Supporting Documentation for MassDEP Air Guidelines - Allowable Ambient Limits

CADMIUM (and Cadmium Compounds)
CASRN: 7440-43-9
Update: December 4, 2013 /
Cd
Massachusetts Guideline Limits[1]:
AAL = 0.0002 ug/m3 (annual average concentration)
TEL = 0.002 ug/m3 (24 hour average concentration)
Chemical Properties: (HSDB 2011)
Odor characteristics: / Odorless
Odor threshold: / Not applicable
Irritant: / Yes, to nose and throat
Sensitizer: / No information
Chemical class: / Metal
Boiling Point: / 765 oC
Melting Point: / 321 oC
Vapor pressure: / 1 Pa at 257 oC
Unit Conversion factor: / Not applicable
Critical Effects[2]:
·  Kidney effects (proteinuria) and decreased lung function in occupationally exposed humans.
·  Target organ systems affected include kidney and respiratory system.
·  Known human carcinogen.
Potentially Susceptible Populations:
·  Children and elderly because effects are associated with cumulative exposure.
·  People with kidney disease or a compromised respiratory system.
TEL Basis for Criteria:
Available chronic inhalation noncancer toxicity values:
REL 0.02 ug/m3 (CalEPA 2008, derived 12/2000)
MRL 0.01 ug/m3 (ATSDR 2012)
The MRL of 0.01 ug/m3 derived by ATSDR was selected as the basis of the TEL. A relative source contribution factor of 0.2 was applied to derive the TEL.
TEL = 0.01 ug/m3 x 0.2 (RSC) = 0.002 ug/m3
The ATSDR MRL and CalEPA REL are within a factor of 3 from each other, thus the newer value from ATSDR was selected based on the updating method (MassDEP 2011). In addition, the MRL was derived using several newer environmental exposure studies (instead of a single occupational study that is the basis of the CalEPA value), improved measures of internal dose, and a more sensitive measure of response.
The MRL is based on a meta-analysis of studies evaluating the relationship between urinary cadmium concentration and elevated biomarkers of renal function in men and women environmentally exposed to cadmium (ATSDR 2012). Dose response modeling of the study data from eleven individual study populations conducted in Europe (n=4), Japan (n=4) and China (n=3) provided estimates of the urinary cadmium concentration that was associated with a 10% excess risk of low molecular weight proteinuria. The three European studies (Buchet et al. 1990; Suwazono et al. 2006; Jarup et al. 2000) provided the lowest estimates of urinary cadmium dose (UCD) associated with a 10% excess risk of proteinuria, mean 1.34 ug Cd/g creatinine (0.50, 2.18 95% confidence interval). The value associated with 95% lower confidence interval of the urinary cadmium concentration associated with 10% excess risk of proteinuria (UCDL10), 0.5 ug Cd/g creatinine, was selected as the point of departure for the MRL (ATSDR 2012).
The UCDL10 of 0.5 ug Cd/g creatinine was transformed into an estimate of the air concentration of cadmium (expressed as ug/m3) that would result in the UCDL10 at age 55 (approximate age of peak cadmium concentration in the renal cortex associated with a chronic intake) (ATSDR 2012). ATSDR used models of deposition and clearance of particles (ICRP 1994) and pharmacokinetics (Kjellstrom-Nordberg 1978) to simulate the airborne concentration of cadmium oxide or cadmium sulfide that would result in a urinary cadmium level of 0.5 ug/g creatinine assuming air was the only source of exposure. Because diet is a significant contributor to cadmium exposure, thus body burden, ATSDR (2012) used the mean of the male and female age-weighted average dietary intakes of cadmium in nonsmoking males and females in the US estimated by Choudhury et al. (2001), 0.3 ug Cd/kg/day, to estimate cadmium intake from sources other than air.
The point of departure for the inhalation MRL, UCDL10ADJ of 0.01 ug/m3, was derived from the model assuming a dietary intake of 0.3 Cd ug/kg/day and a target level for urinary cadmium of 0.5 ug/g creatinine (ATSDR 2012).
The UCDL10 ADJ in air was divided by a composite uncertainty factor of 10.
MRL = 0.1 ug/m3 = 0.01 ug/m3
3 x 3
Uncertainty factors:
UFA (extrapolation from animals to humans) = 1
UFH (human population variability in response) = 3
UFS (subchronic to chronic extrapolation) = 1
Modifying factor = 3
The MRL is based on studies evaluating humans. A value of 3 was used for the uncertainty factor UFH, to account for possible increased sensitivity of diabetics (ATSDR 2012). A modifying factor of 3 was used to account for the lack of human data that could be used to compare the relative sensitivity of the respiratory tract and kidneys (ATSDR) 2012.
The CalEPA REL (2008) is within a factor of two of the MRL even though it was derived from humans exposed occupationally and used a different method for extrapolation. CalEPA (2008) calculated alternative RELs using the LOAEL observed in men exposed for more than 20 years from the Lauwerys et al. (1974) study, and from points of departure from alternative studies. These alternative analyses provide estimates similar to the REL selected by CalEPA, and the MRL selected by ATSDR.
