Interim Report #4 on Spacecraft Water Exposure Guidelines (2000)

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EXECUTIVE SUMMARY 1 INTERIM REPORT #4 ON SPACECRAFT WATER EXPOSURE GUIDELINES 2000 EXECUTIVE SUMMARY This report was prepared by the Subcommittee on Spacecraft Water Exposure Guidelines of the National Research Council’s Committee on Toxicology in response to a request from the National Aeronautics and Space Administration (NASA) for an independent review of spacecraft water exposure guidelines (SWEGs) for selected water contaminants. SWEGs are established for exposures of 1, 10, 100, and 1000 days. The 1-day SWEG is intended to prevent irreversible harm and degradation in crew performance during rare emergency conditions lasting for periods up to 24 hours. Temporary discomfort (e.g., mild skin or eye irritation) may occur as long as there is no effect on judgment, performance, or ability to respond to an emergency. Longer-term SWEGs are intended to prevent adverse health effects (either immediate or delayed) and degradation in crew performance that could result from continuous exposure in closed spacecraft for as long as 1000 days. In contrast to the 1-day SWEG, longer-term SWEGs are intended to provide guidance for exposure under what is expected to be normal operating conditions in spacecraft. Guidelines for developing SWEGs have been established by the subcommittee (NRC 2000a), and NASA uses those guidelines to develop SWEGs for individual water contaminants. The guidance document also provides background information on the contaminants found in spacecraft water and a discussion of ranking contaminants for review priority. NASA is responsible for selecting the water contaminants for which SWEGs will be established. To ensure that the SWEGs are developed in accordance with the guidelines, NASA requested that this National Research Council subcommittee independently review the draft SWEGs documents. In performing the review, the subcommittee reviews the documents as many times as necessary until it is satisfied that the SWEGs are scientifically justified. Once the subcommittee makes this determination, the final documents are included as appendices in a subsequent published report. This interim report provides an evaluation of eight SWEGs documents drafted by NASA. The subcommittee reviewed NASA’s draft documents on eight chemical contaminants: manganese, 2- mercaptobenzothiazole, silver, zinc and its salts, barium and its salts, nickel, di(2-ethylhexyl) phthalate, and di-n- butyl phthalate. It concluded that three of the SWEGs documents are ready to be finalized (silver, zinc, and di-n- butyl phthalate) and that the other documents need to be revised by NASA and then re-evaluated by the subcommittee. The key findings and recommendations of the subcommittee are summarized below. Manganese • Because several of the key toxicity studies on manganese involve the use of bolus dosing (gavage) rather than continuous dosing (feed or water), a reasonable estimate is needed of the amount of manganese that is absorbed from feed or water compared to that absorbed after gavage. NASA should compare the available data on the absorption of manganese following the various oral dosing methods to determine whether the difference in absorption can be quantified and used in its derivation of the acceptable concentrations (ACs) for manganese. 

EXECUTIVE SUMMARY 2 • NASA should expand the rationale for its calculations of the ACs for manganese by — critically analyzing the available epidemiology studies of populations exposed to manganese in drinking water, and using that analysis to determine whether the data can be used to derive an AC; — providing a better analysis of the finding of sperm head abnormalities in rats; — considering clastogenicity data as a possible basis for calculating an AC; and — presenting its attempts to calculate ACs using the benchmark dose (BMD) approach. 2-Mercaptobenzothiazole (MBT) • A better assessment of the contact sensitization potential of 2-mercaptobenzothiazole is needed. • NASA should evaluate the nephrotoxicity data reported in rats exposed to MBT in an NTP (1988) study to determine whether an AC should be calculated on the basis of that data. • NASA needs to strengthen its rationale for not using tumorigenicity data to calculate an AC for MBT by discussing the lack of dose-response observed in animals studies and the results of epidemiology studies of workers exposed to MBT. Silver • The subcommittee recommends that NASA’s SWEGs document on silver is ready to be finalized once NASA has clarified a few remaining issues regarding the absorption of silver in rodents and humans. Zinc and Its Salts • NASA needs to re-evaluate and make adjustments to several of its AC calculations for zinc. NASA should — reconsider its decision to use an uncertainty factor lower than 10 to extrapolate from a LOAEL to a NOAEL when the selected end point is considered to be an insignificant health effect; and — analyze the relevance and significance of the finding of decreased superoxide dismutase in humans exposed to zinc; the available data can be handled in a variety of ways to determine an AC on the basis of that end point, and NASA should evaluate all of the possible options before making a decision. Barium and Its Salts • NASA should re-evaluate how it determined some of its ACs for barium by — considering whether clinical oral doses of barium should be used to derive a 1-day AC; — not using hypertension as an end point for calculating ACs for barium; 

EXECUTIVE SUMMARY 3 — investigating whether proteinuria observed in rats is a significant finding that has implications for human health; and — using the BMD approach to derive a 100-day AC using neurotoxicity data and a 1000-day AC using renal nephropathy data. Nickel • Further consideration is needed of whether the ACs for nickel should include an adjustment to account for its known contact sensitization. Di(2-ethylhexyl) Phthalate (DEHP) • NASA should recalculate all of the ACs it derived for DEHP using the BMD approach, because the BMDL01 rather than the BMD01 should be used in the calculations. • NASA should apply the BMD approach to data on Sertoli cell vacuolization and on aspermiogenesis. Di-n-butyl Phthalate (DBP) • The subcommittee concludes that NASA’s SWEGs document on DBP is ready to be finalized once NASA has corrected the AC calculations that used a BMD. The BMDL01 rather than the BMD01 should be used in the calculations.