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S9200-06-82 ATTACHMENT D T8 CCR§oz07. Cadmium -Appendix A regarding the degradation of 132-M, workers with acidic urine(pH<6)might have b2-M levels that are within the "normal" range when in fact kidney dysfunction has occurred(Ex. L-140-1) and the low molecular weight proteins are degraded in acid urine. Thus, it is very important that the pH of urine be measured,that urine samples be buffered as necessary (See Appendix F.),and that urine samples be handled correctly, i.e., measure the pH of freshly voided urine samples,then if necessary, buffer to pH> 6(or above for shipping purposes), measure pH again and then, perhaps, freeze the sample for storage and shipping. (See also Appendix F.) Second,there is debate over the pathological significance of proteinuria, however, most world experts believe that 132-M levels greater than 300 pg/g Cr are abnormal (Elinder, Ex. 55, Friberg, Ex. 29). Such levels signify kidney dysfunction that constitutes material impairment of health. Finally, detection of B2- M at low levels has often been considered difficult, however, many laboratories have the capability of detecting excess 132-M using simple kits, such as the Phadebas Delphia test,that are accurate to levels of 100 µg B2-M/9 Cr U(Ex. L-140-1). Specific recommendations for ways to measure B2-M and proper handling of urine samples to prevent degradation of 132-M have been addressed by OSHA in Appendix F, in the section on laboratory standardization. All biological samples must be analyzed in a laboratory that is proficient in the analysis of that particular analyte, under paragraph(1)(1)(iv). [See Appendix F]. Specifically, under paragraph(1)(1)(iv),the employer is to assure that the collecting and handling of biological samples of cadmium in urine (CdU),cadmium in blood(CdB), and beta-2 microglobulin in urine(132-M)taken from employees is collected in a manner that assures reliability. The employer must also assure that analysis of biological samples of cadmium in urine (CdU),cadmium in blood(CdB), and beta-2 microglobulin in urine (132-M)taken from employees is performed in laboratories with demonstrated proficiency for that particular analyte. (See Appendix F.) 3. Lung and Prostrate Cancer The primary sites for cadmium-associated cancer appear to be the lung and the prostate(L-140- 50). Evidence for an association between cancer and cadmium exposure derives from both epidemiological studies and animal experiments. Mortality from prostrate cancer associated with cadmium is slightly elevated in several industrial cohorts,but the number of cases is small and there is not clear dose-response relationship. More substantive evidence exists for lung cancer. The major epidemiological study of lung cancer was conducted by Thun et al., (Ex. 4-68). Adequate data on cadmium exposures were available to allow evaluation of dose-response relationships between cadmium exposure and lung cancer. A statistically significant excess of lung cancer attributed to cadmium exposure was observed in this study even when confounding variables such as co-exposure to arsenic and smoking habits were taken into consideration(Ex. L- 140-50). The primary evidence for quantifying a link between lung cancer and cadmium exposure from animal studies derives from two rat bioassay studies; one by Takenaka et al., (1983),which is a study of cadmium chloride and a second study by Oldiges and Glaser(1990)of four cadmium compounds. Based on the above cited studies,the U.S. Environmental Protection Agency (EPA)classified cadmium as "B1", a probable human carcinogen, in 1985 (Ex. 4-4). The International Agency for Research on Cancer(IARC) in 1987 also recommended that cadmium be listed as "2A", a probable human carcinogen (Ex. 4- 15). The American Conference of Governmental Industrial Hygienists (ACGIH) has recently recommended that cadmium be labeled as a carcinogen. Since 1984,NIOSH has concluded that cadmium is possibly a human carcinogen and has recommended that exposures be controlled to the lowest level feasible. 4. Non-carcinogenic Effects Stockton 6-Lane,Task Order No.82 Caltrans Contract 06A1141,EA 10-03A1001 Project No.S9200-06-82 Page D-5 of 6 December 2009