be estimated that, at the present average daily intake of cadmium in Sweden, about 1% of women with low body iron stores and smokers may experience adverse renal effects related to cadmium. If the average daily intake of cadmium would increase to 30 micrograms/day, about 1% of the entire population would have cadmium-induced tubular damage. In risk groups, for example, women with low iron stores, the percentage would be higher, up to 5%. Both human and animal studies indicate that skeletal damage (osteoporosis) may be a critical effect of cadmium exposure. We conclude, however, that the present evidence is not sufficient to permit such a conclusion for humans. We would like to stress, however, that osteoporosis is a very important public health problem worldwide, but especially in the Scandinav
Animals↗
The semiconductor elements arsenic and indium induce apoptosis in rat thymocytes.
Indium arsenide and gallium arsenide are important new materials in the semiconductor industry due to their superior electronic properties in comparison with the older silicon-based materials. Animal experiments have shown that exposure to these compounds induces marked alterations in gene expression and immune response. Toxicity to the immune system has frequently been related to T and B cell apoptosis. In the present study we show that the semiconductor elements indium (In) and arsenic (As) are able to induce apoptosis in rat thymocytes in vitro. The results show that exposure to InCl3 (1, 10, or 100 microM) or Na AsO2 (0.01, 0.1, or 1 microM) induced DNA laddering after 6 h of incubation without compromising cell viability. These results were corroborated by flow cytometry analysis of propidium iodide-loaded cells, showing a typical high hypodiploid DNA peak in apoptotic thymocytes. Higher doses of In (1 mM) or As (10-100 microM) induced cell death by necrosis. These data indicate that In and As can induce apoptosis and necrosis in T lymphocytes in a dose-dependent manner, which may be of relevance for their immunotoxicity.
Animals↗
Extensive lead exposure in children living in an area with production of lead-glazed tiles in the Ecuadorian Andes.
We have determined the concentrations of lead (Pb), cadmium (Cd), and mercury (Hg) in the blood of children living in two Andean villages in Ecuador with many family-owned cottage-type industries using Pb from discarded car batteries and occasionally, utility batteries containing Cd and Hg for the production of glazed tiles. The battery metals are ground together with water to a suspension, which is applied manually onto the tiles and then fused at about 1,200 degrees C in sawdust-fired kilns. Children aged 4-15 years were recruited from the schools with the assistance of the school-teachers. Children from homes with and without tile-glazing activities were to be included. Blood metal concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS). The children had extremely high blood lead concentrations (B-Pb), which ranged between 100 and 1,100 micrograms/l (median 510 micrograms/l, n = 82). Children from families engaged in tile-glazing production had significantly higher B-Pb (median 600 micrograms/l) than those living in homes with no such activity (median 210 micrograms/l), although the B-Pb of the latter were nonetheless clearly elevated. B-Cd and B-Hg were low (medians 0.25 microgram Cd/l and 1.6 micrograms Hg/l, respectively), indicating that the exposure from utility batteries containing Cd and Hg was low. The blood hemoglobin concentrations decreased significantly with rising B-Pb, indicating an effect on the heme synthesis. This was supported by a marked increase in the blood concentration of protoporphyrins with increasing B-Pb. It can be concluded that children from families with cottage industries producing glazed tiles are at risk for severe health effects due to high lead exposure.
Adolescent↗
Concentrations of copper, zinc and selenium in brain and kidney of second trimester fetuses and infants.
The concentrations of copper (Cu), zinc (Zn) and selenium (Se) in the brain and kidneys of second trimester fetuses (abortion cases) and infants (deceased before three months of age) were determined. Concentrations of Cu in brain, 0.31-1.6 mg/kg wet weight, increased with age, and were, on the average, three times higher in the brains of infants than of fetuses. In kidneys, Cu concentrations ranged between 0.34 and 2.9 mg/kg, and increased with age after birth. Concentrations of Zn in the brain decreased significantly with age in the fetuses, from about 7 mg/kg at post-conceptional week 12 to less than 5 mg/kg at week 20, but increased again postnatally. In kidneys, Zn concentrations (12-37 mg/kg) increased in parallel with the increase in tissue density. Concentrations of Se in brain, 0.072-0.14 mg/kg, decreased with age in the fetuses, but increased with age postnatally. Kidney Se concentrations (0.16-0.55 mg/kg) did not change significantly with age during the fetal period, but increased about 2.5 times during the postnatal period. There was a significant association between the concentrations (on molar basis) of Zn and Cu in kidneys, but not in brain. There was no correlation between the concentrations of Cu, Zn or Se and those of mercury, cadmium and lead, previously determined in the same samples, with the exception of mercury and Se in kidneys.
