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From page 123... ... Crotonaldehyde, Trans and Cis +Trans APPENDIX C Category Plot for Crotonaldehyde Chemical Toxicity - TSD All Data Crotonaldehyde 100000.0 Human - No Effect Human - Discomfort 10000.0 Human - Disabling 1000.0 Animal - No Effect ppm 100.0 Animal - Discomfort Animal - Disabling 10.0 AEGL-3 Animal - Some Lethality AEGL-2 1.0 Animal - Lethal AEGL-1 0.1 AEGL 0 60 120 180 240 300 360 420 480 Minutes FIGURE 5-1 Prepublication Copy 123 Read the entire page →
From page 124... ... (ppm) with an excess cancer risk of: based on toxicity Exposure 10-4 10-5 10-6 duration endpoints ½ hour 8.9 221 22 2.2 1 hour 4.4 110 11 1.1 4 hours 1.1 28 2.8 0.28 8 hours 0.56 14 1.4 0.14 124 Prepublication Copy Read the entire page →
From page 125... ... AEGL values are applicable to rare events or single, once-in-a-lifetime exposures and the neoplasms resulted from lifetime treatment. Prepublication Copy 125 Read the entire page →
From page 126... ... Uncertainty Factors/Rationale: Total uncertainty factor: 30 Interspecies: 10: The actual exposure concentration and time were not known for the key study and there was a lack of supporting animal studies. 126 Prepublication Copy Read the entire page →
From page 127... ... Similar or higher AEGL-3 values could be obtained with mice, rats, and guinea pigs. Prepublication Copy 127 Read the entire page →
From page 128... ... Minor nonlethal effects such as respiratory tract irritation 1 This document was prepared by AEGL Development Team member Richard Thomas of the National Advisory Committee on Acute Exposure Guideline Levels for Hazardous Substances (NAC) and Robert Young of the Oak Ridge National Laboratory. Read the entire page →
From page 129... ... Prepublication Copy 129 Read the entire page →
From page 130... ... American Industrial Hygiene Association Journal 24: 137-143. 130 Prepublication Copy Read the entire page →
From page 131... ... . Prepublication Copy 131 Read the entire page →
From page 132... ... Additionally, iron pentacarbonyl exhibits a steep exposure-response 132 Prepublication Copy Read the entire page →
From page 133... ... . Stokinger noted that the signs and symptoms of iron pentacarbonyl exposure are similar to those for nickel carbonyl and include giddiness and headache, and occasionally dyspnea and vomiting; these effects being similar to those associated with metal fume fever. Read the entire page →
From page 134... ... Under ambient atmospheric conditions iron pentacarbonyl may undergo photochemical decomposition to iron nonacarbonyl and carbon monoxide, or burn to ferric oxide. TABLE 7-2 Chemical and Physical Data for Iron Pentacarbonyl Synonyms Iron Carbonyl; Pentacarbonyl Iron Reference Common name Iron pentacarbonyl ACGIH 2001; Budavari et al. Read the entire page →
From page 135... ... Gage (1970) reported the results of inhalation studies on groups of four male and four female rats exposed to iron pentacarbonyl. Read the entire page →
From page 136... ... 1959. TABLE 7-4 Mortality in Rats Exposed for Four Hours to Iron Pentacarbonyl Concentration (ppm) Read the entire page →
From page 137... ... TABLE 7-6 Lethal Toxicity of Iron Pentacarbonyl in Mice Exposed for 30 Minutes Exposure Concentration (ppm) Mortality at 3 Days Mortality at 5 Days 470 16/20 20/20 387 15/20 17/20 270 8/20 9/20 204 5/20 5/20 Source: Sunderman et al. Read the entire page →
From page 138... ... Rats Gage (1970) reported the results of inhalation studies on groups of four male and four female rats exposed to iron pentacarbonyl. Read the entire page →
From page 139... ... Data regarding the nonlethal effects of iron pentacarbonyl in animals are limited to data from rat studies showing inconsequential effects (similar to responses observed for control groups) or evidence of pulmonary involvement (congestion and edema) Read the entire page →
From page 140... ... 1959) and that dimercaprol and sodium diethyldithiocarbamate, both of which are effective antidotes for nickel carbonyl, are ineffective for iron pentacarbonyl (Sunderman et al. Read the entire page →
