TOXICITY AND RELATED DATA ON ZINC CADMIUM SULFIDE
PHYSICAL AND CHEMICAL PROPERTIES
ZINC CADMIUM SULFIDE (ZnCdS) (CAS NO. 68583-45-9) was manufactured originally by the New Jersey Zinc Company and later by the U.S. Radium Corporation in New Jersey. The ZnCdS used in the Army studies appeared as a yellow or green (depending on whether copper or silver was used as an activator), somewhat fluffy powder under visible light. It was composed of about 80% zinc sulfide, ZnS, and 20% cadmium sulfide, CdS; the concentration of copper or silver in ZnCdS was about 0.005%. Magnesium silicate or some other silicate was added at 12% to facilitate the dispersion of ZnCdS. ZnCdS is not just a physical mixture of the two compounds; its constituents—ZnS and CdS—are sintered by heating a mixture of the 2 compounds to about 900°C (Ruda 1992) so that a crystalline lattice structure containing zinc, cadmium, and sulfur is formed. The sintered compound reportedly does not contain pure ZnS or CdS, because the sintering process is highly efficient (Sheila Fabiano, USR Optonix, Inc., personal commun., May 27, 1995).
Zinc sulfide exists in two crystalline forms: a cubic form with the zincblende structure (the most common form in nature, occurring as the rather common mineral sphalerite) and a hexagonal form, which is sometimes referred to as the wurtzite structure (Fedorov and others 1993). The cubic form forms at lower temperatures than the hexagonal. The hexagonal form is stable at formation temperatures above 1026°C. Both forms have tetrahedral coordination about both the zinc and sulfur atoms, with each sulfur atom tetrahedrally bonded to four zinc atoms and each zinc atom tetrahedrally bonded to four sulfur atoms. Figure 3-1 shows diagrams of both forms. Cadmium sulfide exists primarily in the hexagonal (wurtzite) form and occurs in nature as the very rare mineral greenockite. Solid solutions of ZnS and CdS can exist in either crystal form, depending on the composition, sintering temperature, and cooling rate. At the composition used in the Army's studies (80% ZnS and 20% CdS), the transition between wurtzite and zincblende occurs at about 500°C. However, rapid quenching of the material from the reported 900°C sintering temperature would preserve the wurtzite form.
ZnCdS is a fluorescent material and fluoresces brilliantly under ultraviolet light chiefly in the region from 3100 Å to 4000 Å.
The density of ZnCdS is 4.0 g/cm3 (Leighton and others 1965). A gram of ZnCdS contains some 1010 particles. It can be made in the form of particles small enough to meet the criteria for studying atmospheric diffusion, and the dispersibility of ZnCdS is high enough to enable its practical use in the Army's dispersion tests (Leighton 1955). ZnCdS used in the Army's tests had a mass median aerodynamic diameter of 2-3 µm, and the particle diameter ranged from 0.5 to 6.25 µm.
ZnCdS is stable in the atmosphere long enough to conduct the tracer experiment (hours to days). It is insoluble in water and only weakly soluble in strong acids, but it is soluble in oxidizing acids, such as concentrated nitric acid. ZnCdS continues to fluoresce after 2 h of exposure to air at 450°C. When immersed in 12 M hydrochloric acid, it is not completely destroyed until after some 8 h (Leighton 1955). ZnCdS is insoluble in lipids.
TOXICOKINETICS AND BIOAVAILABILITY OF ZNCDS: AVAILABILITY OF CADMIUM FROM ZNCDS
No studies on the toxicokinetics of ZnCdS were found. ZnCdS is insoluble in water and lipids and poorly soluble in strong acids. A small number of toxicity studies (which do not meet the current standards of toxicity testing) have suggested that it is not absorbed through the skin or gastrointestinal tract (Lawson and Alt 1965; Leighton and others 1965). The subcommittee believes that the lack of solubility of ZnCdS particles together with the limited toxicity studies implies that it will not be absorbed through the skin or gastrointestinal tract and that inhaled particles are not likely to be absorbed from the lung into blood for systemic distribution. Its lack of solubility also suggests that it is highly unlikely that free cadmium ions would become bioavailable to target organs as a result of inhalation of ZnCdS, However, information is not available on whether ZnCdS might break down in the respiratory tract into more-soluble components, which could be easily absorbed into the body.
The subcommittee reviewed all available toxicity data on ZnCdS from the Army's files and from the open literature. The toxicity database on ZnCdS is limited and consists of eye irritation and dermal toxicity studies, single-dose oral toxicity studies, and observations reported in a few exposed to high concentrations of the dust for 1-2 years. These data are summarized below.
Eye irritation from exposure to a phosphor mixture that consisted of 65.4% liquid cosmetic base (composition not specified) and 34.6% (≈35%) ZnCdS (Lawson and Alt 1965; Leighton and others 1965) was examined by instilling 0.1 mL of the test mixture in the eyes of adult rabbits and then observing them at 24, 48, and 72 h. The results of the experiment indicated that ZnCdS has negligible eye-irritation properties (Lawson and Alt 1965).
