Impact of Cadmium on Human Health

 Risk assessment of effects of cadmium on human health (IUPAC Technical Report

Cadmium is a metallic element of Group 12 (Zn, Cd, Hg) of the Periodic table, Cadmium has a valence of +2, it participates some characteristics with its brothers in group 12. Mercury is a very toxic element, it has the highest atomic mass however, and zinc has the lower atomic mass as brothers in the periodic table with mercury and cadmium.

As physiochemical properties, cadmium is scentless, flexible, and fine and it has a bluish –white or silvery-white luster. There is (0.1–0.5) mg kg−1 of cadmium, it’s a scarce element, it can’t be found as one element in the environment, it’s an element that is mixed with a group of other elements, it’s isolated by Stromeyer for the first time, it has many uses in our daily life such as industrial, smelting, and mining that result in a high bio-accessibility in the nature especially the anthropogenic sources that impendence the human health

Cadim has been checked by UNEP and IPCS chemical branches, they have evaluated that is a profanation for the nature. A section on initiatives and actions for the administration and monitoring over the release of and exposures to cadmium, including the human life continuity, and the national and international companies considered the nature to be important enough to need arrangement has been reported by the UNEP.

Cadmium oxide produced by a swift oxidation of cadmium vapor. Salts that may enter the nature are derived from the reaction of cadmium with gases and vapors like water vapor, sulfur dioxide, carbon dioxide, hydrogen chloride, and sulfur trioxide. Cadmium forms many inorganic salts which are similar to the zinc compounds in their characteristics.

The soluble salts, insoluble pigments, and those compounds that are insoluble at neutral pH but dissolve in dilute acid are the three groups of cadmium compounds. The chalcogenides are insoluble in water, while the halides, the nitrate, and sulfate of cadmium have a high solubility in water. The hydroxide and the carbonate are soluble only in dilute acid. Cadmium selenosulfide (orange), cadmium selenide (red), and cadmium sulfide (yellow), are used as pigments, singly or in combination. Cadmium sulfide, nanoparticles of cadmium selenide, and cadmium selenide can be used in electronic equipment and solar panels. Cadmium, carbonate and cadmium hydroxide should be soluble at the acidic pH prevailing in the human stomach and are soluble in dilute acid.

1. Toxicokinetic

1.1 Absorption and uptake

The uptake of cadmium after inhalation and ingestion were studied in the following parts. With respect to the uptake of cadmium in humans, the dermal   uptake corresponds to a small part of the total uptake.

1.2 Inhalation

Many reasons can affect the absorption of inhaled cadmium in the respiratory tract including the solubility if cadmium species and the size of inhaled cadmium bearing particles. According to the experiments on animals it’s clear that between 7 and 40 percent of an inhaled aerosol of cadmium was absorbed to the blood, small particles with high solubility are the high values , and the large particles with low solubility are the low values. General knowledge about the deposition and absorption of particle aerosols in human lungs allow making calculations that give us the same uptake evaluation. These calculations show that ultrafine particles of cadmium can represent up to 50 percent of the uptake, example cigarette smoke. Nano-sized forms of   cadmium particles can also arise in the nose and pharynx.

1.1.1 Ingestion

According to a population data from USA and results with a Toxicokinetics mode, after ingestion of cadmium it has been evaluated to be, on mean, 5 percent of the food component among men and 10 percent among women .According to the same computation, the values measured on 30 persons in Sweden using kidney cortex, blood, and urine that allowed Fransson et al., 2014 to announce lower evaluations. It’s clear that in Sweden there is a low intake of cadmium with respect to other countries of high intake. Animal studies show dependence on strong doses, with higher gastrointestinal intake and holding of cadmium at higher doses. In humans iron doses can affect cadmium intake from the diet, as ferritin uptake in diet decrease below 20 ug L-1, cadmium intake increase in blood or urine in women and storage of iron decrease in human body. Men have higher storage of iron than women that’s why they have a high intestinal uptake of cadmium and the bio monitoring media contain large concentrations of cadmium. Other factors that affect cadmium intake like protein, fiber, calcium, zinc, and iron were collected from animal studies,  the combination with essential elements also take place in humans these metals are mentioned since cadmium utilizes the same intestinal transporters as zinc, iron , and calcium. An up –regulation of DMT1 (Divalent Metal Transporter 1) cause the high cadmium uptake followed by low iron intake. As animal experiments show that calcium deficiency increase cadmium intake, this low contribution of calcium in the diet will cause a change in the bones that is noted in Itai-itai diseases as cadmium concentrations become higher. Other studies reveal that the effect of low dietary calcium uptake on the intestinal cadmium uptake has not been reported in human being.

1.1 Transport and distribution

As cadmium absorbed to the blood it’s transported to other tissues, its founded in the blood cells, but for transfer to body parts cadmium in blood plasma is more important. Cadmium is allocated by plasma to many organs, but the blood brain blocker save the brain from high concentrations and the placental impediment preserve the fetus. In plasma , cadmium is half confined to low molecular mass protein and half confined to high molecular mass protein . The low molecular mass protein is mainly albumin in which cadmium allocated to it is transferred to the liver. The cadmium bound to albumin may also bind to metallothionein (MT) it’s a small protein that contain a high sulfhydryl groups. Those confined to MT is separated by the glomeruli of the kidneys and resorbed through the kidney tubules, where cadmium is collected. Glutathione and cysteine are complexes with non-protein sulfhydryl’s that is formed in response to cadmium that is not bound to protein in plasma. In Sweden, humans with a typical dietary exposure (estimated at 12 ug day-1), 50 percent of the body load is found in the kidneys and 15 percent in the liver. However in other communities with high exposure such as Japan in the 1960s and 1970s (60-113 ug day-1), the highest concentration is in the liver and lower concentration is in the kidneys .In general cadmium is higher in the kidneys, it increase more with age, specifically its more accumulated in women than in men, and in smokers than in nonsmokers. Since low iron amount with high cadmium absorption in women lead to an accumulation of cadmium in the kidneys. 

