5

Hydrogen Selenide1

Acute Exposure Guideline Levels

PREFACE

Under the authority of the Federal Advisory Committee Act (FACA) P.L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guideline Levels for Hazardous Substances (NAC/AEGL Committee) has been established to identify, review, and interpret relevant toxicologic and other scientific data and develop AEGLs for high-priority, acutely toxic chemicals.

AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes (min) to 8 hours (h). Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five exposure periods (10 and 30 min and 1, 4, and 8 h) and are distinguished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows:

AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory

_______________________________

1This document was prepared by the AEGL Development Team composed of Carol Wood (Oak Ridge National Laboratory), Heather Carlson-Lynch (SRC, Inc.), and Chemical Managers Nancy Kim (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances) and Ernest V. Falke (U.S. Environmental Protection Agency). The NAC reviewed and revised the document and AEGLs as deemed necessary. Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC committee has concluded that the AEGLs developed in this document are scientifically valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guidelines reports (NRC 1993, 2001).



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement



Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.

OCR for page 236
5 Hydrogen Selenide1 Acute Exposure Guideline Levels PREFACE Under the authority of the Federal Advisory Committee Act (FACA) P.L. 92-463 of 1972, the National Advisory Committee for Acute Exposure Guide- line Levels for Hazardous Substances (NAC/AEGL Committee) has been estab- lished to identify, review, and interpret relevant toxicologic and other scientific data and develop AEGLs for high-priority, acutely toxic chemicals. AEGLs represent threshold exposure limits for the general public and are applicable to emergency exposure periods ranging from 10 minutes (min) to 8 hours (h). Three levels—AEGL-1, AEGL-2, and AEGL-3—are developed for each of five exposure periods (10 and 30 min and 1, 4, and 8 h) and are distin- guished by varying degrees of severity of toxic effects. The three AEGLs are defined as follows: AEGL-1 is the airborne concentration (expressed as parts per million or milligrams per cubic meter [ppm or mg/m3]) of a substance above which it is predicted that the general population, including susceptible individuals, could experience notable discomfort, irritation, or certain asymptomatic, nonsensory 1 This document was prepared by the AEGL Development Team composed of Carol Wood (Oak Ridge National Laboratory), Heather Carlson-Lynch (SRC, Inc.), and Chem- ical Managers Nancy Kim (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances) and Ernest V. Falke (U.S. Environmental Protection Agency). The NAC reviewed and revised the document and AEGLs as deemed necessary. Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels. The NRC committee has concluded that the AEGLs developed in this document are scientifi- cally valid conclusions based on the data reviewed by the NRC and are consistent with the NRC guidelines reports (NRC 1993, 2001). 236

OCR for page 236
Hydrogen Selenide 237 effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure. AEGL-2 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including sus- ceptible individuals, could experience irreversible or other serious, long-lasting adverse health effects or an impaired ability to escape. AEGL-3 is the airborne concentration (expressed as ppm or mg/m3) of a substance above which it is predicted that the general population, including sus- ceptible individuals, could experience life-threatening health effects or death. Airborne concentrations below the AEGL-1 represent exposure concentra- tions that could produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsen- sory effects. With increasing airborne concentrations above each AEGL, there is a progressive increase in the likelihood of occurrence and the severity of effects described for each corresponding AEGL. Although the AEGL values represent threshold concentrations for the general public, including susceptible subpopula- tions, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic respons- es, could experience the effects described at concentrations below the corre- sponding AEGL. SUMMARY Hydrogen selenide is a gas with a disagreeable odor at room temperature. It is formed by the reaction of acids or water with metal selenides (Malczewska- Toth 2012). Although elemental selenium has a wide variety of uses in industry, agriculture, and pharmaceuticals (ATSDR 2003), hydrogen selenide has no commercial use (Malczewska-Toth 2012). Hydrogen selenide is highly irritating to the respiratory tract and effects progress to pulmonary edema, bronchitis, and bronchial pneumonia (Glover 1970; IPCS 1987; Malczewska-Toth 2012). Initial effects in exposed workers are signs of respiratory irritation, include tearing, running nose, coughing, sneez- ing, and chest tightness. The compound is oxidized to elemental selenium when it comes into contact with mucus membranes and appears as a red precipitate (Dudley and Miller 1937, 1941; Glover 1970; Zwart and Arts 1989). A distinct garlic odor of the breath has been reported in people accidentally exposed to selenium or selenium compounds and is most likely the result of the excretion of dimethyl selenide in expired air (ATSDR 2003). No reports of human death after exposure to hydrogen selenide were found in the literature. AIHA (1989) reports an odor threshold of 0.3 ppm for hydrogen selenide. Olfactory fatigue occurs quickly at that concentration, and anecdotal reports indicate that workers exposed to hydrogen selenide at concen- trations greater than 1.5 ppm experienced nasal and throat irritation that was

