Spacecraft Water Exposure Guidelines for Selected Contaminants Volume 2 (2007) / Chapter Skim
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Appendix 11 Zinc and Zinc Salts (Inorganic)
Appendix 11 Zinc and Zinc Salts (Inorganic)
Pages 465-514
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From page 465... ...
TABLE 11-1 Chemical and Physical Properties of Zinc and a Few Zinc Compoundsa Zinc Sulfate Chemical Zinc Zinc Chloride Heptahydrate Zinc Oxide Zinc Acetate Formula Zn ZnCl2 ZnSO47H2O ZnO Zn(C2H3O2) 2 Molecular 66.38 136.29 287.54 81.4 183.46 weight % of zinc 100% 47.97% 40.5% 80.34% 35.64% Water Insoluble 4.32 g/mL at 1.66 g/mL Insoluble 0.43 g/mL solubility 25 ºC a Data from Merck Index 1989.
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From page 466... ...
This document will be limited to addressing the adverse effects of extraneous zinc that may leach into the drinking water through the water processing system (from distribution lines) , the humidity condensate heat exchangers (through corrosion)
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From page 467... ...
. A similar phenomenon of changes in fractional zinc absorption in response to changes in the dietary zinc concentrations have been described by several investigators (Wada et al.
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It is generally believed that zinc absorption is homeostatically controlled by the zinc content in the intestine and by circulating zinc (Davies 1980; Cousins 1985)
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. The range of normal plasma zinc concentrations is 85-110 g per deciliter (dL)
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. Rats receiving zinc as ZnCl2, ZnSO4, zinc phosphate, or zinc citrate at 2.65 mg/kg/d over a 4-d period excreted 87-98% of the intake.
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. Excess copper in the diet inhibits zinc absorption from a zinc-sufficient diet, but the effect is relatively minor compared to the effect of excess zinc on copper status (O'Dell 1989)
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. In vivo, it has been documented that oral administration of zinc to sickle cell anemia patients reduced the number of irreversible sickle cells (Brewer 1979)
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. A vast amount of data pertaining to zinc toxicity is available, and a significant portion of the data is from human case reports and human subject experiments, mainly from zincsupplementation studies.
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In animals, zinc deficiency increased plasma 11-hydroxy steroids, and excess zinc decreased the same steroids (Quarterman and Humphries 1979)
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In addition, a significant decrease in acid phosphatase in the femoral epiphysis was seen in the zinc-treated group. The result that zinc causes a decrease in bone calcium may be very important because it indicates that zinc may trigger bone resorption.
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The National Research Council (NRC) committee on spacecraft water exposure guidelines (SWEGs)
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(1982) , eight healthy adult women per group ingested zinc acetate as a dietary supplement at 0, 15, 50, or 100 mg/d for a dose of 0.45, 1.03, or 1.86 mg/kg/d (plus daily dietary zinc intake at 0.2 mg/kg)
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From page 478... ...
No effect of zinc supplementation on circulating concentrations of leukocytes or lymphocyte subsets or on copper status could be observed. It must be noted that markers of immune status such as phagocytic activity of neutrophils and blastogenic response of cell types to T cells were not measured in this study.
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. Dietary zinc supplementation did not affect plasma insulin and glucose concentrations.
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. A subchronic study was carried out with young female SpragueDawley rats by administering zinc acetate in their drinking water at 0, 47.5, 95, or 190 mg/kg body weight for 3 mo (Llobet et al.
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Similar signs of copper deficiency, including decreased concentrations of plasma ceruloplasmin, were also seen in sickle cell anemia patients given zinc supplements at 150-200 mg/d for 2 y (Prasad et al.
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From page 482... ...
a diet containing zinc carbonate (zinc at 5,000 μg/g diet; the estimated dose was 175 mg/kg/d) for 22 wk resulted in statistically significant differences in blood hemoglobin (13.55 ± 0.125 g/100 mL in controls and 11.51 ± 0.24 mg/100 mL in the treated group)
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From page 483... ...
