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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 2 C3 to C8 Aliphatic Saturated Aldehydes Shannon D. Langford, Ph.D. Toxicology Group Habitability and Environmental Factors Division Johnson Space Center National Aeronautics and Space Administration Houston, Texas BACKGROUND Spacecraft maximum allowable concentrations (SMACs) of C3 to C8 straight-chain, aliphatic aldehydes have been established and were documented in Volume 4 of Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants (James 2000). These aldehydes, shown in Table 2-1 with their associated physical properties, can enter habitable compartments of spacecraft and contaminate breathing air by several routes, including incomplete oxidation of alcohols in the environmental control and life support system air revitalization subsystem, as a by-product of human metabolism, through materials off-gassing, and during food preparation. These aldehydes have been detected in the atmosphere of manned space vehicles in the past. The National Aeronautics and Space Administration (NASA) analyzed air samples from the crew cabin of the Russian Mir Space Station and found that C3 to C8 aldehyde concentrations peaked at approximately 0.1 milligram per cubic meter (mg/m3) (James 2000, unpublished NASA technical data from 1995). NASA has reviewed most existing reports pertaining to aliphatic aldehyde toxicity in support of establishing the SMACs published in 2000. This report is intended to be a companion document to complement and update James (2000) on C3 to C8 saturated aliphatic aldehyde SMACs. This update summarizes the approach taken in developing the existing SMACs, identifies recent data that may affect existing SMAC values, and establishes and provides rationale for a new 1,000-day SMAC. REVIEW OF EXISTING SMACs AND SUMMARY OF ORIGINAL APPROACH The initial review in 2000 resulted in establishment of 1- and 24-h as well
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 as 7-, 30-, and 180-day SMACs for the C3 to C8 straight-chain, aliphatic aldehydes. Table 2-2 presents the SMACs NASA established for these compounds. Respiratory irritation potential threshold data from rats and mice indicate similar properties (sensory irritation) within this group of compounds and the closely related acetaldehydes (Sim and Pattle 1957; Steinhagen and Barrow 1984; Babiuk et al. 1985). Because the C3 to C8 aldehydes exhibited similar toxicities for this particular end point, the Committee on Spacecraft Exposure Guidelines chose to establish SMACs for these compounds as a group instead of setting a separate SMAC for each compound. The toxicological end points of concern identified previously include mucosal irritation, nasal-cavity injury, nausea and vomiting, and liver damage. SMACs for each exposure time were selected based on the most conservative acceptable concentration (AC) for each toxicological end point. Protection Against Mucosal Irritation An early study reported that exposure to propanal at 134 parts per million (ppm) for 30 min was mildly irritating to mucosal surfaces in humans (Sim and Pattle 1957). The same study found that exposure to 230 ppm butanal and 207 ppm isobutanal for 30 min was not irritating to human subjects. Human data were available only for the three aldehydes propanal, butanal, and isobutanal. However, animal data available at the time indicated the possibility that other aldehydes in the group may be two to three times more irritating than propanal (Salem and Cullumbine 1960; Abdo et al. 1998). Thus, ACs for the 1- and 24-h SMACs based on mucosal irritation were set at 50 ppm (Equation 1). TABLE 2-1 Physical Properties of C3 to C8 Straight-Chain Aliphatic Aldehydes Name Propanal Butanal Pentanal Hexanal Heptanal Octanal CH3(CH2)nCHO: n = 1 n = 2 n = 3 n = 4 n = 5 n = 6 CAS no.: 123-38-6 123-72-8 110-62-3 66-25-1 111-71-7 124-13-0 Molecular weight: 58.1 72.1 86.1 100.2 114.2 128.2 Boiling point (°C): 49 76 103 128 154 171 Melting point (°C): −81 −99 −92 −56 −45 N/A Vapor pressure (mmHg): 687 92 50 10 3 N/A (At °C): 45 20 25 20 25 N/A Conversion factorsa 1 ppm = 2.3 mg/m3 2.9 3.5 4.1 4.6 5.2 1 mg/m3 = 0.422 ppm 0.340 0.284 0.245 0.215 0.191 a1 ppm converted to mg/m3, and 1 mg/m3 converted to ppm. Abbreviations: CAS, Chemical Abstracts Service; N/A, not available; ppm, parts per million; mg/m3, milligrams per cubic meter.