OCR for page 236
238 Acute Exposure Guideline Levels severe enough that they could not remain at work, but that workers were able to tolerate 0.3 ppm for several minutes without noticeable effects (Dudley and Mil- ler 1941). Dudley and Miller (1937, 1941) performed a series of experiments in which groups of 16-32 guinea pigs (sex and strain not specified) were exposed whole body to various concentrations of hydrogen selenide for 10-480 min and monitored for 30 days. Concentration-related clinical signs of toxicity at concen- trations greater than 6.3 ppm included pawing at the nose and eyes, copious mu- cus from the nasal passages, and difficulty breathing. Marked weight loss was apparent, with recovery in survivors beginning 8 days after exposure. Animals that died within 48 h exhibited respiratory and circulatory failure, whereas those dying after 5 days or later had few acute respiratory symptoms but exhibited bronchial pneumonia for extended periods. The calculated 1-h LC50 (lethal con- centration, 50% lethality) was 3.6 ppm, and 100% lethality occurred at 6.0 ppm. The main finding during histopathologic examination was fatty deposition in the liver and, to a lesser extent, in the kidney; splenic enlargement due to hyperplas- ia of the lymphoid tissue was also found. Hepatic lesions, but no increase in mortality, were observed at concentrations as low as 1.2 ppm for 30-60 min and the lesions generally resolved 17-20 days after exposure. Lethality studies were conducted in pairs of Wistar rats exposed nose-only to various concentrations of hydrogen selenide for different durations, followed by a 14-day observation period (Zwart and Arts 1989; Zwart et al. 1992). In one experiment, no deaths occurred after exposure at 117 ppm for 4 or 15 min, but one animal died after exposure for 7.5 min; thus, 117 ppm for 15 min or less might be a threshold for death. In another experiment, groups of five male and five female Wistar rats were exposed to hydrogen selenide at 47-74 ppm for 1 h. Most deaths occurred within 2 days after exposure. Concentration-related clini- cal signs observed after exposure was stopped included piloerection, red discol- oration of the fur, cyanosis, half-closed eyes, red nasal discharge, mouth breath- ing, moist or dry rales, and apnea. Surviving animals had body weight loss or reduced weight gain throughout the observation period. For example, at 47 ppm, no deaths occurred but four males and two females lost weight throughout the 14-day observation period. Necropsy revealed gas in the stomach or intestines of animals that died during the study and red discolored, atelectatic, edematous, or spongy, swollen, and/or spotted lungs with irregular surface in almost all dece- dents and survivors. A 1-h LC50 of 72 ppm was calculated (Zwart and Arts 1989; Zwart et al. 1992). Examination of the data used to calculate the 1-h LC50 shows a steep dose-response curve (0% mortality at 47 ppm, 20% at 71 ppm, and 60% at 74 ppm). AEGL-1 values are not recommended for hydrogen selenide, because no animal or human data on appropriate end points were found. Data were insuffi- cient to calculate the level of distinct odor awareness for the chemical because the basis of the reported odor threshold of 0.3 ppm was not documented.

OCR for page 236
Hydrogen Selenide 239 Data were also insufficient to calculate AEGL-2 values for hydrogen sele- nide. In the absence of specific data for determining an AEGL-2 value, one-third of the AEGL-3 values can be used to establish AEGL-2 values (NRC 2001). This approach is justified because the lethality data in rats indicate a steep con- centration-response relationship. AEGL-3 values for hydrogen selenide were based on an estimated LC01 of 33 ppm, obtained by a log-probit analysis of data from experiments in Wistar rats (Zwart and Arts 1989; Zwart et al. 1992). Values were scaled using the equation Cn × t = k, where n ranges from 0.8 to 3.5 (ten Berge et al. 1986). A value of n = 2.5 was calculated by probit analysis of all of the available lethality data in the rat. A total uncertainty factor of 100 was applied (10 for interspecies differences and 10 for intraspecies variability). The intraspecies factor of 10 was selected to address uncertainty about the mechanism of action for the marked body-weight loss exhibited by some surviving rats and whether this reflected a moribund state. An interspecies factor of 10 was used, because data were availa- ble in only two species and the limited data suggest that the rat might not be the most sensitive species. AEGL values for hydrogen selenide are presented in Table 5-1. 1. INTRODUCTION Hydrogen selenide is a gas with a disagreeable odor at room temperature. It has a density greater than that of air and is formed by the reaction of acids or water with metal selenides (Malczewska-Toth 2012). Although elemental sele- nium has a wide variety of uses in industry, agriculture, and pharmaceuticals (ATSDR 2003), hydrogen selenide has no commercial use (Malczewska-Toth 2012). Hydrogen selenide is highly irritating to the respiratory tract with effects progressing to pulmonary edema, bronchitis, and bronchial pneumonia (Glover 1970; Malczewska-Toth 2012). The compound is oxidized to elemental seleni- um when it comes into contact with mucus membranes, and appears as a red precipitate (Dudley and Miller 1937, 1941; Glover 1970; Zwart and Arts 1989). The breath of people accidentally exposed to selenium or selenium compounds has been reported to have a distinct garlic odor, most likely the result of excre- tion of dimethyl selenide in expired air (ATSDR 2003). The chemical and physical properties of hydrogen selenide are listed in Table 5-2. 2. HUMAN TOXICITY DATA 2.1. Acute Lethality No reports of human lethality following exposure to hydrogen selenide were found in the available literature.

OCR for page 236
240 Acute Exposure Guideline Levels TABLE 5-1 AEGL Values for Hydrogen Selenide End Point Classification 10 min 30 min 1h 4h 8h (Reference) AEGL-1 NRa NRa NRa NRa NRa Insufficient data (nondisabling) AEGL-2 0.22 ppm 0.15 ppm 0.11 ppm 0.064 ppm 0.048 ppm One-third of the (disabling) (0.73 (0.48 (0.37 (21 (0.16 AEGL-3 values mg/m3) mg/m3) mg/m3) mg/m3) mg/m3) AEGL-3 0.67 ppm 0.44 ppm 0.33 ppm 0.19 ppm 0.14 ppm Calculated 1-h (lethal) (2.2 (1.5 (1.1 (0.63 (0.48 LC01 in rats (Zwart mg/m3) mg/m3) mg/m3) mg/m3) mg/m3) and Arts 1989; Zwart et al. 1992) a Not recommended. Absence of an AEGL-1 value does not imply that exposure below the AEGL-2 value is without adverse effects. Abbreviations: LC01, lethal concentration, 1% lethality; NR, not recommended. TABLE 5-2 Chemical and Physical Properties of Hydrogen Selenide Parameter Value Reference Synonyms Dihydrogen selenide, selenium hydride, ATSDR 2003 selenium dihydride, selane CAS registry no. 7783-07-5 O’Neil et al. 2006 Chemical formula H2Se Molecular weight 80.98 O’Neil et al. 2006 Physical state Colorless gas ATSDR 2003 Melting point -65.73°C O’Neil et al. 2006 Boiling point -41.3°C O’Neil et al. 2006 Liquid density (water = 1) 2.12 at -42°C/4°C O’Neil et al. 2006 Solubility in water 377 mL/100 mL at 4°C O’Neil et al. 2006 Vapor density (air = 1) 2.80 Yaws 2001 Vapor pressure 9,120 mm Hg (12 atm) at 30.8°C ATSDR 2003; O’Neil et al. 2006 Conversion factors 1 ppm = 3.3 mg/m3 NIOSH 2011 1 mg/m3 = 0.3 ppm 2.2. Nonlethal Toxicity Odor thresholds for hydrogen selenide are reported to range from 0.0005 to 3.6 ppm, with irritation reported at 1.8 ppm; the odor was described as de- cayed horseradish (Ruth 1986). AIHA (1989) lists the odor threshold as 0.3 ppm. Olfactory fatigue occurs quickly at this concentration (Dudley and Miller 1941).

