3

Selected Chlorosilanes¹

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 effects. However, the effects are not disabling and are transient and reversible upon cessation of exposure.

¹This document was prepared by the AEGL Development Team composed of Chery Bast (Oak Ridge National Laboratory), Julie M. Klotzbach (Syracuse Research Corporation), and Chemical Manager Ernest V. Falke (National Advisory Committee [NAC] on Acute Exposure Guideline Levels for Hazardous Substances). 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).

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 susceptible 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 susceptible individuals, could experience life-threatening health effects or death.

Airborne concentrations below the AEGL-1 represent exposure concentrations that could produce mild and progressively increasing but transient and nondisabling odor, taste, and sensory irritation or certain asymptomatic, nonsensory 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 levels for the general public, including susceptible subpopulations, such as infants, children, the elderly, persons with asthma, and those with other illnesses, it is recognized that individuals, subject to idiosyncratic responses, could experience the effects described at concentrations below the corresponding AEGL.

SUMMARY

Chlorosilanes contain one or more chlorine atoms covalently bonded to a silicon atom; the maximum chlorine-to-silicon ratio is four. Chlorosilanes are chemical intermediates used in the production of silicone and silicone-containing materials, and are often produced in bulk and transported to manufacturing sites for use. Chlorosilanes are corrosive, and inhalation exposure might cause nasal, throat, or lung irritation, coughing, wheezing, and shortness of breath. Chlorosilanes react rapidly with water, steam, or moisture; hydrolysis yields hydrogen chloride (HCl) gas along with silanols and other condensation products.

The 26 chlorosilanes considered in this chapter are:

Allyl trichlorosilane

Amyl trichlorosilane

Butyl trichlorosilane

Chloromethyl trichlorosilane

Dichlorosilane

Diethyl dichlorosilane

Dimethyl chlorosilane

Dimethyl dichlorosilane

Diphenyl dichlorosilane

Dodecyl trichlorosilane

Ethyl trichlorosilane

Hexyl trichlorosilane

Methyl chlorosilane

Methyl dichlorosilane

Methyl trichlorosilane

Methylvinyl dichlorosilane

Nonyl trichlorosilane

Octadecyl trichlorosilane

Octyl trichlorosilane

Propyl trichlorosilane

Tetrachlorosilane

Trichloro(dichlorophenyl)silane

Trichlorophenylsilane

Trichlorosilane

Trimethyl chlorosilane

Vinyl trichlorosilane

Although chemical-specific toxicity data are not available for many of these chlorosilanes, acute inhalation data from rat studies are available for structurally-similar chlorosilanes (propyl trichlorosilane, methyl trichlorosilane, vinyl trichlorosilane, ethyl trichlorosilane, methylvinyl dichlorosilane, methyl dichlorosilane, dimethyl dichlorosilane, dimethyl chlorosilane, trimethylchlorosilane, and tetrachlorosilane). These data suggest that the acute toxicity of chlorosilanes is largely explained by the HCl hydrolysis product; acute toxicity of these chlorosilanes is qualitatively (based on clinical signs) and quantitatively (based on molar equivalents of HCl) similar to that of HCl (Jean et al. 2006).

On the basis of these data, and in the absence of appropriate chemical-specific data for the chlorosilanes considered in this document, the AEGLs for HCl were used to derive AEGLs for the chlorosilanes. For each class of chloro-silanes (mono-, di-, tri-, and tetra-chlorosilanes), the molar ratio (moles of HCl released per mole of chlorosilane, assuming complete hydrolysis) was used to adjust the AEGL values for HCl to the equivalent concentration of chlorosilane. Detailed information on the derivation of AEGLs for HCl is available in NRC (2004). The calculated values are listed in the Table 3-1.

1. INTRODUCTION

Chlorosilanes contain one or more chlorine atoms covalently bonded to a silicon atom; the maximum chlorine-to-silicon ratio is four. Chlorosilanes are chemical intermediates used in the production of silicone and silicone-containing materials, and are often produced in bulk and transported to manufacturing sites for use.

Chlorosilanes react very rapidly with water, steam, or moisture, releasing HCl gas (AIHA 1998, 1999, 2001a,b,c, 2006). The primary vapor detected in air when chlorosilanes are released is HCl; much less of the parent chlorosilane is detectable (Nakashima et al. 1996; Jean et al. 2006). In an experiment using 11 different chlorosilanes, Jean et al. (2006) reported that the percentage of parent chlorosilane in the test atmosphere ranged from <10% to 58%; other constituents of the atmosphere (in addition to HCl) included silanols and other condensation products. When x-ray microanalysis was performed on air filtered from a dichlorosilane exposure chamber, small (<1 μM in diameter), unidentified particles containing silicon and chloride were detected (Nakashima et al. 1996).