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 TABLE 2-2 SMACs for C3 to C8 Aliphatic Saturated Aldehydes from James (2000) Duration Ppm mg/m3 Toxic End Point to Avoid 1 h 50 125-250a Mucosal irritation 24 h 50 125-250 Mucosal irritation 7 d 6 15-30 Liver injury, mucosal irritation 30 d 1.5 4-8 Liver injury 180 d 1.5 4-8 Liver injury aValue depends on molecular weight of the aldehyde. Source: James 2000, P. 52. (1) where LOAEL is lowest-observed-adverse-effect level. Although short-term ACs were established conservatively to protect against mucosal irritation, some risk of this toxicological end point is allowed. However, for exposure durations exceeding 24 h, mucosal irritation should be precluded. Therefore, the NASA 7-, 30-, and 180-d SMACs based on mucosal irritation were established by dividing the human-derived mildly irritating concentration of 134 ppm for propanal (Sim and Pattle 1957) by 10, yielding an AC of 13 ppm (James 2000) (Equation 2). (2) Protection Against Nasal-Cavity Injury Long-term studies of isobutanal exposure in rats and mice were used to estimate ACs protective for injury to the nasal cavity (squamous metaplasia and olfactory epithelial degeneration in the nose) (Abdo et al. 1998). In the first study of this report, an isobutanal vapor cumulative exposure time of 390 h (6 h/d, 5 d/wk for up to 13 wk) resulted in a no-observed-adverse-effect level (NOAEL) of 500 ppm in rats and mice. Similarly, 500 ppm was reported as the LOAEL in female rats. In the second study from this report, the cumulative exposure time to isobutanal vapor was 3,120 h (6 h/d, 5 d/wk for 2 y). NASA ACs protective of nasal-cavity injury based on the NOAEL and LOAEL values from Abdo et al. (1998) are shown in Equations 3, 4, 5: (3) (4)
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 (5) Protection Against Liver Injury ACs protective against possible liver injury from accumulation of organic acids from aldehyde metabolism were conservatively set at 6.4 ppm (7-d AC) and 1.5 ppm (30- and 180-d AC) (James 2000). The choice of liver injury as a presumptive toxicological end point was based on the observation of vacuoles within hepatocytes of rats exposed six times to 1,300 ppm propanal for 6 h each exposure (Gage 1970). To derive the ACs, NASA used, as a point of departure, the 90-ppm exposure level reported by Gage (20 exposures of 6 h each) to yield no observable liver changes (cumulative exposure of 120 h). It was assumed that harmful metabolites would not accumulate in liver cells below a threshold exposure concentration. Extrapolations to adjust for exposure duration based on application of Haber’s rule would correct the AC to a level below this threshold concentration. The resulting NASA ACs protective for liver injury are shown in Equations 6 and 7: (6) (7) As reviewed previously, the toxicities of the C3 to C8 aliphatic saturated aldehydes appear to be similar (James 2000). Upon review of the AC established for each toxicological end point, group SMACs were established for toxic effects by selecting the acceptable concentration for the most active compound for that end point. Table 2-3 presents the individual ACs for each toxicological end point of concern. SUMMARY