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S9800-01-34-ATTACHMENT C T8 CCR§1532 Cadmium-Appendix A
<br /> Some studies indicate that such proteinuria may be progressive;levels of lie-M observed in the
<br /> urine increase with time even after cadmium exposure has ceased. See,for example, Elinder et al.,
<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 /> r. 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 /> Ltesticular 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 /> CdB is conventionally used to monitor for recent exposure to cadmium. In addition, levels of
<br /> ` CdU and CdB 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(lie-M),a low molecular weight protein.Excess 132-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 Lie-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 B2-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 µg Cd/gram creatinine in urine and 5 µg 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 BZ-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 /> ►� Linden UST SI and Removal,Task Order No.34 Caltrans Contract 06A1895,EFIS 10-1300-0181-0
<br /> Geocon Project No,59800-0134 Page C-4 of 6 September 2014
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