OCR for page 236
Hydrogen Selenide 241 2.2.1. Case Reports Dudley and Miller (1941) reported that workers exposed to concentrations of hydrogen selenide greater than 1.5 ppm experienced nasal and throat irritation that was so severe that they could not remain at work. Workers were able to tolerate 0.3 ppm for several minutes without noticeable effects. However, these observations were reported in the discussion section of the paper without a cita- tion or information on any associated sampling or analysis. Twenty-five workers engaged in various metal etching, buffering, and pol- ishing operations were exposed to hydrogen selenide in a large workroom (Buchan 1947). A reaction of selenious acid in the ink with metal was identified as the source of the hydrogen selenide. The breath of all of the exposed workers had a distinct garlic odor, but five had recently eaten food containing garlic. Only five complained of symptoms, including nausea, vomiting, metallic taste in the mouth, dizziness, extreme lassitude, and fatigue. No correlation was found between symptoms and urinary concentrations of selenium. Air samples were taken at six sites in the room; although a visible precipitate was observed on the filter paper, the measured concentration of hydrogen selenide did not exceed the detection limit of 0.2 ppm for the titrometric method. Additional details of the analytic methods were not described. However, the possibility that the highest concentrations were reached close to the breathing zone of the workers was not- ed by the authors. A review chapter describing this study (Glover et al. 1979) reported that “Five cases of subacute industrial selenosis were reported as due to exposure to less than 0.07 mg/m3 of H2Se”; however, that concentration appears to be an erroneous conversion from the detection limit of 0.2 ppm (the correct conversion would be 0.7 mg/m3). Other early reports of symptoms in workers exposed to hydrogen selenide have been summarized by Glover (1970) and IPCS (1987). Initial effects are of respiratory irritation and include tearing, running nose, coughing, sneezing, and tightness of the chest. A latent period of several hours may follow, after which pulmonary edema occurs. Affected workers all had complete recovery, but no exposure concentrations were measured. A chemist exposed to a “high concen- tration” of hydrogen selenide developed hyperglycemia that was controllable by increasing doses of insulin (Rosenfeld and Beath 1964; Malczewska-Toth 2012). Banerjee et al. (1997) described effects in 31 workers exposed to “toxic fumes” produced during refining or recovery of scrap metal. The initial clinical presentation included intense cough, suffocation, burning, severe water dis- charge from eyes, cyanosis, tachypnea, tachycardia, and severe bronchospasm. Most workers recovered within 7 days; however, four with respiratory diseases associated with heavy smoking (one with acute respiratory distress syndrome, one with bilateral emphysema, two with chronic obstructive pulmonary disease) were treated for more than 3 weeks. Blood selenium concentrations did not cor- relate with symptoms; only four samples had selenium concentrations in the range of 71-189 μg/L on the first day. Selenium was confirmed in soil and wall- scratch samples from the incident site but no exposures could be determined.

OCR for page 236
242 Acute Exposure Guideline Levels Workers were exposed to selenium fume while smelting scrap aluminum contaminated with metallic selenium (Clinton 1947). A reddish cloud was re- leased into the plant when the contents of a furnace were stirred in preparation for pouring; no concentrations were measured and the author estimated that no worker was exposed for more than 2 min. All exposed workers had intense irri- tation of the eyes, nose, and throat and headache developed several hours later. In addition, one worker with potentially higher exposure developed severe dyspnea 8-12 h after the accident. All workers appeared completely well in 3 days. A 24-year old male was accidentally exposed to hydrogen selenide while transferring the gas from one cylinder to another (Schecter et al. 1980). Immedi- ate symptoms included burning of the eyes and throat and was followed by coughing and wheezing. He was hospitalized 18 h later due to recurrent cough and dyspnea. Chest X-ray revealed pneumomediastinum and subcutaneous em- physema. Results of most pulmonary function tests returned to predicted levels within 30 days of the accident. However, abnormalities in flows at 50% and 25% of vital capacity persisted for up to 3 years. A female college student was exposed to hydrogen selenide gas at least once a week for one year while working in a research laboratory (Alderman and Bergin 1986). She complained of chronic diarrhea and abdominal pain, had con- junctivitis and nasal stuffiness, and six dental caries had recently developed. She also had granular conjunctivitis, breath with a distinct garlic-like odor, and prominent transverse ridges of the fingernails. Chronic selenosis was diagnosed, which resolved after exposure ended. No exposure measurements were made in the research laboratory. Another report described exposure of a researcher once a week for 2 years to selenium vapors produced by evaporation of pure selenium in an evacuated container (Ducloux et al. 1976). Symptoms included eczema of the face, weak- ness, and bronchitis. No other details were given. 2.2.2. Epidemiologic Studies No epidemiologic studies of exposure to hydrogen selenide were found. 2.3. Neurotoxicity No information regarding the neurotoxicity of hydrogen selenide in hu- mans was found. 2.4. Developmental and Reproductive Toxicity No information regarding the developmental or reproductive toxicity of hydrogen selenide in humans was found.