OF NEW RELEVANT DATA FROM LITERATURE No toxicity studies (including those examining relevant routes of pulmonary exposure) since 2000 with a bearing on C3 to C8 aliphatic saturated aldehydes SMACs were located during this assessment. ADDITIONAL CONSIDERATION OF NONTOXIC ODOR THRESHOLD The group of C3 to C8 aliphatic saturated aldehydes have different odors, described as agreeably fruity to choking and suffocating (Furia and Bellanca 1975; Furia 1980; U.S. Coast Guard 1985; NFPA 1986; NIOSH 1994). The re-
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 ported odor threshold for one aldehyde in this group, pentanal (the only member of the group for which an odor threshold value is available), is 0.028 ppm (Amoore and Hautala 1983). Table 2-4 summarizes reported odor characteristics for the C3 to C8 aliphatic saturated aldehydes. Odor thresholds—the lowest concentration of a chemical in the air that people can smell—are imprecise measurements. Humans exhibit a wide sensitivity to odors, which can be further affected by factors such as illness. Because odor threshold detection can vary, the concentrations are often reported as ranges. Odor threshold values are not absolute points but rather an average of the sampled populations’ response. In addition, “fruity,” “choking,” and “suffocating” are descriptions of smells individuals have reported. In the case of many chemicals, continued exposure to a chemical odor can also affect detection of the odor. Olfactory adaptation is a very common phenomenon that results from continued exposure to an odor and is characterized by a reduction or loss in smell sensitivity to a particular chemical (Pryor et al. 1970). The lowest concentration of a chemical causing acute stinging, burning sensations, or tear generation in the nose and eyes is reported as the irritation threshold value. These values are distinctly different from odor thresholds and usually require higher ambient chemical concentrations to elicit an irritation response compared with detection of odor (Amoore and Hautala 1983). Acetaldehyde, although not included in the group of C3 to C8 aldehydes, exhibits human irritancy similar to that of pentanal and propanal. As with propanal, human subjects exposed for 30 min to 134 ppm acetaldehyde reportedly experienced slight irritation (Sim and Pattle 1957). Acetaldehyde has a pungent suffocating odor with an odor threshold of 0.05 ppm and a threshold limit value of 25 ppm, very similar to values for propanal and pentanal (Amoore and Hautala 1983; EPA 1987; ACGIH 1999). Amoore and Hautala (1983) reported an irritation threshold of 2,200 ppm for the nose and an ocular level of 11,000 ppm for acet- TABLE 2-3 Acceptable Concentrations for Identified Toxicological End Points, 2000 End Point Uncertainty Factors Acceptable Concentration (ppm) NOAEL Time Species Space flight 1 h 24 h 7 d 30 d 180 d Mucosal Irritation 2-3 1 1 1 50 50 — — — 10 1 1 1 — — 13 13 13 Nasal-cavity injury 1 HR 10 1 — — 50 27 — 3 HR 10 1 — — — — 12 Liver injury 1 HRthreshold 10 1 — — 6 1.5 1.5 SMACsa 50 50 6 1.5 1.5 aSMACs for each exposure time are selected based on the most conservative AC for each toxicological end point. Abbreviation: HR, Haber’s rule.