Dermal toxicity resulting from exposure to ZnCdS was examined by applying the test mixture at 9.4 g/kg of body weight to 4 rabbits for 24 h.
The mixture was injected under a rubber sleeve fitted around the clipped trunks of the test animals. No toxic effects were noted, and there was no evidence of dermal irritation during the 3 wk of observation after the treatment (Leighton and others 1965).
Lawson (1966) and Lawson and Alt (1965) reported on the medical use of ZnCdS for skin painting as a diagnostic tool for cancer. The compound is a phosphor whose fluorescence increases with increases in temperature. The authors used material that was composed of 59% CdS and 41% ZnS with less than 0.05% silver, less than 0.0005% nickel, and traces of halide to detect the higher temperature of blood in veins that leave a cancerous area. The phosphor was mixed into the same water-soluble cosmetic base used in the Army's toxicity studies and painted on the skin over the area of concern. A warm subcutaneous vein leaving a cancer could be clearly displayed by exposing the painted skin to UV light and observing the fluorescence of the phosphor. The authors stated that the ZnCdS phosphor was ''sufficiently insoluble to be physiologically inert.''
The only oral studies conducted by the Army were single-dose toxicity experiments in which rats and dogs were fed the mixture. None of the animals died at the highest doses tested, which were 10 g/kg of body weight and 20 g/kg of body weight for dogs and rats, respectively. These tests therefore indicated that the LD50 of the mixture—the dose that is lethal to 50% of the exposed animals—for dogs and rats was greater than 10 g/kg of body weight and 20 g/kg of body weight, respectively. Because the phosphor mixture used in the LD50 study contained 65.4% liquid cosmetic base and about 35% ZnCdS, the highest dose of the mixture tested in dogs and rats contained ZnCdS at 3.5 and 7.0 g/kg of body weight, respectively. To avoid physical injury from the administration of massive doses, higher doses were not administered to the animals. Thus it appears from these data that ZnCdS is not acutely toxic when given orally; that finding is consistent with the insolubility of the compound and its suspected lack of bioavailability.
No toxicity experiments of inhaled ZnCdS are available in the literature.
Because the ZnCdS particles used in the Army's dispersion studies were so small, the particles could probably be inhaled and deposited in the deep lung. The lack of solubility of the particles suggests that they are not likely to be absorbed from the lung into the blood for systemic distribution.
No information is available on the potential toxicity of the particles in the lung. It is also not known whether ZnCdS can be broken down by pulmonary macrophages into more-soluble forms of cadmium.
The Arkansas Department of Health evaluated the possible adverse effects of ZnCdS aerosol exposure from the Army's tests in White County, Arkansas (White 1977). The tests consisted of 131 releases of ZnCdS in 1967-1968. The evaluation was based on examining 4 workers who disseminated the chemical and were exposed to high concentrations of the dust for 1-2 yr, and examining data from the Arkansas Cancer Registry for any increases in incidence of lung, renal, or prostatic cancer from 1970 to 1975. There was no indication of cadmium-induced illness either in the 4 workers or in the general population. However, it should be noted that the followup period was not long enough to detect chronic effects, such as cancer. No studies examining the chronic toxicity, including cancer, of ZnCdS were found.
IMPLICATIONS OF VARIABLE COMPOSITION
The Army asked that the National Research Council assess the toxicologic implications of the variable composition of ZnCdS used in the Army's tests. The subcommittee has reviewed the available information on the composition of ZnCdS used in the Army's tests and found no evidence of substantial variation in the amounts of zinc and cadmium in the sintered compound. Any slight differences in composition should be reflected by equally small changes in potential toxicity.
CONCLUSIONS AND RECOMMENDATIONS
Data on the toxicity of ZnCdS are sparse. Results of feeding studies conducted in dogs and rats suggest that ZnCdS is practically nontoxic in acute (single, high-dose) exposures. ZnCdS was not found to be a skin or eye irritant in rabbits.
The physical and chemical properties of ZnCdS are fairly well understood. It is soluble only in strong acids and probably not absorbed
through the skin or gastrointestinal tract. Its lack of solubility suggests that it is highly unlikely that free cadmium ions would become bioavailable as a result of inhalation of ZnCdS; however, information is not available on whether ZnCdS might break down in the respiratory tract into more-soluble components, which could easily be absorbed into the blood. This information and the limited toxicity data available suggests that ZnCdS is not likely to show systemic toxicity.
The subcommittee in its interim report (NRC 1995) recommended that the Army conduct studies to determine the bioavailability and inhalation toxicity of ZnCdS in experimental animals. This research will strengthen the database needed for assessing the risks of ZnCdS and lessen the need to rely on the use of a surrogate for toxicity information. The Army has begun the research recommended by the subcommittee, and the results are expected shortly. The subcommittee recommends that when the results of the research become available, they be reviewed by experts outside the Army to determine whether the subcommittee's conclusions are still valid or should be modified.