They fed 3-wk-old male Sprague-Dawley rats (n = 10) experimental diets containing zinc as ZnCl2 at 500 mg/kg/d for 8 wk and observed abnormal structure of the caudal epididymal sperm chromatin.
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From page 484... ...
because the effects were not seen in mice fed a standard calcium diet. Also, in rats exposed to zinc chlorate at 17.5 mg/kg/d in drinking water, sister chromatid exchanges were observed in the bone marrow (Kowalska-Wochana et al.
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Carcinogenicity No human data are available that relate cancer to zinc administered orally as zinc supplements or otherwise. When rats were provided with ZnCl2 in their drinking water at 450 ppm (zinc at 13.4 mg/kg/d)
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(1997) reported a significant decrease in zinc concentrations in weight-bearing and non-weight-bearing bones of growing rats after 14 d in space.
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acetate (zinc 30 mg/d wk leukocytes or lymphocyte subsets; 2003a, b Chelazome no effect on putative indices of copper status Drinking water; dose = 18 d Pregnant rats Increased resorption of fetuses Kumar 1976 ZnSO4 150 (unspecified strain)
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From page 488... ...
ZnSO4 1980 Zinc carbonate Drinking water; dose = 5 wk Sprague Dawley Decrease in hemoglobin, hematocrit, Smith and Larsen 500 rat MCH, and MCHC 1946 Oral; dose = 4.4 6 wk Human, male Reduced HDL cholesterol, elevated Chandra 1984 ZnSO4 serum LDL cholesterol; impaired immune status Supplement, 3/d; dose = 6 wk Human, male and Decreased ESOD and ceruloplasmin Samman and ZnSO4 2.4 female in females Roberts 1988 Zinc gluconate Gelatin capsules, 2/d; 6 wk Human, male Decreased erythrocyte copper-zinc Fischer et al. total dose = 0.71 superoxide dismutase (affects copper 1984 status)
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Drinking water; dose = 13 wk Mouse, male and Anemia; decreased white blood Maita et al. 1981 ZnSO4 104 and 1,110 female; strain, cells; forestomach ulceration ICR Zinc carbonate Oral dose; dose = 174 22 wk Rabbit, male; New Decreased hemoglobin Bentley and Zealand white concentrations Grubb 1991 rabbits Zinc oleate Drinking water; dose = 52 wk Mouse, sex not Anemia (hemoglobin was 40% of Walters and Roe 68 (dose was changed (total)
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From page 490... ...
of 0.3 mg/kg/d for soluble zinc salts based on a LOAEL of zinc at 59.72 mg/d (corresponding to about 1 mg/kg/d based on the human diet-supplement study)
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In certain cases, zinc supplements have been administered as medical interventions. No epidemiologic study has been done to relate the concentration of zinc in drinking water to any adverse effects.
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Environmental Protection Agency; FDA, Federal Drug and Administration; HA, health advisory; IOM, Institute of Medicine; NAS, Nation Academy of Sciences; NRC, National Research Council; MCL, maximum contaminant level; MCLG, maximum contaminant level goal; MRL, minimal risk level; RDA, Recommended Dietary Allowance; RfD, reference dose; SDWR, secondary drinking water regulation; SMCL, secondary maximum contaminant level (replaced by SDWR) ; SNARL, suggested no adverse response level; UL, tolerable upper intake level.
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The effects may have been transient, and peripheral adverse effects resulting from such changes may have been documented. Therefore, for the 1-d AC derivation, the data that can be extracted from short-term zinc supplementation studies in humans can be used as described in the rest of this section.
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From page 494... ...
, where 0.43 mg/kg/d = NOAEL; 70 kg = nominal body weight; and 2.8 L/d = nominal water consumption. No species or time extrapolation factors are needed.