Numerous reports of chlorosilane spills and releases have been received by the U.S. Coast Guard National Response Center. For example, between January 1990 and July 2007, there were 23 reports of dichlorosilane releases ranging from 6 to 2,596 pounds; 32 reports of trichlorosilane releases ranging from 2.6 to 343 pounds; and 14 reports of tetrachlorosilane releases ranging from 2 to 330 pounds (USCG 2007). Releases were from both fixed and mobile sources and were the result of equipment failure and operator error.

TABLE 3-1 Summary of AEGL Values for Selected Chlorosilanes^a

TABLE 3-1

^aValues given in ppm. To convert ppm to mg/m³: (ppm × molecular weight) ÷ 24.5. See Appendix A for the appropriate molecular weight. For mono-, di-, and tri-chlorosilanes not listed, use of HCl equivalents may be considered for AEGL-value derivation.

The chlorosilanes have pungent irritating odors, are corrosive, and inhalation exposure might cause nasal, throat, or lung irritation, coughing, wheezing, and shortness of breath. Although chemical-specific toxicity data are not available for many of the chlorosilanes, acute inhalation data from rat studies are available for structurally-similar chlorosilanes (propyl trichlorosilane, methyl trichlorosilane, vinyl trichlorosilane, ethyl trichlorosilane, methylvinyl dichlorosilane, methyl dichlorosilane, dimethyl dichlorosilane, dimethyl chlorosilane, trimethylchlorosilane, and tetrachlorosilane). These data suggest that the acute toxicity of chlorosilanes is from the HCl hydrolysis product; acute toxicity of the chlorosilanes is qualitatively (based on clinical signs) and quantitatively (based on molar equivalents of HCl) similar to that of HCl (Jean et al. 2006) (see Section 4.3).

On the basis, and in the absence of adequate chemical-specific data for the chlorosilanes considered in this document, the AEGL values for HCl (NRC 2004) were used to obtain AEGL values for the chlorosilanes. The molar ratio (moles HCl released per mole of chlorosilane, assuming complete hydrolysis) was used to adjust the AEGL values for HCl to the equivalent concentration of chlorosilane. Available physicochemical data for the 26 chlorosilanes covered in this chapter are presented in Appendix A.

2. HUMAN TOXICITY DATA

An accidental release of tetrachlorosilane at a chemical plant in a south San Francisco industrial park provided some human exposure data (Kizer et al. 1984). A delivery truck taking a short-cut through a chemical plant hit the tank-coupling unit of a tetrachlorosilane storage tank. The pipeline ruptured and the tetrachlorosilane liquid spilled onto the moist ground; it hydrolyzed rapidly and formed a large gray-white cloud that quickly spread. Workers were unable to stop the leak because the valve was behind a wire enclosure, and approximately 1,200 gallons of tetrachlorosilane was released before the leak was stopped several hours later. By that time, the cloud had risen 500 feet and had spread more than a mile over the industrial park. Five- to ten-thousand employees from 600 businesses over 3 square miles were evacuated. Twenty-eight people reported to local hospitals for treatment of eye or airway irritation. Seven of the patients were employees at the chemical plant, and six of them were smokers. The remaining 21 patients were firemen, policemen, passersby, and employees of other companies in the area. There were no deaths, and no one was hospitalized. Six of the chemical plant employees were referred for further evaluation; these employees were all male, ranged in age from 25 to 56, and were all smokers. Their exposures ranged from 10 to 20 min in duration. Symptoms generally resolved within 24 h, and included lacrimation, rhinorrhea, burning of the mouth and throat, headache, coughing, and wheezing. Pulmonary function tests were normal except that mild obstructive airway disease was noted in four patients. However, it was unclear if the disease was from exposure to tetrachlorosilane or

related to smoking status. Two patients also complained of pedal dysesthesias after the accident. No air concentrations of tetrachlorosilane or HCl were reported.

Reactive airways dysfunction syndrome is an asthma-like condition that develops after a single exposure to high concentrations of a chemical irritant, and has been described after exposure to HCl. Symptoms occur within minutes to hours after the initial exposure and can persist as nonspecific bronchial hyper-responsiveness for months to years (Bernstein 1993). Promisloff et al. (1990) reported reactive airways dysfunction syndrome in three male police officers (36-45 years of age) who responded to a roadside chemical spill. The subjects were exposed to unquantified amounts of sodium hydroxide, tetrachlorosilane, and HCl as a byproduct of trichlorosilane hydrolysis. Because of the mixture of irritants involved in the release, it is probable that all of the compounds contributed to the syndrome observed after this accident.