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 TABLE 2-4 Selected Odor Characteristics of C3 to C8 Aliphatic Saturated Aldehydes Compound Odor Odor Threshold Reference Propanal Suffocating, fruity, similar to acetaldehyde, pungent, unpleasant, choking Not available Furia and Bellanca 1975; Furia 1980; USCG 1985; NFPA 1986 Butanal Pungent, aldehyde Not available Lewis 1997 Pentanal Powerful, acrid, pungent, strong 0.028 ppm Amoore and Hautala 1983; NIOSH 1994 Hexanal Fruity, strong green grass, sharp aldehyde Not available Furia and Bellanca 1975; Furia 1980; Lewis 1997 Heptanal Fatty pungent, penetrating fruity Not available Furia 1980; Budavari 1989 Octanal Sharp fatty, fruity Not available Furia and Bellanca 1975 Abbreviations: NFPA, National Fire Protection Association; NIOSH, National Institute for Occupational Safety and Health; USCG, U.S. Coast Guard. aldehyde—approximately 44,000 times higher (nose) than the odor threshold value for this compound. Amoore and Hautala (1983) classified both acetaldehyde and pentanal as “Class A” substances, which can serve as bellwether indicators because their odor threshold values are much lower than their threshold limit values. The low odor threshold of pentanal (and, by inference, the other C3 to C8 aldehydes) could serve as a means to alert spacecraft crew to the presence of a substance at levels far lower than would be expected to cause toxicological effects. Granted, crew could experience smell aversion as a result of exposure to noxious chemical smells. Although such aversion could impede crew performance, it should not be categorized as a toxic effect. Therefore, odor threshold values are not used here as a toxicological end point. The odor threshold for pentanal (0.028 ppm) is several times higher than the lowest SMAC values for the C3 to C8 aldehydes (about 143 times higher). Therefore, it is understood that the SMAC levels, which are designed to protect against adverse health effects, will not necessarily prevent spacecraft crew from experiencing smell aversion due to noxious odors. REVISION OF EXISTING SMACs AND ESTABLISHMENT OF 1,000-DAY SMAC After review of the studies considered in setting the original SMACs in 2000, the Committee on Spacecraft Exposure Guidelines decided to revise all the ACs for the C3 to C8 aldehydes.
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 The uncertainty factor of 2 to 3 originally applied to the acute 1- and 24-h SMAC in 2000 will be revised to a factor of 3. A factor of 3 is considered the most conservative for this group of aldehydes and reflects animal data suggesting that some members of this group of compounds are two to three times more irritating than the base compound—propanal (Salem and Cullumbine 1960; Abdo et al. 1998). The 1- and 24-h ACs remain based on the point of departure of 134 ppm (mildly irritating to mucosal surfaces after 30 min of exposure in humans) (Sim and Pattle 1957). Therefore, the revised 1- and 24-h C3 to C8 aldehyde SMACs based on mucosal irritation are set at 45 ppm (Equation 8). (8) The 2006 Committee revisited the original rationale used in setting the 7-through 180-d SMACs in 2000. In 2000, the long-term SMACs were predicated on protecting against liver pathology, which was based on acute (5-d) exposure data from rats (Gage 1970). The study reported by Gage used discontinuous exposures to propanal. The 2000 SMACs then used a factor to correct for continuous versus discontinuous exposure conditions. No additional factors were applied to account for differences in the duration of exposure (5 d to 7, 30, or 180 d) based on the assumption that a threshold dose, below which no liver pathology would occur, had been established. However, upon reevaluation, the acute exposure protocol and the now questioned relationship between cellular vacuoles and liver pathology eliminated use of the NOAEL reported by Gage as a point of departure for the longer-term SMACs. The Committee chose instead to select the study of Abdo et al. (1998). This study design more closely corresponds to exposure durations bounded by the longer-term SMACs (7 through 1,000 d). In addition, the end point (squamous metaplasia of respiratory epithelium) was believed to be more toxicologically appropriate and defensible. Abdo et al. used exposure of rats and mice to select concentrations of isobutanal vapor for 6 h/d, 5 d/wk, for up to 13 wk or 2 y. The 13-wk study revealed a NOAEL of 500 ppm in both rats and mice, whereas the 2-y study revealed a LOAEL of 500 ppm in female rats. The LOAEL of 500 ppm reported for female rats exposed for 2 y was selected as the point of departure for the 7-through 1,000-day SMACs. A factor of 10 was applied to extrapolate from a LOAEL to a NOAEL. A correction factor of 3 was applied to account for interspecies differences in response. Finally, a factor of 3 was applied, as was the case for the new 1- and 24-h ACs (discussed previously), to reflect animal data suggesting differences in irritating potential for these aldehydes (Salem and Cullumbine 1960; Abdo et al. 1998). The revised 7-, 30-, and 180-d and the new 1,000-d SMACs based on nasal-cavity injury are set at 5 ppm (Equation 9). (9)