From page 141... ... DATA ANALYSIS FOR AEGL-2 6.1. Summary of Human Data Relevant to AEGL-2 Quantitative data consistent with AEGL-2 level effects in humans following exposure to iron pentacarbonyl are unavailable. Read the entire page →
From page 142... ... a Under ambient atmospheric conditions iron pentacarbonyl may undergo photochemical decomposition to iron nonacarbonyl and carbon monoxide, or burn to ferric oxide if an ignition source is present. 142 Prepublication Copy Read the entire page →
From page 143... ... Rat Data Using EPA Software V 1.3.1 Number of animals dying at 2.91 ppm for 6 hours Benchmark 1 of 10 5 of 10 MLE LC01 2.4 ppm 1.9 ppm BMCL LC05 1.7 ppm 0.80 ppm Sunderman et al., 1959 rat-mouse data Iron pentacarbonyl 100 80 60 % died % dead rats 40 % dead mice 20 0 0 60 120 180 240 300 360 420 480 ppm FIGURE 7-1 Lethal response of rats and mice following 30-minute inhalation exposure to iron pentacarbonyl. Prepublication Copy 143 Read the entire page →
From page 144... ... 0.23 ppm 0.23 ppm 0.18 ppm 0.11 ppm 0.075 ppm a Under ambient atmospheric conditions iron pentacarbonyl may undergo photochemical decomposition to iron nonacarbonyl and carbon monoxide, or burn to ferric oxide if an ignition source is present. 144 Prepublication Copy Read the entire page →
From page 145... ... No other values are currently available. TABLE 7-12 Extant Standards and Guidelines for Iron Pentacarbonyl Exposure Duration Guideline 10-minute 30-minute 1-hour 4-hour 8-hour AEGL-1 NR NR NR NR NR AEGL-2 0.077 ppm 0.077 ppm 0.060 ppm 0.037 ppm 0.025 ppm AEGL-3 0.23 ppm 0.23 ppm 0.18 ppm 0.11 ppm 0.075 ppm ERPG-1 (AIHA) Read the entire page →
From page 146... ... Absence of an AEGL-1 does not imply that exposure below the AEGL-2 is without adverse effects. Under ambient atmospheric conditions iron pentacarbonyl may undergo photochemical decomposition to iron nonacarbonyl and carbon monoxide, or burn to ferric oxide. Read the entire page →
From page 147... ... 1988. An acute inhalation toxicity study of iron pentacarbonyl in the rat. Read the entire page →
From page 148... ... Additionally, the exposure response relationship and apparent extreme toxicity of iron pentacarbonyl following inhalation exposure in animals suggest little margin between exposures with little or no apparent effect and those causing lethality. Therefore, AEGL-1 values are not recommended. Read the entire page →
From page 149... ... Prepublication Copy 149 Read the entire page →
From page 150... ... Additionally, lethality in rats following acute inhalation exposure to iron pentacarbonyl exhibits a steep exposure-response relationship with little margin between minimal and lethal effects, and little individual variability in the response of test animals. 10-min AEGL-3 Due to uncertainties in extrapolating from a 6-hour experimental time point to a 10-minute AEGL-specific duration, the 30-minute AEGL-3 has been adopted as the 10-min AEGL-3. Read the entire page →
From page 151... ... Prepublication Copy 151 Read the entire page →
From page 152... ... Therefore, the value of n was set at unity for the exponential temporal scaling equation, C1 x t = k. 152 Prepublication Copy Read the entire page →
From page 153... ... This approach is consistent with the available data demonstrating a steep exposure-response curve. Under ambient atmospheric conditions iron pentacarbonyl may undergo photochemical decomposition to iron nonacarbonyl and carbon monoxide, or burn to ferric oxide. Read the entire page →
From page 154... ... Under ambient atmospheric conditions iron pentacarbonyl may undergo photochemical decomposition to iron nonacarbonyl and carbon monoxide, or burn to ferric oxide. 154 Prepublication Copy Read the entire page →
From page 155... ... Lethal = All exposed animals died. Prepublication Copy 155 Read the entire page →
From page 156... ... . 156 Prepublication Copy Read the entire page →