3. ANIMAL TOXICITY DATA

3.1. Acute Toxicity

One-hour LC₅₀ (lethal concentration, 50% lethality) studies were conducted for 10 chlorosilanes: tetrachlorosilane, propyl trichlorosilane, vinyl trichlorosilane, methyl trichlorosilane, ethyl trichlorosilane, methylvinyl dichlorosilane, dimethyl dichlorosilane, methyl dichlorosilane, trimethyl chlorosilane, and dimethyl chlorosilane (Jean et al. 2006). In each study, groups of five male and five female Fischer 344 rats were exposed to varying concentrations of a chlorosilane for 1 h and observed for up to 14 days. The studies appeared to conform to Good Laboratory Practices and were well-described. The authors used nominal concentrations to calculate LC₅₀ values because chlorosilanes react rapidly with moisture to produce HCl and other hydrolysis products. Using actual chamber concentrations of chlorosilanes would only reflect toxicity of the parent compound, not the toxicity of the parent compound and hydrolysis products. There was agreement between the electrolytic conductivity detector and the nominal concentrations, indicating efficient vaporization of the test material.

Clinical signs were consistent with HCl exposure and included lacrimation, salivation, dried material around the eyes or nose, green staining around the nose and mouth, and perineal urine staining. Labored breathing, rales, hypoactivity, closed or partially closed eyes, prostration, corneal opacity or opaqueness, and swollen or necrotic paws also were observed. Hemorrhage, congestion, and consolidation of the lungs; ectasia of the lungs; gaseous distension of the gastrointestinal tract; absence of body fat; obstruction of nostrils; dried or firm nares; alopecia around the eyes; and discoloration of hair were observed at necropsy. Mortality data and LC₅₀ values from 1-h exposure studies with rats are summarized in Table 3-2.

TABLE 3-2 Mortality Data and LC₅₀ Values from 1-Hour Exposure Studies

^aProbit analysis.

^bSpearman-Karber analysis.

Source: Jean et al. 2006. Reprinted with permission; copyright 2006, Inhalation Toxicology.

In another study, groups of 10 male ICR mice were exposed for 4 h to nominal concentrations of dichlorosilane at 49-259 ppm, followed by a 14-day observation period (Nakashima et al. 1996). Mortality was 0/10, 0/10, 1/10, 6/10, 4/10, 10/10, 10/10, 9/10, and 10/10 for groups exposed at 0, 49, 100, 131, 141, 199, 216, 218, and 259 ppm, respectively. An LC₅₀ of 144 ppm was calculated.

3.2. Developmental and Reproductive Toxicity

No data on developmental or reproductive toxicity were found.

3.3. Genotoxicity

The only genotoxicity data found were for tetrachlorosilane. Tetrachlorosilane was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA 1535, TA1537, or TA1538; Saccharomyces cerevisiae strain D-4; or Escherischia coli strains W3110/polA⁺ and P3478/polA^- either with or without metabolic activation. It was also negative in a L5178Y mouse lymphoma assay (AIHA 1999).

3.4. Chronic Toxicity and Carcinogenicity

No data on chronic toxicity or carcinogenicity were found.

3.5. Summary

Although toxicity data are sparse for individual chlorosilanes, well-conducted 1-h inhalation toxicity studies in rats are available for a series of chlorosilanes (Jean et al. 2006). In general, LC₅₀ values for monochlorosilanes were approximately twice the LC₅₀ values for dichlorosilanes and three times the LC₅₀ values for trichlorosilanes. Tetrachlorosilane had an LC₅₀ value similar to the trichlorosilanes; however, there were experimental difficulties at the lowest concentration tested. Clinical signs were indicative of severe irritation or corrosion. The evidence suggests that the acute toxicity of chlorosilanes is largely attributable to the release of HCl; however, no information on the identity or potential toxicity of other decomposition products was found. No data concerning developmental or reproductive toxicity, genotoxicity, or carcinogenicity for exposure to the chlorosilanes were found in the literature.

4. SPECIAL CONSIDERATIONS

4.1. Metabolism and Disposition

No information was found concerning the metabolism and disposition of chlorosilanes.

4.2. Mechanism of Toxicity

Chlorosilanes react violently with water to produce HCl gas (AIHA 1998, 1999, 2001a,b,c, 2006). In an experiment using 11 different chlorosilanes, Jean et al. (2006) reported that the percentage of parent chlorosilane in the test atmosphere range from <10 to 58%; other constituents of the atmosphere (in addition to HCl) included silanols and other condensation products. Nakashima et al. (1996) reported that small particles containing silicon and chlorine were detected in an inhalation exposure chamber into which dichlorosilane was introduced; the identity and quantity of particles were not reported. IPCS (2002a) reported that, when heated, trimethylchlorosilane decomposition could release HCl and phosgene. No other information on potential decomposition products of chlorosilanes was found. Available data suggest that the acute toxicity of chlorosilanes is largely from the HCl hydrolysis product; acute toxicity of the chlorosi-lanes is qualitatively (based on clinical signs) and quantitatively (based on molar equivalents of HCl) similar to that of HCl.