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 The 2008 SMACs for C3 to C8 aliphatic saturated aldehydes are presented in Table 2-5. DIFFERENCES BETWEEN ORIGINAL AND CURRENT APPROACH OF THE NATIONAL RESEARCH COUNCIL COMMITTEE ON TOXICOLOGY The National Research Council (NRC) Committee on Toxicology, as well as other regulatory bodies, is primarily interested in using benchmark dose modeling (BMD) to interpret toxicological data, as BMD modeling is favored over traditional threshold dose (NOAEL, LOAEL) methods, since it allows for greater use of the available data. The NRC recommends that BMD methods be used when sufficient and appropriate dose-response data are available (NRC 2000). However, the NOAEL/LOAEL-based method is recommended by the NRC in the absence of sufficient data or when special considerations are warranted. The original SMACs for C3 to C8 straight-chain, aliphatic aldehydes were established based on a LOAEL/NOAEL and uncertainty factor method. BMD methodology was applied to data from the long-term SMAC (7- through 1,000-d) study of Abdo et al. (1998). The BMD analysis is summarized below. Background for BMD Analysis of Long-Term Exposure Data Isobutyraldehyde was administered to male and female F344/N rats and to B6C3F1 mice by inhalation (6 h/d, 5 d/wk) for up to 13 wk or 2 y (Abdo et al. 1998). These results were used to the calculate benchmark concentration (BMC) for various toxic effects. Uncertainty factors were applied to the lower 95% confidence limit of the benchmark concentration (BMCL) to arrive at maximum allowable concentrations. These values are compared with the proposed current SMACs. TABLE 2-5 SMACs for C3 to C8 Aliphatic Saturated Aldehydes, 2008 Duration ppm mg/m3 Toxic End Point to Avoid 1 h 45 113 Mucosal irritation 24 h 45 113 Mucosal irritation 7 d 5 11.8 Nasal-cavity injury 30 d 5 11.8 Nasal-cavity injury 180 d 5 11.8 Nasal-cavity injury 1,000 d 5 11.8 Nasal-cavity injury Note: A representative average odor threshold concentration for the C3 to C8 aliphatic saturated aldehydes is 0.028 ppm (pentanal) (Amoore and Hautala 1983). Some aldehydes in this group exhibit strong noxious odors detectable by humans at levels well below SMAC levels for these compounds.
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 13-Week Exposures Reported by Abdo et al. 1998 Ten animals per group were exposed to 0, 500, 1,000, 2,000, 4,000, and 8,000 ppm of isobutyraldehyde. All rats died at 8,000 ppm and three male and six female rats died at 4,000 ppm. All mice died at 8,000 ppm, and all except one mouse, a male, died at 4,000 ppm. Body weight gains were reduced at 4,000 ppm in both sexes of rats and at 1,000 ppm in both sexes of mice. Several end points could not be ascertained at 8,000 ppm. Hence, data from the 8,000-ppm group were not used for estimating low-dose BMCs. Incidence rates for the most sensitive end point for each sex of rats and mice are listed in Table 2-6. Because the multistage model can describe a wide variety of dose-response shapes, it was used to estimate the dose-response relationships. BMCs and BMCLs associated with an excess risk of 10% (BMC10 and BMCL10) are listed in Table 2-6. Using the BMCL10 as a point of departure for establishing a maximum allowable concentration is generally more conservative (stringent) than using the NOAEL. Consistent with the calculation of SMACs, an uncertainty factor of 10 was used for interspecies extrapolation; no uncertainty factor was used for intraspecies variability or a potential risk at the point of departure (NOAEL or BMCL). Further, adjustment for the duration of exposure used Haber’s rule, which assumes equal toxic effects for equal cumulative exposures. Hence, experimental exposures of 6 h/d for 5 d/wk are assumed to be equivalent to continuous exposures of (6/24) × (5 / 7) = 0.18 times the exposure administered over the (13 × 7) = 91 d. The most sensitive end point, lowest BMCL10 = 340 ppm, occurred for serous exudate in male mice (Table 2-6). This results in a 30-d SMAC of and a 180-d SMAC of These results are complementary to the proposed SMAC of 5 ppm, which is based on a LOAEL/NOAEL method. Further, average severity scores were examined by using a polynomial model with the dose-response data procedure for continuous data in the EPA Benchmark Dose Software program. The most sensitive end point for severity was for olfactory epithelium degeneration in male rats. The benchmark response corresponding to an average severity grade of 1 (minimal effect) produced a BMCL of 1,110 ppm, which exceeds the minimum BMCL of 340 ppm obtained for the incidences of effects.