1.3 Excretion, biological half-life

 Only a very small proportion of the body burden of cadmium is excreted by humans each day. The relationship between the concentration of cadmium in the kidney and urine cadmium concentration is discussed in Section 6.1.2. There is a dramatic increase in the proportion of     cadmium excreted in urine when renal damage is induced by cadmium. Measurements of concentrations of cadmium in human tissues, in combination with measurements of excretion at various ages, indicate that the biological half-life of cadmium is 10-30 years in muscle, kidney cortex, and liver tissue.

In blood, the biological half-life has two components according to studies by Jarup et al. Animal experiments show that the biological half-life is dependent on exposure level. At doses below the level that induces renal tubular dysfunction, the clearance of cadmium is slightly slower as dose increases, probably because a larger proportion of tissue cadmium is bound to metallothionein at higher doses, promoting tissue retention. In addition, there was a positive intercept for the relationship between urine cadmium and body burden of cadmium in these animal studies.

This observation may be explained if there is a direct route for cadmium to pass from blood plasma to urine and the amount excreted by this route is related to recent exposure. 8 mg kg−1 and 43 years at 23 mg kg−1, based on the slope of the observed linear relationship between the urine excretion rate and the kidney cadmium burden . These estimates reflect the combined contributions of all urinary pathways for cadmium, including transfer from plasma and transfer from kidney tissue. The longer half time at higher kidney tissue cadmium levels suggests that slow transfer from kidney tissue to urine dominates urine cadmium kinetics when kidney tissue levels are high ., 2014 calculated the rate of transfer of cadmium from kidney tissue to urine by estimating this parameter in a physiologically based Toxicokinetics model , based on the data from Akerstrom et al.

1.4 Mathematical models of cadmium accumulation in kidney 

Accumulation of cadmium in critical organs has important health effects. Accumulation in the kidney cortex is relevant to renal dysfunction. Accumulation in the bone tissue may lead to demineralization and weakening of the skeleton and a subsequent increased risk of fractures. Mathematical models describing quantitative relationships between cadmium exposure by various routes, accumulation in the kidney, and excretion, have been developed.

No such models have been published describing the accumulation of cadmium in bone. These models have been employed for the calculation of the biological half-life of cadmium and as a tool in risk assessment, describing the relationships between exposures by inhalation or ingestion and accumulation in the critical organ and excretion. , 2009 describes the relationship between oral cadmium intake and urinary excretion and the population variability in Toxicokinetics. While one-compartment models can satisfy certain risk assessment applications, including predicting doses that correspond to kidney cadmium levels below the threshold of toxicity, they do not capture the complex realities of cadmium bio kinetics needed to predict dose-response relationships below and above organ thresholds. , 2003 for estimating daily cadmium intake, giving rise to specified critical concentrations or mass fractions of cadmium in the kidney cortex of population groups in the USA. This model was also used by the CDC in USA to derive Minimal Risk Levels for oral exposure to cadmium. Such calculations are dependent on the accuracy of the estimated relationships between blood cadmium, urine cadmium, and kidney cortex cadmium over the range of exposure scenarios. This model has been used to predict the relationship between cadmium intake by oral or inhalation routes and cadmium concentrations in kidney cortex and urine.

For dietary exposures, the model predicts that the cadmium concentration in kidney cortex reaches its maximum at approximately 55–60 years of age. Women are the most vulnerable section of the population for cadmium-induced effects on kidney tubules. This value is reached after 55 years of dietary exposure to 1.6 μg of cadmium per kg of body mass per day. A cadmium concentration in the kidney cortex of 84 μg g−1 the estimated lower confidence limit on the renal cortex concentration associated with a 10 % probability of low molecular mass proteinuria, corresponds to 1.4nmol mmol-1 creatinine of urinary cadmium.

The same mass fraction in kidney cortex is reached at age 55 years at a constant oral intake of cadmium of 1 μg per kg body mass per day from birth. Assuming a background oral intake of 0.3 μg kg−1 body mass per day, inhalation of 2.7 μg m−3 of an aerosol of cadmium sulfide with a uniform particle size of 1 μm, 8 h per day, 5 days per week, will give rise to a kidney cortex mass fraction of 84 μg g−1, if inhalation occurs from industrial air from age 20–60. For the same inhalation exposure scenario, exposure to 5.1 μg m−3 cadmium oxide will give rise to a kidney cortex mass fraction of 84 μg g−1. , 2009 , the average oral cadmium intake corresponding to a urinary cadmium/creatinine ratio of 2 nmol mmol−1 is 1.6 μg kg−1 body mass, i. Data from healthy subjects with known kidney cadmium levels have been reported by Akerstrom et al. A problem in mathematical modeling is that existing models do not mechanistically simulate dose dependencies of cadmium clearance that arise from cadmium-induced damage to the kidney, which may occur far below mass fractions of cadmium in the kidney cortex of μg g−1. This was the concentration previously believed to be the critical concentration in the kidney cortex in the 10 % most susceptible individuals in a population.