4.3 Structure Activity Relationships

A 1-h LC₅₀ study with HCl was performed in rats and used for comparison with the chlorosilane 1-h LC₅₀ values (Jean et al. 2006). According to the authors, the study with HCl was unpublished, but was performed in the same laboratory and was conducted using the same protocol as that used in the chlorosilane study (1-h whole-body exposure with a 14-day recovery period). Five rats per sex were exposed to HCl at 0, 2,456, 3,236, or 4,210 ppm for 1 h and observed for up to 14 days. Chamber concentrations were determined by a Fourier transform infrared spectrophotometer analyzer. Clinical signs included labored breathing; gasping; emaciation; rough coat; lethargy; corneal opacity; crusting, necrotic, discolored, and blocked nares or nasal opening; paws with missing, necrotic, or swollen digits; and weight loss. Gross pathology of animals dying during the study included irritation and necrosis of most extremities, severe respiratory-tract injuries, and corneal opacity. A 1-h LC₅₀ of 3,627 ppm was calculated for HCl.

The LC₅₀ data obtained for the chlorosilanes showed a strong association with chlorine content for the mono-, di-, and tri-chlorosilanes. In general, LC₅₀ values for monochlorosilanes were approximately twice the LC₅₀ values for dichlorosilanes and three times the LC₅₀ values for trichlorosilanes. Tetrachlorosilane exhibited an LC₅₀ value similar to the trichlorosilanes.

The predicted 1-h LC₅₀ values for the chlorosilanes, based on HCl equivalents, are presented in Table 3-3. The predicted values for the chlorosilanes are comparable to the experimentally-derived 1-h LC₅₀ values (log * log regression analysis of chlorosilane LC₅₀ values vs. the number of chlorine groups yielded an r² value of 0.97). The data suggest that the acute toxicity of the chlorosilanes is similar to or slightly less than what would be expected based on HCl molar

equivalents. The within-class LC₅₀ values were not significantly influenced by the number or type of hydrocarbon R-group(s) present (methyl, ethyl, propyl, or vinyl). Cases where the predicted value is less might be attributed to incomplete hydrolysis in the test atmosphere; however, continued hydrolysis and generation of HCl would be expected for any remaining chlorosilane when in contact with moist tissues (mucous membranes, lung) (Jean et al. 2006). This information taken in conjunction with the observed clinical signs suggests that the acute toxicity of the chlorosilanes is quantitatively and qualitatively similar to HCl and that the HCl hydrolysis product is responsible for the acute toxicity of the chlorosilanes.

TABLE 3-3 Measured and Predicted 1-Hour LC₅₀ Values for Selected

The 4-h mouse LC₅₀ of 144 ppm for dichlorosilane (Nakashima et al. 1996) also supports the conclusion that the acute inhalation toxicity of chlorosilanes is from the HCl hydrolysis product. The reported 1-h mouse LC₅₀ for HCl is 1,108 ppm (NRC 2004). Scaling across time for HCl may be accomplished using the equation Cⁿ × t = k, where n = 1 based on regression analysis of combined rat and mouse LC₅₀ data (1-100 min) (NRC 2004). Scaling the 1-h LC₅₀ value for HCl of 1,108 ppm to a 4-h period yields an approximate 4-h LC₅₀ value of 277 ppm. Dividing this 4-h LC₅₀ by a molar adjustment factor of 2, yields a predicted LC₅₀ of 139 ppm for dichlorosilane, which is similar to the experimentally-derived value of 144 ppm.

The 26 chlorosilanes addressed in this chapter include those with alkane, alkene, aromatic, and chlorinated substituents. Although the evidence from Jean et al. (2006) suggests that the acute toxicity is from HCl formed as a hydrolysis product, the data were generated using 11 of the 26 chlorosilanes, including primarily alkane-subsituted compounds and two of the three compounds with alkene substituent groups. Of the 26, two have aromatic substituents and two (including one of the aromatics) have chlorinated substituents; none of those was among the tested compounds.