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÷ (10 × 2.8 L/d) = 11 mg/L, where 4.4 mg/kg/d = LOAEL, 70 kg = nominal body weight; 10 = LOAEL to NOAEL extrapolation factor; and 2.8 L/d = nominal water consumption.
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, and hematocrit, serum ferritin, and copper-zinc ESOD activity were measured at the end of 6 and 10 wk. After 10 wk of supplementation, hematocrit, serum ferritin, and ESOD activity were significantly lower than their pretreatment levels, indicating that iron and copper status can be affected by zinc supplementation.
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, where 0.833 mg/kg/d = LOAEL; 70 = nominal body weight; 3 = LOAEL to NOAEL extrapolation factor; 2.8 L/d = nominal water consumption; 100 d/70 d or 1.43 = time extrapolation factor; and 3 = spaceflight safety factor for anemia (changes in hemoglobin)
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From page 498... ...
) = 3.0 mg/L, where 4.4 mg/kg/d = LOAEL; 70 kg = nominal body weight; 10 = LOAEL to NOAEL extrapolation factor; 2.8 L/d = nominal water consumption; and 100 d/28 d or 3.57 = time extrapolation factor.
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From page 499... ...
Thus, the observed change in serum HDL cholesterol, especially after the relatively short duration of a 100-d zinc supplementation, is not likely to present a significant risk for the development of chronic arteriosclerosis. In addition, a review of data indicated that the direction of the time-response data for the observed changes was not clear.
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(1977) , male and female C3H mice that ingested zinc as ZnSO4 at 70 mg/kg/d in their drinking water ad libitum for 12 mo exhibited hypertrophy and vacuolation of islet cells of the pancreas, hypertrophy of the zona fasciculata of the adrenal cortex, and histopathologic evidence of increased synthetic and secretory activity of adrenals.
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, where 70 mg/kg/d = LOAEL; 70 kg = nominal body weight; 10 = LOAEL to NOAEL extrapolation factor; 10 = species extrapolation factor; 2.8 L/d = nominal water consumption; and 1,000 d/180 d or 5.555 = time extrapolation factor. Bentley and Grubb (1991)
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From page 502... ...
Although the 1,000-d AC is lower than the EPA guideline, given the fact that NASA's 1,000-d AC also incorporates a safety factor that protects against any spaceflightinduced hematologic effects, the value for spacecraft water derived by NASA from animal studies is consistent with that of EPA. A summary of ACs and SWEGs for various durations is listed in Table 11-7.
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1989 Effects on 5 -- NOAEL, Human Bonham 10/ 19 1 1 1 -- -- immunologic status 0.43 et al. and copper status 2003a,b (Continued)
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Species Study NOAEL Species Factor 1 d 10 d 100 d 1,000 d Effects on NOAEL, Human Bonham et 10/ 19 1 1 1 -- -- 5 -- immunologic status 0.43 al. 2003a,b and copper status Hypertrophy of LOAEL, Mouse Aughey et 10 10 5.55 1 -- -- -- 3 adrenal cortex and 70 al.
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From page 505... ...
1977. The effects of oral zinc supplementation in the mouse.
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From page 506... ...
1975. Effect of phytate on zinc absorption and faecal zinc excretion and carcass retention of zinc, iron, copper and manganese.
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1992. Cysteine-rich intestinal protein and intes tinal metallothionein: an inverse relationship as a conceptual model for zinc absorption in rats.
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1969. Relationship of maternal dietary zinc during gestation and lactation to development and zinc, iron and copper content of the postnatal rat.
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1993. Homeostasis of zinc in marginal human zinc deficiency: role of absorption and endogenous excretion of zinc.
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2000. Methods for Developing Spacecraft Water Exposure Guidelines.
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1979. Effect of zinc deficiency and zinc supplementation on adrenals, plasma steroids and thymus in rats.
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1991. Homeostatic regu lation of zinc absorption and endogenous losses in zinc-deprived men.
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1997. Trace element composition and histological analysis of rat bones from the space shuttle.
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