OCR for page 236
Hydrogen Selenide 243 2.5. Genotoxicity No information regarding the genotoxicity of hydrogen selenide in hu- mans was found. 2.6. Carcinogenicity No information regarding the carcinogenicity of hydrogen selenide in hu- mans was found. A study of smelter workers found that those who died of lung cancer had lower selenium concentrations than either controls or workers who died of other causes (Gerhardsson et al. 1986). EPA (1993) has judged that sele- nium and selenium compounds are not classifiable as to their carcinogenicity in humans because of inadequate human data and inadequate evidence of carcino- genicity in animals. However, the agency found the evidence on selenium sul- fide to be sufficient for classifying it as a probable human carcinogen classifica- tion. 2.7. Summary Hydrogen selenide is highly irritating to the respiratory tract with effects progressing to pulmonary edema, bronchitis, and bronchial pneumonia (Glover 1970; Malczewska-Toth 2012). Irritation occurs at or below the odor threshold (Ruth 1986). 3. ANIMAL TOXICITY DATA 3.1. Acute Lethality 3.1.1. Guinea Pigs Dudley and Miller (1937, 1941) performed a series of experiments in which groups of 16 or 32 guinea pigs (sex and strain not specified) were ex- posed whole body to various concentrations of hydrogen selenide (0.001- 0.57 mg/L or 0.3-171 ppm) for 10, 30, 60, 120, 240, or 480 min and were monitored for 30 days. Chamber atmospheres were calibrated prior to exposures and ana- lytic concentrations were measured by weighing precipitated selenium from air samples. Clinical signs of toxicity from exposure at concentrations of 0.021 mg/L (6.3 ppm) or higher included pawing at the nose and eyes, copious mucus from the nasal passages, and difficulty breathing. At concentrations less than 0.021 mg/L (6.3 ppm) for up to 8 h, nasal discharge was less marked and severe ocular and nasal irritation were not observed; difficulty breathing was not ob- served until 24 h after exposure. Decomposition of the chemical by the mucus in the nasal passages resulted in a deposit of red, amorphous selenium on the nose and head of the animals. Marked weight loss was apparent with recovery in sur-

OCR for page 236
244 Acute Exposure Guideline Levels vivors beginning 8 days after exposure. Animals that died within 48 h exhibited respiratory and circulatory failure whereas those that died after 5 days or later had few acute respiratory symptoms but exhibited bronchial pneumonia for ex- tended periods. More importantly, even for concentrations greater than the LC50, the majority of deaths occurred more than 5 days after exposure; the peak oc- curred at 8-10 days, which likely corresponded to evidence of hepatic damage (see discussion of histopathologic findings below). The investigators did not report LC50 values; however, on the basis of the lethality data from the study, LC50 values were calculated to be 0.34, 0.020, 0.012, 0.012, 0.012, and 0.0054 mg/ L (102, 6.0, 3.6, 3.6, 3.6, and 1.6 ppm) for 10, 30, 60, 120, 240, and 480 min, respectively. A few animals (1-3) died in each of the control groups, so the reliability of these data and the calculated LC50 values is uncertain. Regardless, a marked increase in deaths (resulting in more than 35% lethality) was consistently seen at 3.3-3.6 ppm for durations of 30-240 min. Histopathologic examinations were performed on the animals used in the lethality studies (Dudley and Miller 1937, 1941), but severity scores were not determined. The main finding was fatty deposition in the liver and, to a lesser extent, in the kidney. Splenic enlargement due to hyperplasia of the lymphoid tissue was also found. Hepatic lesions, but no increase in mortality, were ob- served at concentrations as low as 1.3 ppm for 30-60 min. Fatty changes became progressively more severe for up to 10 days and generally resolved by 17-20 days after exposure. Slight to moderate thickening of the alveolar wall was found in the lung of almost all animals and acute pneumonia that progressed to bronchopneumonia occurred in about half of the animals. Most importantly, the severity of the pathologic lesions was more closely related to the amount of time between exposure and death than to the concentration or duration of exposure. 3.1.2. Rats Two lethality studies were conducted in Wistar rats exposed nose-only to various concentrations of hydrogen selenide for different durations followed by a 14-day observation period (Zwart and Arts 1989; Zwart et al. 1992). The mor- tality results are summarized in Table 5-3. Test atmospheres were measured by atomic absorption spectrometry. In the first experiment (Study A or C × t study), groups of one male and one female rat were exposed at concentrations of 0.13- 2.9 g/m3 (39-870 ppm) for durations of 4-120 min. At 0.39 g/m3 (117 ppm), no deaths occurred following exposures for 4 and 15 min, but one animal died dur- ing the observation period following exposure for 7.5 min; thus, 117 ppm for 15 min or less may be a threshold for death. Nearly all animals exposed to hydro- gen selenide at 78 ppm or greater for 30 min or more died. At a concentration of 39 ppm, no animals died following exposure for up to 60 min, but one of two died following exposure for 84 or 120 min. Most deaths occurred within 2 days

OCR for page 236
Hydrogen Selenide 245 after exposure. Concentration-related clinical signs included piloerection, red discoloration of the fur, cyanosis, half-closed eyes, red nasal discharge, mouth breathing, moist or dry rales, and apnea. For animals exposed at 39 ppm, “breathing problems” recurred during week 2 of the observation period. Surviv- ing animals had body weight loss or reduced weight gain throughout the obser- vation period. Necropsy revealed gas in the stomach or intestines of animals that died during the study and red discolored, atelectatic, edematous, or spongy, swollen, and/or spotted lungs with irregular surface in almost all decedents and survivors. The authors reported a 1-h LC50 of 0.18 g/m3 (54 ppm). In the second experiment (Study B or 1-h LC50 study), groups of five male and five female Wistar rats were exposed nose-only to hydrogen selenide at 0.155, 0.235, or 0.245 g/m3 (47, 71, or 74 ppm) for 1 h. Clinical signs, effects on body weight, and gross findings were similar to those described above for the first experiment. At 0.155 g/m3 (47 ppm), four males and two females had body weight loss throughout the 14-day observation period. A 1-h LC50 of 0.24 g/m3 (72 ppm) was calculated (Zwart and Arts 1989; Zwart et al. 1992). Examination of the data used to calculate the 1-h LC50 shows a steep concentration-response curve (see Table 5-3). On the basis of marked body weight loss among survivors (which suggest- ed the animals were moribund) during the observation periods of both experi- ments, the investigators postulated that the LC50 estimates would have been lower if the observation periods had been longer. However, extending the obser- vation period was not considered ethical due to the condition of the animals. Zwart and Arts (1989) suggested that animals that lost weight during days 8-14 of the observation period could be considered “dead”, and estimated that this approach would yield a 1-h LC50 of 0.06-0.07 g/m3 (18-21 ppm). TABLE 5-3 Lethality in Rats Exposed to Hydrogen Selenide Concentration 4-20 min 30 min 60 min 120 min Study A (C × t study) 0.13 g/m3 (39 ppm) NR 0/2 0/2 1/2 3 0.26 g/m (78 ppm) NR 2/2 2/2 2/2 3 0.39 g/m (117 ppm) 1/6 2/2 2/2 NR 1.41 g/m3 (423 ppm) 10/10 NR NR NR 3 2.90 g/m (870 ppm) 8/8 2/2 NR NR Study B (1-h LC50 study) 155 g/m3 (47 ppm) NR NR 0/10 NR 3 235 g/m (71 ppm) NR NR 2/10 NR 245 g/m3 (74 ppm) NR NR 6/10 NR Abbreviations: LC50, lethal concentration, 50% lethality; NR, not reported. Source: Zwart and Arts 1989; Zwart et al. 1992.