Cancer Classification:
USEPA (1992): B1 probable human carcinogen.
IARC (2009): Group 1, carcinogenic to humans.
NTP (2005): Known to be human carcinogen.
NTEL Basis for Cancer Assessment:
Estimates of cancer unit risks are available from USEPA and CalEPA.
1.8x10-3 per ug/m3 finalized 1986 (USEPA 1992)
4.2x10-3 per ug/m3 finalized 1986; revised 1990)(CalEPA 2009)
The UR of 4.2x10-3 per ug/m3 derived by CalEPA (2009) was selected as the basis of the NTEL.
NTEL = 1 x 10-6 / 4.2x10-3 per ug/m3 = 0.000238 ug/m3, rounded to 0.0002 ug/m3.
The two available estimates of cancer potency are within a factor of 3 (2.3) of each other, and based on the same study of lung cancer deaths in workers exposed to cadmium (Thun et al. 1985). The difference in the values is attributable to the models used to estimate the unit risks and methods used to estimate background risk of lung cancer mortality.
The UR from CalEPA (2009) was selected as the basis of the NTEL because CalEPA quantitatively included the impact of workers having a lower rate of death from lung cancer than the general population (healthy worker effect) in their UR estimate.
The URs are based on increased lung cancer mortality in a cohort of 602 white males working at a cadmium smelter for a minimum of 6 months during the years 1940-1969 (Thun et al. 1985). Workers were followed to the end of 1978. Exposure was estimated from individual work histories and industrial hygiene measurements and included consideration of use of respiratory protection. CalEPA (2009) evaluated and set aside the potential for confounding from smoking and exposure to arsenic.
References:
ATSDR (Agency for Toxic Substances and Disease Registry). 2012. Toxicological profile for cadmium. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.
CalEPA (California Environmental Protection Agency). 2008. Chronic Toxicity Summary Cadmium and Cadmium Compounds, December 2000. Technical Support Document For the Derivation of Noncancer Reference Exposure Levels, Appendix D3. Air Toxics Hot Spots Risk Assessment Guidelines.
CalEPA (California Environmental Protection Agency). 2009. Air Toxics Hot Spots Risk Assessment Guidelines Part II: Technical Support Document for Cancer Potency Factors. California Environmental Protection Agency, Office of Environmental Health Hazard Assessment (OEHHA).
Choudhury H, Harvey T, Thayer WC, Lockwood TF, Stiteler WM, Goodrum PE, Hassett JM, Diamond GL. 2001. Urinary cadmium elimination as a biomarker of exposure for evaluating a cadmium dietary exposure-biokinetics model. J Toxicol Environ Health A 63(5):321-350 (as cited in ATSDR 2012).
HSDB (Hazardous Substances Data Base). 2011. Available: http://toxnet.nlm.nih.gov (Accessed April 29, 2011).
IARC (International Agency for Research on Cancer). 2012. Arsenic, metals, fibres and dust, Volume 100C. A review of human carcinogens. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Lyon, France.
ICRP (International Commission on Radiological Protection). 1980. Metabolic data for cadmium. Limits for intakes of radionuclides by workers. Pergamon Press, NY: International Commission on Radiological Protection, 42-44. ICRP Publication No. 30, Part 2 (as cited in ATSDR 2012).
Kjellström T, Nordberg GF. 1978. A kinetic model of cadmium metabolism in the human being. Environ Res 16:248-269 (as cited in ATSDR 2012).
Lauwerys RR, Buchet JP, Roels HA, Brouwers J Stanescu D. 1974. Epidemiological survey of workers exposed to cadmium. Arch Environ Health 28:145-148 (as cited in CalEPA 2008).
MassDEP (Massachusetts Department of Environmental Protection). 2011. Methodology for Updating Air Guidelines: Allowable Ambient Limits (AALs) and Threshold Effects Exposure Limits (TELs). Office of Research and Standards.
NTP (National Toxicology Program). 2005. Report on Carcinogens, Eleventh Edition; U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program.
Thun M, Schnorr T, Smith A, Halperin W, Lemen R. 1985. Mortality among a cohort of U.S. cadmium production workers—an update. J Natl Cancer Inst 74:325-333 (as cited in CalEPA 2008).
USEPA (U.S. Environmental Protection Agency). 1992. Integrated Risk Information System (IRIS). Available: http://www.epa.gov/iris/ (accessed April 29, 2011).
Revision History:
TEL/AAL first listed – 1985
TEL/AAL updated and summary added 12/2013

Massachusetts Department of Environmental Protection

Office of Research and Standards

Cadmium 1

[1] The process used for selecting and deriving Threshold Effects Exposure Limits (TELs), Non-Threshold Effects Exposure Limits (NTELs) and Allowable Ambient Limits (AALs) is described in MassDEP (2011).

[2] This summary document provides information about the toxicity data supporting the available toxicity values for this chemical and the rationale for selecting among values. It is not intended to be a comprehensive summary of all toxicity information for this chemical.