Brain↗
Inorganic mercury modifies Ca2+ signals, triggers apoptosis and potentiates NMDA toxicity in cerebellar granule neurons.
Hg2+ (0.1 microM-0.5 microM) modified the Ca2+ signals elicited by either KCl or the glutamate-receptor agonist, N-methyl-D-aspartate (NMDA), in cerebellar granule cells (CGCs). Hg2+ enhanced the intracellular Ca2+ transient elicited by high K+ and prevented a complete recovery of the resting intracellular Ca2+ concentration ([Ca2+]i) after either KCl or NMDA stimulation. Higher Hg2+ concentrations (up to 1 microM) increased [Ca2+]i directly. Following the short-term exposure to Hg2+, CGCs underwent apoptosis, which was identified by the cleavage of DNA into large (700-50 kbp) and oligonucleosomal DNA fragments, and by the appearance of typical apoptotic nuclei. Combined treatment with 0.1-0.3 microM Hg2+ and a sublethal NMDA concentration (50 microM) potentiated DNA fragmentation and apoptotic cell death. When the exposure to Hg2+ was carried out in Ca2+-free media or in the presence of Ca2+ channel blockers (L-type or NMDA-R antagonists), the effects on signalling and apoptosis were prevented. Our results suggest that very low Hg2+ concentrations can trigger apoptosis in CGCs by facilitating Ca2+ entry through membrane channels.
Journal Article↗
High lead exposure and auditory sensory-neural function in Andean children.
We investigated blood lead (B-Pb) and mercury (B-Hg) levels and auditory sensory-neural function in 62 Andean school children living in a Pb-contaminated area of Ecuador and 14 children in a neighboring gold mining area with no known Pb exposure. The median B-Pb level for 62 children in the Pb-exposed group was 52.6 micrograms/dl (range 9.9-110.0 micrograms/dl) compared with 6.4 micrograms/dl (range 3.9-12.0 micrograms/dl) for the children in the non-Pb exposed group; the differences were statistically significant (p < 0.001). Auditory thresholds for the Pb-exposed group were normal at the pure tone frequencies of 0.25-8 kHz over the entire range of B-Pb levels, Auditory brain stem response tests in seven children with high B-Pb levels showed normal absolute peak and interpeak latencies. The median B-Hg levels were 0.16 micrograms/dl (range 0.04-0.58 micrograms/dl) for children in the Pb-exposed group and 0.22 micrograms/dl (range 0.1-0.44 micrograms/dl) for children in the non-Pb exposed gold mining area, and showed no significant relationship to auditory function.
Adolescent↗
Chromosomal aberrations in peripheral blood lymphocytes from native Andean women and children from northwestern Argentina exposed to arsenic in drinking water.
For conducting an adequate human cancer risk assessment of inorganic arsenic (As) in the low-dose region, it is important to establish its mode of action. In this context, the nature of genotoxic effects induced by this agent is of considerable interest. However, the results from such investigations in human have been conflicting. In an attempt to resolve this issue, the clastogenic and aneugenic potential of As was investigated in women and children from native population exposed to high levels (around 0.2 mg/l) of natural As via drinking water in San Antonio de los Corbes in the Andean region of Salta, Northwestern Argentina. The water did not contain elevated levels of heavy metals, such as lead or cadmium, nor was the investigated population exposed to significant industrial pollution or to pesticides. An ethnically similar control group from Rosario de Lerma, Salta, where only extremely low concentration of arsenic in drinking water could be detected, was used as a control. To evaluate the genotoxic effects in peripheral blood lymphocytes, micronuclei (MN) in binucleated cells, sister-chromatid exchanges (SCEs) and the fluorescence in situ hybridization technique (FISH) in combination with chromosome specific DNA libraries were employed. The data obtained clearly indicate a highly significant increase in the frequency of MN and of trisomy in lymphocytes from exposed children and women in comparison with controls, but no notable effects were found on the frequencies of SCEs, specific translocations, or on cell cycle progression. As supported by FISH analysis, at least a proportion of MN appears to originate from whole chromosome loss. An additional finding was the unusually low background levels of MN in unexposed individuals from this ethnic group as compared to other populations, e.g., Caucasians.