From page 157... ... 10 mg/m3 3.4 mg/m3 1.7 mg/m3 0.43 mg/m3 0.21 mg/m3 (Continued on next page) Prepublication Copy 157 Read the entire page →
From page 158... ... Washington, DC: National Academy Press. 158 Prepublication Copy Read the entire page →
From page 159... ... . Prepublication Copy 159 Read the entire page →
From page 160... ... Epidemiologic data do not support the contention that inhalation of nickel carbonyl is carcinogenic to humans. Studies of respiratory tract cancer in nickel workers suggest that nickel dusts, nickel sulfide, and nickel subsulfide may be more relevant than nickel carbonyl, and that nickel carbonyl is not a likely causative agent in the carcinogenicity observed in nickel refinery workers. Read the entire page →
From page 161... ... reported findings of pleural effusion, severe pulmonary congestion, and pulmonary edema for rats that died following exposure to nickel carbonyl. Therefore, the 30-minute exposure to 2.17 ppm was considered a reasonable estimate of an exposure that might cause pulmonary damage in the mouse (most sensitive species tested) Read the entire page →
From page 162... ... The limited acute lethality values for inhalation exposure of humans to nickel carbonyl are summarized in Table 9-3. 162 Prepublication Copy Read the entire page →
From page 163... ... 1970 2.2 Nonlethal Toxicity Shi (1986) reported on 179 cases of nonlethal occupational exposures to nickel carbonyl. Read the entire page →
From page 164... ... Results of experiments in which six human subjects smelled "whiffs" of 0-5 ppm nickel carbonyl (no specific exposure durations were provided) were highly variable with some individuals acknowledging detection of the compound and others being unaware of any odor. Read the entire page →
From page 165... ... and CEC (1990) reported that nickel carbonyl was considered to be an unlikely contributor to the increased risk of sinonasal cancers in the nickel refinery workers. Read the entire page →
From page 166... ... In experiments to study the efficacy of dimercaprol in the treatment of nickel carbonyl poisoning, control rats (those not receiving the dimercaprol) were exposed for 30 minutes to nickel carbonyl at concentrations of 0.20, 0.40, or 0.60 mg/L (equivalent to 28, 56, and, 84 ppm, respectively) Read the entire page →
From page 167... ... as a treatment for nickel carbonyl poisoning, West and Sunderman (1958) exposed four Prepublication Copy 167 Read the entire page →
From page 168... ... Because only one cat died following exposure to <2.00 mg nickel carbonyl/L (280 ppm) , and 3/3 died following exposure to 2.11 168 Prepublication Copy Read the entire page →
From page 169... ... The acute toxicity of nickel carbonyl and the progression of systemic toxicity to lethality limit the identification of critical effects consistent with AEGL-2 endpoints. Prepublication Copy 169 Read the entire page →
From page 170... ... group at 30 minutes and one hour after initiation of the 15-minute exposure. Although these effects per se are indicative of nonlethal responses to nickel carbonyl exposure, the ultimate fate of the nickel carbonylexposed rats was not stated. Read the entire page →
From page 171... ... An exposure response relationship was observed between the incidences of malformations and the nickel carbonyl exposure concentration (Table 9-14) Read the entire page →
From page 172... ... 1979. teratogenic response is likely specific to inhaled nickel carbonyl because such responses were not observed following exposures to divalent nickel salts or following parenterally administered nickel carbonyl. Read the entire page →

From page 123...

... Crotonaldehyde, Trans and Cis +Trans APPENDIX C Category Plot for Crotonaldehyde Chemical Toxicity - TSD All Data Crotonaldehyde 100000.0 Human - No Effect Human - Discomfort 10000.0 Human - Disabling 1000.0 Animal - No Effect ppm 100.0 Animal - Discomfort Animal - Disabling 10.0 AEGL-3 Animal - Some Lethality AEGL-2 1.0 Animal - Lethal AEGL-1 0.1 AEGL 0 60 120 180 240 300 360 420 480 Minutes FIGURE 5-1 Prepublication Copy 123