OCR for page 236
246 Acute Exposure Guideline Levels 3.2. Nonlethal Toxicity Groups of five young, female albino rats were exposed to selenium fumes produced by passing a current through tungsten wire wound in a cone and filled with chips of selenium (Hall et al. 1951). The exposure concentration, particle size, and chemical form were not specified. Exposures were for 2-16 min and animals were killed 1-16 days following exposure. At necropsy, lung weights were increased and hemorrhage with scattered emphysematous and atelectatic areas were observed. Little evidence of repair was apparent up to 16 days after exposure. 3.3. Neurotoxicity No evidence of a narcotic or anesthetic effect was seen in guinea pigs ex- posed to lethal concentrations of hydrogen selenide for up to 8 h (Dudley and Miller 1937, 1941). 3.4. Developmental and Reproductive Toxicity No information on the developmental or reproductive toxicity of hydrogen selenide in animals was found. Selenium or selenium compounds have produced defects in the chick when applied to the air cell, and decreased live births and pup size in mice when administered orally or by injection; no adverse effects have been found in hamsters or monkeys (Shepard 2010). 3.5. Genotoxicity No information on the genotoxicity of hydrogen selenide was found. So- dium selenite and sodium selenide, which are metabolized to hydrogen selenide, induced DNA single-strand breaks and growth inhibition in a mouse mammary carcinoma cell line (Lu et al. 1995). Hydrogen selenide was not measured in the culture medium. 3.6. Chronic Toxicity and Carcinogenicity No information on the chronic toxicity or carcinogenicity of hydrogen selenide in laboratory animals was found. In studies of selenium sulfide and Selsun (2.5% selenium sulfide), no evidence of carcinogenicity was found fol- lowing dermal application of either compound to the skin of male and female ICR mice three times per week for 86-88 weeks (NTP 1980 a,b). However, these studies were considered inadequate because of their short duration due to the limited lifetime of the test stain of mice.

OCR for page 236
256 Acute Exposure Guideline Levels OSHA standard for hydrogen selenide was derived in 1978, but the supporting documentation (29 CFR 1910.1000 [2006]) does not describe how the value was derived. In addition to the guidelines presented in Table 5-7, the state of California has adopted 0.002 ppm (0.005 mg/m3) as the acute reference exposure level for hydrogen selenide (CalEPA 2007). This concentration is based on data from studies in guinea pigs by Dudley and Miller (1937, 1941). 8.3. Data Adequacy and Research Needs Little human or animal data on hydrogen selenide are available. Although symptoms in humans were well described, case reports did not include reliable exposure concentrations. Two well-conducted animal lethality studies were available, but the study in guinea pigs suffered from a variety of limitations, including potential exposure via multiple routes, use of a more uncertain analyt- ic technique to estimate exposure concentrations, and unexplained control mor- talities (see Section 4.4.1). Thus, it is difficult to draw conclusions regarding species differences (if any). 9. REFERENCES ACGIH (American Conference of Government and Industrial Hygienists). 2001. Hydro- gen selenide (CAS Reg. No. 7783-07-5). Documentation of the Threshold Limit Values and Biological Exposure Indices, 7th Ed. American Conference of Gov- ernment and Industrial Hygienists, Cincinnati, OH. ACGIH (American Conference of Government and Industrial Hygienists). 2012. Hydro- gen selenide (CAS Reg. No. 7783-07-5). P. 35 in TLVs and BEIs Based on the Documentation of the Threshold Limit Values for Chemical Substances and Physi- cal Agents & Biological Exposure Indices. American Conference of Government and Industrial Hygienists, Cincinnati, OH. AIHA (American Industrial Hygiene Association). 1989. P. 20 in Odor Thresholds for Chemicals with Established Occupational Health Standards. Fairfax, VA: Ameri- can Industrial Hygiene Association. AIHA (American Industrial Hygiene Association). 2002. Emergency Response Planning Guidelines: Hydrogen selenide. Fairfax, VA: American Industrial Hygiene Associa- tion. AIHA (American Industrial Hygiene Association). 2013. P. 26 in ERPG/WEEL Hand- book. American Industrial Hygiene Association [online]. Available: https://www. aiha.org/get-involved/AIHAGuidelineFoundation/EmergencyResponsePlanningGu idelines/Documents/2013ERPGValues.pdf [accessed Jan. 3, 2014]. Alderman, L.C., and J.J. Bergin. 1986. Hydrogen selenide poisoning: An illustrative case with review of the literature. Arch. Environ. Health 41(6):354-358. ATSDR (Agency for Toxic Substances and Disease Registry). 2003. Toxicological Pro- file for Selenium. U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA. Sep- tember 2003 [online]. Available: http://www.atsdr.cdc.gov/toxprofiles/tp92.pdf [accessed Jan. 3, 2014].