Adolescent↗
Bioavailability of cadmium from shellfish and mixed diet in women.
Dietary intake and uptake of cadmium (Cd) were studied in nonsmoking women, 20-50 years of age, consuming a mixed diet low in shellfish (N = 34) or with shellfish once a week or more (N = 17). Duplicate diets were collected during 4 consecutive days for the determination of Cd content. The women kept detailed dietary records, and the intake of energy and various nutrients was calculated. The shellfish diets (median 22.3 micrograms Cd/day) contained twice as much Cd as the mixed diets (median 10.5 micrograms Cd/day; p < 0.0001). Cadmium in feces corresponded to 100 and 99% of that in duplicates of shellfish diets and mixed diets, respectively, indicating a low average absorption of the dietary Cd. In spite of the differences in the daily intake of Cd, there was no statistically significant difference in the concentrations of Cd in blood (B-Cd, shellfish group 0.25 micrograms/liter, mixed diet group 0.23 micrograms/liter) or urine (U-Cd, 0.10 micrograms Cd/liter in both groups). This indicates a lower absorption of Cd in the shellfish group than in the mixed diet group or a difference in the kinetics. A higher gastrointestinal absorption of Cd in the mixed diet group could partly be explained by lower body iron stores as measured by the concentrations of serum ferritin (S-fer, median 18 micrograms/liter, compared to 31 micrograms/liter in the shellfish group). In the mixed diet group, S-fer was negatively correlated with B-Cd and the main determining for B-Cd besides U-Cd in the multiple regression analysis, indicating an increased absorption of Cd at low body iron stores. When women with S-fer exceeding 20 micrograms/liter were compared, the higher dietary intake of Cd in the shellfish group compared to the mixed diet group (24 versus 10 micrograms/day) resulted in higher B-Cd (0.26 versus 0.16 micrograms/liter), although not in proportion to the difference in Cd intake. Thus, there seems to be differences in the bioavailability and/or kinetics of dietary Cd related to the type of diet. This is, to our knowledge, the first study where the influence of various types of diets and nutritional factors on the intake and uptake of cadmium in human subjects has been studied.
Adult↗
A physiologically based pharmacokinetic model for arsenic exposure. I. Development in hamsters and rabbits.
A physiologically based pharmacokinetic model for exposure to inorganic arsenic in hamsters and rabbits has been developed. The model in its present state simulates three routes of exposure to inorganic arsenic: oral intake, intravenous injection, and intratracheal instillation. It describes the tissue concentrations and the urinary and fecal excretions of the four arsenic metabolites: inorganic As(III) and As(V), methylarsonic acid, and dimethylarsinic acid. The model consists of five tissue compartments, chosen according to arsenic affinities: liver, kidneys, lungs, skin, and others. The model is based on physiological parameters, which were scaled according to body weight. When physiological parameters were not available, the data for the model were obtained by fitting (tissue affinity, absorption rate, and metabolic rate constants). The excretions of the arsenic metabolites in urine and feces are well simulated with the model for both species. Further validation of the arsenic metabolite concentrations in the tissues and in vitro measurements of the tissue affinity constants are discussed.
Administration, Oral↗
A physiologically based pharmacokinetic model for arsenic exposure. II. Validation and application in humans.
A physiologically based pharmacokinetic model (PB-PK) for inorganic arsenic exposure in humans has been developed. This model is an extension of a PB-PK model for hamsters and rabbits, with adjustments for body weight, metabolic rates, and absorption rates. It describes the absorption, distribution, metabolism, and excretion of arsenate, arsenite (As(III)), methyl arsonate, and dimethyl arsinate, the four major metabolites of inorganic arsenic. The routes of intake considered are inhalation of arsenic dust and fumes and oral intake of arsenic via drinking water and food. The PB-PK model for the oral exposure route is validated using data on urinary excretion after repeated oral exposure to As(III) as well as after exposure to inorganic As via drinking water. Absorption by inhalation is validated using data on urinary excretion after occupational exposure to arsenic trioxide dust and fumes. In both cases, the model gives satisfactory results for urinary excretion of the four As metabolites. The PB-PK model is also used in the description of the effects on the kinetics of exposure via different routes and for the simulation of various realistic exposure scenarios.
Administration, Inhalation↗