4.4. Other Relevant Information

4.4.1. Species Variability

Data were not available regarding species variability in lethal and nonlethal toxicity from chlorosilane exposure. Differences in response to HCl have been observed between primates and rodents. Rodents exhibit sensory and respiratory irritation after exposure to high concentrations of HCl. Concentration-dependent decreases in respiratory frequency indicative of a protective mechanism are observed in rodents, whereas baboons exposed at 500, 5,000, or 10,000 ppm exhibited concentration-dependent increases in respiratory frequency indicative of a compensatory response to hypoxia and a possible increase in the total dose delivered to the lung (NRC 1991). Kaplan et al. (1988) found that five of six mice died when exposed to HCl at 2,550 ppm for 15 min, but no baboons died when exposed at 10,000 ppm for 15 min. The LC₅₀ values reported by Darmer et al. (1974), Wohlslagel et al. (1976), and Higgins et al. (1972) indicate that mice are approximately three times more sensitive than rats to HCl. Guinea pigs also appear to be more sensitive than rats to HCl; however, the guinea pig studies have provided conflicting results. For respiratory irritants such as HCl, the mouse “may not be a good model for extrapolation to humans,” because “mice appear to be much more susceptible to the lethal effects of HCl than other rodents or baboons. To some extent, this increased susceptibility may be due to less effective scrubbing of HCl in the upper respiratory tract” (NRC 1991).

Because most rodents are obligatory nose breathers whereas humans may be mouth breathers, especially during exercise, Stavert et al. (1991) studied the effects of inhaling HCl through the nose and mouth in rats. HCl was delivered directly to the trachea by cannulation. Higher mortality rates occurred with orally-cannulated rats compared with rats exposed by nose. Tracheal necrosis and inflammatory-cell accumulation were found in cannulated rats, whereas effects in nose-breathing rats were confined to the nasal passages. These results indicate that the site of injury and resultant toxicologic effects differ with oral or nasal breathing, with the former mode resulting in more severe responses under similar exposure situations.

4.4.2. Susceptible Populations

No information was available on populations that might be especially sensitive to chlorosilane or HCl. However, clinical signs of chlorosilane and HCl exposure are consistent with contact irritation. In general, contact-irritant effects are not expected to vary widely among individuals. However, as noted by NRC (2004), asthmatic persons and others with sensitive airways might be more susceptible to the effects of HCl inhalation.

On the basis of the study by Stavert et al. (1991), which showed more severe respiratory responses to HCl in orally-cannulated rats compared with nose-breathing rats, it is possible that persons who habitually breathe orally might experience more pronounced or different health effects than those who primarily breathe nasally. Likewise, physical exertion might intensify the respiratory effects of HCl or chlorosilane exposure as individuals shift from nasal to oral breathing during exertion.

5. DATA ANALYSIS FOR AEGL-1

5.1. Summary of Human Data Relevant to AEGL-1

No human data relevant to development of AEGL-1 values were found.

5.2. Summary of Animal Data Relevant to AEGL-1

No animal data relevant to development of AEGL-1 values were found.

5.3. Derivation of AEGL-1

AEGL-1 values for the chlorosilanes were determined by modifying the AEGL-1 values that were established for HCl. The use of HCl as a surrogate for chlorosilanes was deemed appropriate because adverse effects from exposure to chlorosilanes have been attributed to their hydrolysis product, HCl. The AEGL-1 values for HCl were based on a no-observed-adverse-effect level in exercising adult with asthma (NRC 2004). The same AEGL-1 value was applied across all

specified exposure periods, because mild irritation generally does not vary greatly over time and because prolonged exposure is not expected to result in an enhanced effect (NRC 2004). The key study and calculations used to determine the AEGL-1 values for HCl are summarized in Appendixes C and E (more detail is available in the technical support document for HCl published in NRC [2004]). The molar ratio (moles of HCl released per mole of chlorosilane, assuming complete hydrolysis) was used to adjust the AEGLs for HCl to the equivalent concentration of chlorosilane. Although the 1-h rat LC₅₀ value for tetrachlorosilane suggests that only 3 moles of HCl were produced, the use of a molar adjustment factor of 4 is considered appropriate because of experimental difficulties that occurred at lower exposure concentrations in this study. The use of the molar adjustment factor of 4 will yield protective AEGL values and is consistent with the approach taken for the overall chlorosilane database. The AEGL-1 values for the chlorosilanes are presented in Table 3-4, and their calculations are presented in Appendix B.

TABLE 3-4 AEGL-1 Values for Selected Chlorosilanes^a

^aValues given in ppm. To convert ppm to mg/m³: (ppm × molecular weight) ÷ 24.5. See Appendix A for the appropriate molecular weight.

6.3. Derivation of AEGL-2

AEGL-2 values for the chlorosilanes were determined by modifying the AEGL-2 values that were established for HCl. The use of HCl as a surrogate for chlorosilanes was deemed appropriate because adverse effects from exposure to chlorosilanes have been attributed to their hydrolysis product, HCl. AEGL-2 values for HCl were based on severe nasal or pulmonary histopathologic changes in rats (exposed for 30 min to 8 h) or a modification of the mouse 50% respiratory rate decrease (RD₅₀) (exposed for 10 min) (NRC 2004). The key study and calculations used to determine the AEGL-2 values for HCl are summarized in Appendixes C and E (more detail is available in the technical support document for HCl published in NRC [2004]). The molar ratio (moles of HCl released per mole of chlorosilane, assuming complete hydrolysis) was used to adjust the AEGLs for HCl to the equivalent concentration of chlorosilane. The AEGL-2 values for the chlorosilanes are presented in Table 3-5, and their calculations are presented in Appendix B.

