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S9200-06-82 ATTACHMENT D T8 CCR goL07. Cadmium-Appendix A
<br /> 1985. Such observations, however, are not universal, and it has been suggested that studies in
<br /> which proteinuria has not been observed to progress may not have tracked patients for a
<br /> sufficiently long time interval (Jarup, Ex. 8-661).
<br /> When cadmium exposure continues after the onset of proteinuria, chronic nephrotoxicity may
<br /> occur(Friberg, Ex. 29). Uremia results from the inability of the glomerulus to adequately filter
<br /> blood. This leads to severe disturbance of electrolyte concentrations and may lead to various
<br /> clinical complications including kidney stones(L-140-50).
<br /> After prolonged exposure to cadmium, glomerular proteinuria, glucosuria, aminoaciduria,
<br /> phosphaturia, and hypercalciuria may develop(Exs. 8-86,4-28, 14-18). Phosphate, calcium,
<br /> glucose, and amino acids are essential to life,and under normal conditions,their excretion should
<br /> be regulated by the kidney. Once low molecular weight proteinuria has developed,these elements
<br /> dissipate from the human body. Loss of glomerular function may also occur, manifested by
<br /> decreased glomerular filtration rate and increased serum creatinine. Severe cadmium- induced
<br /> renal damage may eventually develop into chronic renal failure and uremia(Ex. 55).
<br /> Studies in which animals are chronically exposed to cadmium confirm the renal effects observed
<br /> in humans(Friberg et al., 1986). Animal studies also confirm problems with calcium metabolism
<br /> and related skeletal effects which have been observed among humans exposed to cadmium in
<br /> addition to the renal effects. Other effects commonly reported in chronic animal studies include
<br /> anemia, changes in liver morphology, immunosuppression and hypertension. Some of these
<br /> effects may be associated with co-factors. Hypertension, for example, appears to be associated
<br /> with diet as well as cadmium exposure. Animals injected with cadmium have also shown
<br /> testicular necrosis(Ex. 8-86B).
<br /> 2. Biological Markers
<br /> It is universally recognized that the best measures of cadmium exposures and its effects are
<br /> measurements of cadmium in biological fluids, especially urine and blood. Of the two, CdU is
<br /> conventionally used to determine body burden of cadmium in workers without kidney disease.
<br /> Cd13 is conventionally used to monitor for recent exposure to cadmium. In addition, levels of
<br /> CdU and Cd13 historically have been used to predict the percent of the population likely to
<br /> develop kidney disease (Thun et al., Ex. L-140-50; WHO, Ex. 8-674; ACGIH, Exs. 8-667, 140-
<br /> 50).
<br /> The third biological parameter upon which OSHA relies for medical surveillance is Beta-2-
<br /> microglobulin in urine 02-M), a low molecular weight protein. Excess 82-M has been widely
<br /> accepted by physicians and scientists as a reliable indicator of functional damage to the proximal
<br /> tubule of the kidney (Exs. 8-447, 144-3-C,4-47, L-140-45, 19-43-A).
<br /> Excess B2-M is found when the proximal tubules can no longer reabsorb this protein in a normal
<br /> manner. This failure of the proximal tubules is an early stage of a kind of kidney disease that
<br /> commonly occurs among workers with excessive cadmium exposure. Used in conjunction with
<br /> biological test results indicating abnormal levels of CdU and CdB,the finding of excess a2-M can
<br /> establish for an examining physician that any existing kidney disease is probably cadmium-
<br /> related (Trs. 6/6/90, pp. 82- 86, 122, 134). The upper limits of normal levels for cadmium in urine
<br /> and cadmium in blood are 3 [tg Cd/gram creatinine in urine and 5 gg Cd/liter whole blood,
<br /> respectively. These levels were derived from broad-based population studies.
<br /> Three issues confront the physicians in the use of 82-M as a marker of kidney dysfunction and
<br /> material impairment. First, there are a few other causes of elevated levels of 132-M not related to
<br /> cadmium exposures, some of which may be rather common diseases and some of which are
<br /> serious diseases (e.g.,myeloma or transient flu, Exs. 29 and 8-086). These can be medically
<br /> evaluated as alternative causes(Friberg, Ex. 29). Also,there are other factors that can cause B2-M
<br /> to degrade so that low levels would result in workers with tubular dysfunction. For example,
<br /> Stockton 6-Lane,Task Order No.82 Caltrans Contract 06A1141,EA 10-03A1001
<br /> Project No.S9200-06-82 Page D-4 of 6 December 2009
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