he metal were smelted resulting in the highest potential off-site airconcentrations.
As the smelting of other metals will release particulates in proportion to the total amount of materialsmelted and the dispersion of those metals will follow the same dispersion patterns as nickel, itfollows that the off-site concentrations of other metal particulates will be proportional to the amountof metal smelted. Based on the relative toxicities of the various metals and the amounts of eachmetal smelted, off-site concentrations of all metals smelted at PGDP are below levels of healthconcern.
ATSDR considered interactive effects (cumulative, additive, synergistic, and antagonistic) ofsubstances following exposure to multiple substances to the extent of scientific knowledge in thisarea.
- Cumulative effects (the effects associated with concurrent exposure by all relevant pathwaysand routes of exposure to a group of substances that share a common mechanism of toxicity) were addressed on pages 91 and 92 and in Table 24 of the PHA.
- Additive effects (the combined effects of two substances is equal to the sum of the effects ofeach agent given alone) were considered for exposure to radioactive materials on pages 117through 119 in the PHA. Of the metals evaluated in this appendix only nickel and monel areconsidered to have additive effects (because monel is a nickel alloy). However, the amountof monel smelted and emitted is insignificant with regard to the amount of nickel smelted.
- Existing information is inconclusive with regard to potential synergistic effects (when thecombined effect of two substances is much greater than the sum of the effect of each agent given alone) for the metals evaluated in this appendix.
- Antagonistic effects (when a substance reduces the toxicity or uptake of another substance)were not considered in this appendix in order to maintain a health-protective screeningscenario even though concurrent exposures to magnesium or zinc reduce the toxicity ofnickel.
ATSDR has reviewed the scientific literature surrounding chemical interactions and noted that if theestimated exposure doses for individual contaminants detected at the site are below doses shown tocause adverse effects (No Observed Adverse Effect Level; NOAEL), then ATSDR considers that thecombined effect of multiple chemicals is not expected to result in adverse health effects. It should benoted that typical environmental exposure doses to both carcinogenic and non-carcinogenicchemicals are more than 1,000 times lower than laboratory-induced effect threshold doses. Thisapproach to chemical interactions is based on the results of numerous studies:
- Several animal and human studies [15,16,17,18] have reported thresholds for interactions. Studies have shown that exposure to a mixture of chemicals is unlikely to produce adversehealth effects as long as components of that mixture are detected at levels below the NOAEL for individual compounds [19,20].
- The absence of interactions at doses 10-fold or more below effect thresholds have beendemonstrated [21,22]. Specifically, in two separate subacute toxicity studies in rats [23,24], adverse effects disappeared altogether as the dose was decreased to below the threshold level.
- For carcinogens, the interactions are more difficult to quantify due to the large study size(humans or animals) needed for statistical significance at the low doses observed inenvironmental exposures . In an animal study, Takayama et al. (1989) reported that 40substances tested in combination at 1/50 of their cancer effect level (CEL) resulted in anincrease in cancer . However, Hasegawa et al. (1994) reported no increase in cancerwhen dosing animals at 1/100 of the CEL for 10 compounds .
Estimated maximum hourly and annual nickel concentrations in areas of potential off-site exposuredo not exceed health-based cancer and non-cancer comparison values for either acute or chronicexposures (WKWMA workers and residents; respectively). As the toxicity of other smelted metals islower than nickel and/or the quantity of metals smelted is much lower