7. DATA ANALYSIS FOR AEGL-3

7.1. Summary of Human Data Relevant to AEGL-3

No human data relevant to development of AEGL-3 values were found.

7.2. Summary of Animal Data Relevant to AEGL-3

One-hour rat LC₅₀ values were reported by Jean et al. (2006) to be 4,478 ppm for dimethyl dichlorosilane and 2,021 ppm for methylvinyl dichlorosilane. One-hour rat LC₅₀ values for trichlorsilanes were 1,257, 1,352, and 1,611 ppm for ethyl trichlorosilane, propyl trichlorosilane, and vinyl trichlorosilane, respectively (Jean et al. 2006). A 1-h rat LC₅₀ value of 1,312 ppm was reported for tetrachlorosilane (Jean et al. 2006). A 4-h mouse LC₅₀ value of 144 ppm was reported for dichlorosilane (Nakashima et al. 1996), but the mouse is considered to be an unreliable model for the acute toxicity of HCl in humans (NRC 1991, 2004). No animal data relevant to development of AEGL-3 values were found for the other chlorosilanes.

7.3. Derivation of AEGL-3

AEGL-3 values for the chlorosilanes were determined by modifying the AEGL-3 values that were established for HCl. The use of HCl as a surrogate for chlorosilanes was deemed appropriate because adverse effects from exposure to chlorosilanes have been attributed to their hydrolysis product, HCl. The AEGL-3 values for HCl were based on a 1-h rat LC₅₀ value divided by 3 to estimate a lethality threshold (NRC 2004). The key study and calculations used to determine the AEGL-3 values for HCl are summarized in Appendixes C and E (more detail

is available in the technical support document for HCl published in NRC [2004]). The molar ratio (moles of HCl released per mole of chlorosilane, assuming complete hydrolysis) was used to adjust the AEGLs for HCl to the equivalent concentration of chlorosilane. The AEGL-2 values for the chlorosilanes are presented in Table 3-6, and their calculations are presented in Appendix B.

8. SUMMARY OF AEGLS

8.1. AEGL Values and Toxicity End Points

AEGL values for selected chlorosilanes are summarized in Table 3-7. Derivation summary tables appear in Appendix E, and category plots for the selected chlorosilanes are in Appendix F. AEGL values were based on molar adjustments of the AEGL values for HCl. For mono-, di-, and tri- chlorosilanes not listed, use of HCl equivalents may be considered for AEGL-value derivation.

TABLE 3-5 AEGL-2 Values for Selected Chlorosilanes^a

^aValues given in ppm. To convert ppm to mg/m³: (ppm × molecular weight) ÷ 24.5. See Appendix A for the appropriate molecular weight.

TABLE 3-6 AEGL-3 Values for Selected Chlorosilanes

^aValues given in ppm. To convert ppm to mg/m³: (ppm × molecular weight) ÷ 24.5. See Appendix A for the appropriate molecular weight.

8.2. Comparison with Other Standards and Guidelines

There are no standards or guidelines for most of the chlorosilanes considered in this chapter. The few guidelines available are Emergency Response Planning Guidelines (ERPGs) and Workplace Environmental Exposure Level (WEEL) ceiling levels for trimethylchlorosilane, dimethyl dichlorosilane, trichlorosilane, methyl trichlorosilane, vinyl trichlorosilane, and tetrachlorosilane. Available standards and guidelines are presented in Tables 3-8. The available ERPG values are comparable to the AEGLs derived herein.

TABLE 3-7 Summary of AEGL Values for Selected Chlorosilanes^a

TABLE 3-7

^aValues given in ppm. To convert ppm to mg/m³: (ppm × molecular weight) ÷ 24.5. See Appendix A for the appropriate molecular weight.

TABLE 3-8 Extant Standards and Guidelines for Selected Chlorosilanes

TABLE 3-8

^aERPG (Emergency Response Planning Guidelines, American Industrial Hygiene Association) (AIHA 2010).