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 TABLE 2-6 Incidence of Effects in the Most Sensitive End Point in Each Sex of Rats and Mice (10 Animals per Dose Group) and Estimates of BMC10 and BMCL10 for 13-wk Exposures Species/Sex End Point Exposure (ppm) BMC (ppm) BMCL (ppm) 0 500 1,000 2,000 4,000 Rat (male) Olfactory epithelium degeneration 0 0 0 10 10 880 680 Rat (female) Suppurative inflammation 2 6 2 0 10 2,030 1,000 Mice (male) Serous exudate 0 2 0 4 10 1,000 340 Mice (female) Serous exudate 0 0 0 3 10 1,480 1,020 Two-Year Exposures Reported by Abdo et al. 1998 Initially, 50 animals per group were exposed to 0, 500, 1,000, and 2,000 ppm of isobutyraldehyde. Incidence rates for the most sensitive end point for each sex of rats and mice are listed in Table 2-7. Because the multistage model can describe a wide variety of dose-response shapes, it was used to estimate the dose-response relationships. BMCs and BMCLs associated with an excess risk of 5% (BMC5 and BMCL5) are listed in Table 2-7. With 50 animals per group, at least 5 animals (10%) with an effect are required to achieve a statistically significant increase (P ≤ 0.05) above a background of 0 of 50 animals with the effect. However, using the BMCL5 rather than the BMCL10 as a point of departure for establishing a maximum allowable concentration is generally more conservative (stringent) than using the NOAEL. Consistent with the calculation of SMACs, an uncertainty factor of 10 was used for interspecies extrapolation; no uncertainty factor was used for intraspecies variability or a potential risk at the point of departure (NOAEL or BMCL). Further, adjustment for the duration of exposure used Haber’s rule, which assumes equal toxic effects for equal cumulative exposures. Hence, experimental exposures of 6 h/d for 5 d/wk are adjusted by the factor (6/24) × (5/7) for equivalency to continuous exposure. The most sensitive end point (lowest BMCL5 = 150 ppm) occurred for respiratory epithelium squamous metaplasia in female rats (Table 2-7). Presumably, a 2-y lifetime exposure in rodents would be adequate to provide protection for a 1,000-d exposure to humans. The resulting 1,000-d SMAC is
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 TABLE 2-7 Incidence of Effects and Estimates of BMC5 and BMCL5 for 2-y Exposures Species/Sex End Point Exposure (ppm) BMC (ppm) BMCL (ppm) 0 500 1,000 2,000 Respiratory epithelium squamous metaplasia Rat (male) 1/50a 1/49 10/49 44/50 590 450 Rat (female) 1/49 11/50 9/49 44/50 270 150 Olfactory epithelium degeneration Mice (male) 0/50 0/50 11/50 45/50 580 480 Mice (female) 1/50 1/50 27/50 49/50 440 320 aObserved/total. These results again are indistinguishable from (within a factor of 2) the proposed SMAC of 5 ppm, which is based on a LOAEL/NOAEL method. Further, average severity scores were examined by using a polynomial model with the dose-response data procedure for continuous data in the EPA Benchmark Dose Software program. The most sensitive end point for severity was for olfactory epithelium degeneration in female mice. The benchmark response corresponding to an average severity grade of 1 (minimal effect) produced a BMCL of 1,420 ppm, which exceeds the minimum BMCL of 150 ppm obtained for the incidences of effects. Therefore, the lower BMCL value (for incidence rather than severity) will be used to develop a proposed SMAC. Summary of Conclusions from BMD Analyses Results from the 13-wk exposures to isobutyraldehyde were used to calculate 30- and 180-d SMACs. The most sensitive end point was the incidence of serous exudate in male