OCR for page 236
Hydrogen Selenide 257 Banerjee, B.D., S. Dwivedi, and S. Singh. 1997. Acute hydrogen selenide gas poisoning admissions in one of the hospitals in Delhi, India: Case report. Hum. Exp. Toxicol. 16(5):276-278. Buchan, R.F. 1947. Industrial selenosis; A review of the literature, report of five cases and a general bibliography. Occup. Med. 3(5):439-456. CalEPA (California Environmental Protection Agency). 2007. Acute Reference Exposure Level (RELs). Air Toxicology and Epidemiology, Office of Environmental Health Hazard Assessment, California Environmental Protection Agency [online]. Avail- able: http://oehha.ca.gov/air/allrels.html [accessed Jan. 3, 2014] Clinton, M. 1947. Selenium fume exposure. J. Ind. Hyg. Toxicol. 29(4):225. DFG (Deutsche Forschungsgemeinschaft). 2012. Substance Overview for Hydrogen Selenide. The MAK Collection for Occupational Health and Safety. Wiley [online]. Available: http://onlinelibrary.wiley.com/doi/10.1002/3527600418.mbe7 78307/full [accessed Jan. 3, 2014]. Ducloux, J.P., B. Ducloux, P. Frantz, and V. Vincent. 1976. Recording a selenium intoxi- cation. Review of the literature. Acta Pharmacol. Toxicol. 41(suppl. 2):427. Dudley, H.C., and J.W. Miller. 1937. Toxicology of selenium. IV. Effects of exposure to hydrogen selenide. Public Health Rep. 52(36):1217-1231. Dudley, H.C., and J.W. Miller. 1941. Toxicology of selenium. VI. Effects of subacute exposure to hydrogen selenide. J. Ind. Hyg. Toxicol. 23(10):470-477. EPA (U.S. Environmental Protection Agency). 1993. Selenium and Compounds (CAS Reg. No. 7782-49-2). Carcinogenicity Assessment, Integrated Risk Information System, U.S. Environmental Protection Agency [online]. Available: http://www. epa.gov/iris/subst/0472.htLC [accessed Aug. 17, 2012]. Gasiewicz, T.A., and J.C. Smith. 1978. The metabolism of selenite by intact rat erythro- cytes in vitro. Chem. Biol. Interact. 21(2-3):299-313. Gerhardsson, L., D. Brune, G.F. Nordberg, and P.O. Wester. 1986. Selenium and other trace elements in lung tissue in smelter workers relationship to the occurrence of lung cancer. Acta Pharmacol. Toxicol. 59(suppl. 7):256-259. Glover, J.R. 1970. Selenium and its industrial toxicology. IMS Ind. Med. Surg. 39(1):50- 54. Glover J., O. Levander, J. Parizek, and V. Vouk. 1979. Selenium. Pp. 555-557 in Hand- book on the Toxicology of Metals, L. Friberg, G.F. Norberg, and V. Vouk, eds. Amsterdam: Elsevier/North Holland Biomedical Press. Hall, R.H., S. Laskin, P. Frank, E.A. Maynard, and H.C. Hodge. 1951. Preliminary observa- tions on toxicity of elemental selenium. AMA Arch. Ind. Hyg. Occup. Med. 4(5):458-464. IPCS (International Programme on Chemical Safety). 1987. Selenium. Environmental Health Criteria 58. World Health Organization, Geneva, Switzerland [online]. Avail- able: http://www.inchem.org/documents/ehc/ehc/ehc58.htm [accessed Jan. 2, 2014]. Lee, M., A. Dong, and J. Yano. 1969. Metabolism of 75Se-selenite by human whole blood in vitro. Can. J. Biochem. 47(8):791-797. Lu, J., C. Jiang, M. Kaeck, H. Ganther, S. Vadhanavikit, C. Ip, and H. Thompson. 1995. Dissociation of the genotoxic and growth inhibitory effects of selenium. Biochem. Pharmacol. 50(2):213-219. Malczewska-Toth, B. 2012. Phosphorus, selenium, tellurium, and sulfur. Pp. 841-884 in Patty's Industrial Hygiene and Toxicology. New York: Wiley. Medinsky, M.A., R.G. Cuddihy, W.C. Griffith, and R.O. McClellan. 1981. A simulation model describing the metabolism of inhaled and ingested selenium compounds. Toxicol. Appl. Pharmacol. 59(1):54-63.