ERPG-1 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to 1 h without experiencing effects other than mild, transient adverse health effects or without perceiving a clearly defined objectionable odor. An ERPG-1 was not derived because of insufficient data. ERPG-2 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to 1 h without experiencing or developing irreversible or other serious health effects or symptoms that could impair an individual’s ability to take protective action. The ERPG-2 for BCME is based on animal data, and was intended to be below 0.21 ppm, which was calculated to have a 1 × 10^-4 excess carcinogenicity risk, and 0.7 ppm, which caused serious respiratory lesions in animals. ERPG-3 is the maximum airborne concentration below which it is believed nearly all individuals could be exposed for up to 1 h without experiencing or developing life-threatening health effects. The ERPG-3 for BCME is based on animal lethality data. ^bWEEL (Workplace Environmental Exposure Level, American Industrial Hygiene Association) (AIHA 2010).

WEELs are health-based values, expressed as either time-weighted average (TWA) concentrations or ceiling values believed to provide guidance for protection of most workers exposed as a result of their occupations. A WEEL ceiling value is the instantaneous concentration that should not be exceeded at any time during the workday to prevent acute adverse health effects or discomfort.

8.3. Data Adequacy and Research Needs

There are no human or animal data on chlorosilanes relevant to AEGL-1 health end points. Likewise, there are no appropriate human data and few animal data relevant to AEGL-2 end points. A single study (Jean et al. 2006) that estimated LC₅₀ values for 11 of the 26 chlorosilanes considered in this chapter provided data on lethality (an AEGL-3 end point). This study also supports the inference that the hydrolysis product, HCl, is largely responsible for the acute

inhalation toxicity of the chlorosilanes. There is anecdotal information on other hydrolysis and decomposition products (Nakashima et al. 1996). However, no information on the chemical form, physiological disposition, or potential toxicity of these decomposition products was found. Additional research on the identity and potential toxicity of decomposition products would enhance confidence in the database.

The available data on chlorosilane toxicity is limited to 11 of the 26 compounds addressed herein, and there were no data on chlorosilanes with aromatic or chlorinated substituents. The lack of data on the contribution of aromatic or chlorinated substituents to the toxicity of the chlorosilanes introduces uncertainty with respect to the protection afforded by using the molar equivalent of AEGL values for HCl as a surrogate for the AEGLs estimated for diphenyl dichlorosilane, trichloro(dichlorophenyl)silane, and trichlorophenylsilane. Additional research would enhance confidence in the AEGLs for these compounds.

The database on HCl was described by NRC (2004, pp. 107-109) as follows:

Human data are limited to one study showing no significant effects in asthmatic subjects and to dated anecdotal information. Furthermore, the involvement of [reactive airway dysfunction syndrome] in HCl toxicity is unclear. Many more data are available for animal exposures; however, many of those studies used compromised animals or very small experimental groups, resulting in limited data for many species but no in-depth database for a given species. Also, some studies involve very short exposures to high concentrations of HCl. Thus, confidence in the AEGL values is at best moderate.

One important area of uncertainty is the role of ambient humidity on the release of HCl and the toxicity of chlorosilanes. The LC₅₀ values reported by Jean et al. (2006), and used as the basis for concluding that the toxicity of chlorosilanes is well-predicted by HCl content, were obtained at a relative humidity of 35%. Higher humidity would probably have increased the degree of hydrolysis, resulting in higher HCl concentrations and lower concentrations of parent compound; whether this would affect the lethal concentrations is unknown and merits additional research.