mice, leading to 30- and 180-d SMACs of 18.4 and 3.1 ppm, respectively. The most sensitive end point from the 2-y exposures was the incidence of respiratory epithelium squamous metaplasia in female rats producing a 1,000-d SMAC of 2.7 ppm. The proposed 7- to 1,000-d SMAC of 5 ppm, derived via application of a LOAEL/NOAEL method should provide protection for the effects observed in the study by Abdo et al. (1998). COMPARISON WITH OTHER AIR-QUALITY LIMITS Exposure guidelines for a limited subset of C3 to C8 aliphatic saturated aldehydes exist with various public health and occupational health entities as well as with industry and government advisory bodies. Table 2-8 lists of some of these guidelines and regulatory standards for comparison with the current and proposed NASA SMACs.
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 TABLE 2-8 Selected Inhalation Exposure Levels for Selected C3 to C8 Aliphatic Saturated Aldehydes Compound Organization/Reference Exposure Guideline Exposure Level Propanal ACGIH 2004 TLV (8 h TWA) 20 ppm Pentanal ACGIH 2005 TLV (8 h TWA) 50 ppm Pentanal NIOSH 2005 REL (10 h TWA) 50 ppm Butanal AIHA 2003 WEEL (8 h TWA) 25 ppm C3 to C8 aliphatic aldehydes NASAa SMAC (1 h and 24 h) 45 ppm aOnly 1- and 24-h SMACs are listed here for comparison with similar exposure duration guidelines from other organizations. Abbreviations: ACGIH, American Conference of Governmental Industrial Hygienists; AIHA, American Industrial Hygiene Association; NIOSH, National Institute for Occupational Safety and Health; REL, recommended exposure limit; TLV, threshold limit value; TWA, time-weighted average; WEEL, workplace environmental exposure level. The current NASA 1- and 24-h SMACs are very similar to exposure levels from other organizations at comparable exposure durations. Exposure limits and guidelines for pentanal (for which values are available for comparison) have remained stable for several years. No guidelines are available for long-term exposure durations to compare with the 7-, 30-, 180-, and 1,000-d SMACs. RECOMMENDATIONS FOR ADDITIONAL RESEARCH Shortcomings in the toxicity database pertaining to C3 to C8 aliphatic saturated aldehydes persist. Lack of data on the effects of acute (humans) and chronic (humans and animals) exposures as well as lack of data elucidating the nonlethal exposure effects to animals confounds attempts to establish exposure guidelines. Recommendations for additional research pertaining to toxicity of this group of aldehydes are unchanged from those proposed by James (2000). Increasing the number of exposure concentrations used as well as expanding the end point measurements examined for all aldehydes in this group would be most beneficial. The long-term exposure guidelines established here are designed to protect against nasal epithelial squamous metaplasia. Long-term pulmonary studies would be beneficial in confirming and extending the work of Gage (1970) and validating the protective assumptions made in establishing our intermediate and long-term SMACs. REFERENCES Abdo, K.M., J.K. Haseman, and A. Nyska. 1998. Isobutyraldehyde administered by inhalation (whole body exposure) for up to 13 weeks or 2 years was a respiratory tract