OCR for page 236
258 Acute Exposure Guideline Levels MSZW (Ministerie van Sociale Zaken en Werkgelegenheid). 2004. Nationale MAC-lijst 2004: Seleen en verbindingen. Den Haag: SDU Uitgevers [online]. Available: http://www.lasrook.net/lasrookNL/maclijst2004.htm [accessed Jan. 3, 2014]. NIOSH (National Institute for Occupational Safety and Health). 1994. Documentation for Immediately Dangerous to Life or Health Concentrations (IDLHs): Hydrogen Selenide (as Se). U.S. Department of Health and Human Services, Centers for Dis- ease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, OH [online]. Available: http://www.cdc.gov/niosh/idlh/77830 75.html [accessed Aug. 17, 2012]. NIOSH (National Institute for Occupational Safety and Health). 2011. NIOSH Pocket Guide to Chemical Hazards: Hydrogen Selenide. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, OH [online]. Available: http:// www.cdc.gov/niosh/npg/npgd0336.html [accessed Aug. 17, 2012]. NRC (National Research Council). 1993. Guidelines for Developing Community Emer- gency Exposure Levels for Hazardous Substances. Washington, DC: National Academy Press. NRC (National Research Council). 2001. P. 43 in Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals. Washing- ton, DC: National Academy Press. NTP (National Toxicology Program). 1980a. Bioassay of Selenium Sulfide (Dermal Study) for Possible Carcinogenicity. Technical Report No. 197. NTP No. 80-18. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, Bethesda, MD, and National Toxi- cology Program, Research Triangle Park, NC [online]. Available: http://ntp.niehs. nih.gov/ntp/htdocs/LT_rpts/TR197.pdf [accessed Jan. 2, 2014]. NTP (National Toxicology Program). 1980b. Bioassay of Selsun for Possible Carcino- genicity. Technical Report No. 199. NTP No. 80-19. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute, Bethesda, MD, and National Toxicology Program, Research Tri- angle Park, NC [online]. Available: http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr1 99.pdf [accessed Jan. 2, 2014]. O’Neil, M.J., P.E. Heckelman, C.B. Koch, and K.J. Roman, eds. 2006. Hydrogen sele- nide. P. 831inThe Merck Index: An Encyclopedia of Chemicals, Drugs, and Bio- logicals, 14th Ed. Whitehouse Station, NJ: Merck. Rosenfeld, I., and O.A. Beath. 1964. Selenium: Geobotany, Biochemistry, Toxicity, and Nutrition. New York: Academic Press. 411 pp. RTECS (Registry of Toxic Effects of of Chemical Substances). 2009. Hydrogen selenide. RTECS No. MX1050000 [online]. Available: http://www.cdc.gov/niosh-rtecs/MX 100590.html [accessed Jan. 3, 2014]. Ruth, J.H. 1986. Odor thresholds and irritation levels of several chemical substances: A review. Am. Ind. Hyg. Assoc. J. 47(3):A142-A151. Schecter, A., W. Shanske, A. Stenzler, H. Quintilian, and H. Steinberg. 1980. Acute hy- drogen selenide inhalation. Chest 77(4):554-555. Shepard, T.H. 2010. P. 383 in Catalog of Teratogenic Agents, 13th Ed. Baltimore, MD: The Johns Hopkins University Press. Sunde, R.A. 1990. Molecular biology of selenoproteins. Annu. Rev. Nutr. 10:451-474. ten Berge, W.F., A. Zwart, and L.M. Appelman. 1986. Concentration-time mortality response relationship of irritant and systemically acting vapours and gases. J. Haz- ard. Mater. 13(3):301-309.

OCR for page 236
Hydrogen Selenide 259 Weissman, S.H., R.G. Cuddihy, and M.A. Medinsky. 1983. Absorption, distribution, and retention of inhaled selenious acid and selenium metal aerosols in beagle dogs. Toxicol. Appl. Pharmacol. 67(3):331-337. Yaws, C.L., ed. 2001. Pp. 404-407 in Matheson Gas Data Book, 7th Ed. New York: McGraw-Hill. Zwart, A., and J.H.E. Arts. 1989. Acute (1-hour) Inhalation Toxicity Study with Hydrogen Selenide in Rats. Report No. V 89.463. Zeist, The Netherlands: TNO-CIVO Insti- tutes. Zwart, A., J.H. Arts, W.J. ten Berge, and L.M. Appleman. 1992. Alternative acute inhala- tion toxicity testing by determination of the concentration-time-mortality relation- ship: Experimental comparison with standard LC50 testing. Regul. Toxicol. Phar- macol. 15(3):278-290.

OCR for page 236
260 Acute Exposure Guideline Levels APPENDIX A DERIVATION OF AEGL VALUES Derivation of AEGL-1 Values AEGL-1 values for hydrogen selenide are not recommended. No animal or human data on appropriate end points were found. A level of distinct odor awareness could not be calculated because the reported odor threshold of 0.3 ppm was not doc- umented. In addition, AEGL-1 values based on irritation may not account for de- layed onset of pulmonary edema. Derivation of AEGL-2 Values In the absence of relevant data to derive AEGL-2 values and because hydro- gen selenide has a steep concentration-response relationship, AEGL-3 values were divided by 3 to estimate AEGL-2 values (NRC 2001). Calculations: 10-min AEGL-2: 0.67 ppm ÷ 3 = 0.22 ppm 30-min AEGL-2: 0.44 ppm ÷ 3 = 0.15 ppm 1-h AEGL-2: 0.33 ppm ÷ 3 = 0.11 ppm 4-h AEGL-2: 0.19 ppm ÷ 3 = 0.064 ppm 8-h AEGL-2: 0.14 ppm ÷ 3 = 0.048 ppm Derivation of AEGL-3 Key studies: Zwart, A., and J.H.E. Arts. 1989. Acute (1-hour) Inhalation Toxicity Study with Hydrogen Selenide in rats. Report No. V 89.463. Zeist, The Netherlands: TNO-CIVO Institutes. Zwart, A., J.H.E. Arts, W.J. ten Berge, and L.M. Appleman. 1992. Alternative acute inhalation toxicity testing by determination of the concentration-time- mortality relationship: Experimental comparison with standard LC50 testing. Regul. Toxicol. Pharmacol. 15(3):278-290. Toxicity end point: 1-h LC01 of 33 ppm, calculated by log-probit analysis of the combined lethality data from the two experiments in rats (1-h LC50 study and C × t study).

OCR for page 236
Hydrogen Selenide 261 Time scaling: Cn × t = k (n = 2.5, based on probit analysis of the combined lethality data) Uncertainty factors: 10 for interspecies differences 10 for intraspecies variability Modifying factor: None Calculations: 10-min AEGL-3: C2.5 × 0.167 h = 6,255.829 ppm-h C = (6,255.829 ppm-h ÷ 0.167 h)1/2.5 = 67.04 ppm 67.04 ÷ 100 = 0.67 30-min AEGL-3: C2.5 × 0.5 h = 6,255.829 ppm-h C = (6,255.829 ppm-h ÷ 0.5 h)1/2.5 = 43.54 ppm 43.54 ÷ 100 = 0.44 1-h AEGL-3: C = 33 ppm 33 ÷ 100 = 0.33 ppm 4-h AEGL-3: C2.5 × 4 h = 6,255.829 ppm-h C = (6,255.829 ppm-h ÷ 4 h)1/2.5 = 18.95 18.95 ÷ 100 = 0.19 ppm 8-h AEGL-3: C2.5 × 8 h = 6,255.829 ppm-h C = (6,255.829 ppm-h ÷ 8 h)1/2.5 = 14.36 ppm 14.36 ÷ 100 = 0.14