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 toxicant but was not carcinogenic in F344/N rats and B6C3F1 mice. Toxicol. Sci. 42(2):136-151. ACGIH (American Conference of Governmental Industrial Hygienists). 1999. TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents, Biological Exposure Indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. ACGIH (American Conference of Governmental Industrial Hygienists). 2004. TLVs and BEIs: Based on the Documentation of the Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. ACGIH (American Conference of Governmental Industrial Hygienists). 2005. TLVs and BEIs: Based on the Documentation of the Threshold Limit Values for Chemical Substances and Physical Agents & Biological Exposure Indices. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. AIHA (American Industrial Hygiene Association). 2003. The AIHA Emergency Response Planning Guidelines and Workplace Environmental Exposure Levels Guide Handbook. Fairfax, VA: American Industrial Hygiene Association. Amoore, J.E., and E. Hautala. 1983. Odor as an aid to chemical safety: Odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air water dilution. J. Appl. Toxicol. 3(6):272-290. Babiuk, C., W.H. Steinhagen, and C.S. Barrow. 1985. Sensory irritation response to inhaled aldehydes after formaldehyde pretreatment. Toxicol. Appl. Pharmacol. 79(1):143-149. Budavari, S., ed. 1989. The Merck Index—Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc. EPA (U.S. Environmental Protection Agency). 1987. Health Assessment Document for Acetaldehyde. EPA/600/8-86-015A. Environmental Criteria and Assessment Office, Office of Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC. Furia, T.E., ed. 1980. CRC Handbook of Food Additives, Vol. 2, 2nd Ed. Boca Raton, FL: CRC Press. Furia, T.E., and N. Bellanca. 1975. Fenaroli’s Handbook of Flavor Ingredients, Vol. 2, 2nd Ed. Cleveland, OH: The Chemical Rubber Co. Gage, J.C. 1970. The subacute inhalation toxicity of 109 industrial chemicals. Br. J. Ind. Med. 27(1):1-18. James, T.J. 2000. C3 to C8 aliphatic saturated aldehydes. Pp. 42-59 in Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Vol. 4. Washington, DC: National Academy Press. Lewis, R.J., Sr., ed. 1997. Hawley’s Condensed Chemical Dictionary, 13th Ed. New York, NY: John Wiley & Sons. NFPA (National Fire Protection Association). 1986. Fire Protection Guide on Hazardous Materials, 9th Ed. Boston, MA: National Fire Protection Association. NIOSH (National Institute for Occupational Safety and Health). 1994. NIOSH Pocket Guide to Chemical Hazards. NIOSH Publication No. 94-116. Washington, DC: U.S. Government Printing Office. NIOSH (National Institute for Occupational Safety and Health). 2005. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) No. 2005-151. Cincinnati, OH: National Institute for Occupational Safety and Health, Center for Disease Control and Prevention, U.S. Department of Health and Human Services.
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Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants, Volume 5 NRC (National Research Council). 2000. Methods for Developing Spacecraft Water Exposure Guidelines. Washington, DC: National Academy Press. Pryor, G.T., G. Steinmetz, and H. Stone. 1970. Changes in absolute detection threshold and in subjective intensity of supra-threshold stimuli during olfactory adaptation and recovery. Percept. Psychophys. 8:331-335. Salem, H., and H. Cullumbine. 1960. Inhalation toxicities of some aldehydes. Toxicol. Appl. Pharmacol. 2:183-187. Sim, V.M., and R.E. Pattle. 1957. Effect of possible smog irritants on human subjects. J. Am. Med. Assoc. 165(15):1908-1913. Steinhagen, W.H., and C.S. Barrow. 1984. Sensory irritation structure-activity study of inhaled aldehydes in B6C3F1 and Swiss-Webster mice. Toxicol. Appl. Pharmacol. 72(3):495-503. USCG (U.S. Coast Guard). 1985. CHRIS—Hazardous Chemical Data, Vol. II. Washington, DC: U.S. Government Printing Office.