OCR for page 236
262 Acute Exposure Guideline Levels APPENDIX B DERIVATION SUMMARY FOR HYDROGEN SELENIDE AEGL-1 VALUES AEGL-1 values for hydrogen selenide are not recommended because of insuf- ficient data. No animal or human data on appropriate end points were found. A level of distinct odor awareness could not be calculated because the reported odor thresh- old of 0.3 ppm was not documented. In addition, AEGL-1 values may not account for pulmonary edema, which may occur from exposures resulting in irritation after a latency period. AEGL-2 VALUES 10 min 30 min 1h 4h 8h 0.22 ppm 0.15 ppm 0.11ppm 0.064 ppm 0.048 ppm Data adequacy: No data with appropriate end points for deriving AEGL-2 values were available. Therefore, one-third of the AEGL-3 values were used to estimate AEGL-2 values (NRC 2001). AEGL-3 VALUES 10 min 30 min 1h 4h 8h 0.67 ppm 0.44 ppm 0.33 ppm 0.19 ppm 0.14 ppm Key references: Zwart, A., and J.H.E. Arts. 1989. Acute (1-h) Inhalation Toxicity Study with Hydrogen Selenide in Rats. Report No. V 89.463. Zeist, The Netherlands: TNO-CIVO Institutes. Zwart, A., J.H.E. Arts, W.J. ten Berge, and L.M. Appleman. 1992. Alternative acute inhalation toxicity testing by determination of the concentration-time-mortality relationship: Experimental comparison with standard LC50 testing. Regul. Toxicol. Pharmacol. 15(3):278-290. Test species/Strain/Number: Rat (males and females), Wistar, 2-10 per group Exposure route/Concentrations/Durations: Nose-only; 39-870 ppm; 4-120 min Effects: Mortality (incidence); clinical signs of irritation occurred at all concentrations ≥ 423 ppm for ≥4 min: 2/2 117 ppm for 4 min: 0/2 117 ppm for 7.5 min: 1/2 117 ppm for 15 min: 0/2 117 ppm for 30 min: 2/2 78 ppm for 30 min: 2/2 39 ppm for 30 min: 0/2 39 ppm for 42 min: 0/2 117 ppm for 60 min: 2/2 78 ppm for 60 min: 2/2 74 ppm for 60 min: 6/10

OCR for page 236
Hydrogen Selenide 263 71 ppm for 60 min: 2/10 47 ppm for 60 min: 0/10 39 ppm for 60 min: 0/2 78 ppm for 60 min: 2/2 78 ppm for 84 min: 2/2 39 ppm for 84 min: 1/2 39 ppm for 120 min: 1/2 78 ppm for 120 min: 2/2 End point/Concentration/Rationale: LC01 of 33 ppm, calculated by log-probit analysis of combined data from the two studies Uncertainty factors/Rationale: Total uncertainty factor: 100 Interspecies: 10; data are available in only two species, and the rat is not the most sensitive species Intraspecies: 10; although the steepness of concentration-response relationship indicates little individual variation, this factor was applied to account for the uncertainty with respect to the mechanism for and long-term implications of marked body weight loss in surviving rats Modifying factor: None Animal-to-human dosimetric adjustment: Not applicable Time scaling: Cn × t = k where n = 2.5. Empirical value of n calculated from log probit analysis of rat lethality data combined from the two studies. Data adequacy: Limited data are available for hydrogen selenide. AEGL-3 values were based on a well-conducted and documented study. Exposures were by nose-only administration, which eliminated potential confounding exposure routes.

OCR for page 236
264 Acute Exposure Guideline Levels APPENDIX C CATEGORY PLOT FOR HYDROGEN SELENIDE FIGURE C-1 Category plot of toxicity data and AEGL values for hydrogen selenide. Note: There are no documented human data on hydrogen selenide; anectodal information reported by Dudley and Miller (1941) is considered unreliable because no citation was provided nor did the authors indicate sampling or analysis methods to supporting their statements. Guinea pig data are not included because a large number of deaths occurred in the control groups for this study.

OCR for page 236
TABLE C-1 Data Used in Category Plot for Hydrogen Selenide Source Species Sex No. exposures ppm Minutes Category Effect AEGL-1 NR 10 AEGL AEGL-1 NR 30 AEGL AEGL-1 NR 60 AEGL AEGL-1 NR 240 AEGL AEGL-1 NR 480 AEGL AEGL-2 0.22 10 AEGL AEGL-2 0.14 30 AEGL AEGL-2 0.11 60 AEGL AEGL-2 0.064 240 AEGL AEGL-2 0.048 480 AEGL AEGL-3 0.67 10 AEGL AEGL-3 0.44 30 AEGL AEGL-3 0.33 60 AEGL AEGL-3 0.19 240 AEGL AEGL-3 0.14 480 AEGL Rat M/F 1 117 7.5 SL Mortality 1/2 Rat M/F 1 117 15 2 Pilerection, red discoloration of fur, blue discoloration of limbs, half-closed eyes, red nasal discharge, mouth breathing, moist or dry rales, apnea, body weight loss (Continued) 265

OCR for page 236
266 TABLE C-1 Continued Source Species Sex No. exposures ppm Minutes Category Effect Rat M/F 1 39 30 2 Clinical signs as above Rat M/F 1 78 30 3 Mortality 2/2 Rat M/F 1 39 42 2 Clinical signs as above Rat M/F 1 78 42 SL Mortality1/2 Rat M/F 1 47 60 2 Clinical signs as above Rat M/F 1 72 60 SL LC50 Rat M/F 1 78 60 3 Mortality 2/2 Rat M/F 1 39 84 SL Mortality 1/2 Rat M/F 1 78 84 3 Mortality 2/2 Rat M/F 1 39 120 SL Mortality 1/2 Rat M/F 1 78 120 3 Mortality 2/2 For category: 0 = no effect, 1 = discomfort, 2 = disabling, SL = some lethality, 3 = lethal