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APPENDIX A

PHYSICAL AND CHEMICAL PROPERTIES OF SELECTED CHLOROSILANES

TABLE A-1 Chemical and Physical Properties for Allyl Trichlorosilane

TABLE A-2 Chemical and Physical Properties for Amyl Trichlorosilane

TABLE A-3 Chemical and Physical Properties for Butyl Trichlorosilane

TABLE A-4 Chemical and Physical Properties for Chloromethyl

TABLE A-5 Chemical and Physical Properties for Dichlorosilane

TABLE A-6 Chemical and Physical Properties for Diethyl Dichlorosilane

TABLE A-7 Chemical and Physical Properties for Dimethyl Chlorosilane

TABLE A-8 Chemical and Physical Properties for Diethyl Dichlorosilane

TABLE A-9 Chemical and Physical Properties for Diphenyl Dichlorosilane

TABLE A-10 Chemical and Physical Properties for Dodecyl Trichlorosilane

TABLE A-11 Chemical and Physical Properties for Ethyl Trichlorosilane

TABLE A-12 Chemical and Physical Properties for Hexyl Trichlorosilane

TABLE A-13 Chemical and Physical Properties for Methyl Chlorosilane

TABLE A-14 Chemical and Physical Properties for Methyl Dichlorosilane

TABLE A-15 Chemical and Physical Properties for Methyl Trichlorosilane

TABLE A-16 Chemical and Physical Properties for Methylvinyl Dichlorosilane

TABLE A-17 Chemical and Physical Properties for Nonyl Trichlorosilane

TABLE A-18 Chemical and Physical Properties for Octadecyl Trichlorosilane

TABLE A-19 Chemical and Physical Properties for Octyl Trichlorosilane

TABLE A-20 Chemical and Physical Properties for Propyl Trichlorosilane

TABLE A-21 Chemical and Physical Properties for Tetrachlorosilane

TABLE A-22 Chemical and Physical Properties for Trichloro(dichlorophenyl)silane

TABLE A-23 Chemical and Physical Properties for Trichlorophenylsilane

TABLE A-24 Chemical and Physical Properties for Trichlorosilane

TABLE A-25 Chemical and Physical Properties for Trimethyl Chlorosilane

TABLE A-26 Chemical and Physical Properties for Vinyl Trichlorosilane

APPENDIX B

DERIVATION OF AEGL VALUES FOR SELECTED CHLOROSILANES

Derivation of AEGL-1

APPENDIX C

DERIVATION OF AEGL VALUES FOR HYDROGEN CHLORIDE (NRC 2004)

Derivation of AEGL-1 Values

SUMMARY OF KEY STUDY AND RATIONALE USED TO DERIVE AEGL VALUES FOR HYDROGEN CHLORIDE (Excerpted from NRC 2004)

AEGL-1 Values

Because appropriate human data exist for exposure to HCl, they were used to identify AEGL-1 values. Exposure to HCl at 1.8 ppm for 45 min resulted in a no-observed-adverse-effect level in 10 exercising young adult asthmatic subjects (Stevens et al. 1992). Because exercise will increase HCl uptake and exacerbate irritation, those asthmatic subjects are considered a sensitive subpopulation. Therefore, because the test subjects were a sensitive subpopulation and the end point was essentially a no-effect level, no uncertainty factor was applied to account for sensitive human subpopulations. Adequate human data were available, so no uncertainty factor was applied for animal to human extrapolation. The no-effect level was held constant across the 10- and 30-min and 1-, 4-, and 8-h exposure time periods. That approach was considered appropriate because mild irritant effects generally do not vary greatly over time, and the end point of a no-effect level in a sensitive population is inherently conservative.

AEGL-2 Values

The AEGL-2 for the 30-min and 1-, 4-, and 8-h time points was based on severe nasal or pulmonary histopathology in rats exposed to HCl at 1,300 ppm for 30 min (Stavert et al. 1991). A modifying factor of 3 was applied to account for the relatively sparse database describing effects defined by AEGL-2. The AEGL-2 values were further adjusted by a total uncertainty factor of 10—3 for intraspecies variability, supported by the steep concentration-response curve, which implies little individual variability; and 3 for interspecies variability. Using the default value of 10 for interspecies variability would bring the total adjustment to 100 instead of 30. That would generate AEGL-2 values that are not supported by data on exercising asthmatic subjects, an especially sensitive subpopulation. Exercise increases HCl uptake and exacerbates irritation; no effects were noted in exercising young adult asthmatic subjects exposed to HCl at 1.8 ppm for 45 min (Stevens et al. 1992). Using a total uncertainty factor of 30 would yield 4- and 8-h values of 3.6 ppm (instead of 11 ppm). The prediction that humans would be disabled by exposure for 4 or 8 h to 3.6 ppm cannot be supported when exercising asthmatic subjects exposed to one-half that concentration for 45 min exhibited no effects. The shorter time points would yield values 4 to 7 times the 1.8-ppm value; however, confidence in the time-scaling for HCl is good for times up to 100 min, because the value of n was derived from a regression analysis of rat and mouse mortality data with exposure durations ranging from 1 min to 100 min. The 30-min value of 43 ppm derived with a total uncertainty factor of 10 is reasonable in light of the fact that baboons exposed at

500 ppm for 15 min experienced only a slightly increased respiratory rate. Therefore, a total uncertainty factor of 10, accompanied by the modifying factor of 3, is most consistent with the database. Thus, the total factor is 30. Time-scaling for the 1-h AEGL exposure period used the Cⁿ × t = k relationship, where n = 1 based on regression analysis of combined rat and mouse LC₅₀ data (1 to 100 min) as reported by ten Berge et al. (1986). The 4- and 8-h AEGL-2 values were derived by applying a modifying factor of 2 to the 1-h AEGL-2 value, because time-scaling would yield a 4-h AEGL-2 of 5.4 ppm and an 8-h AEGL-2 of 2.7 ppm, close to the 1.8 ppm tolerated by exercising asthmatic subjects without observed adverse health effects. Repeated-exposure rat data suggest that the 4- and 8-h values of 11 ppm are protective. Rats exposed to HCl at 10 ppm for 6 h/day, 5 days/week for life exhibited only tracheal and laryngeal hyperplasia, and rats exposed to HCl at 50 ppm for 6 h/day, 5 days/week for 90 days exhibited only mild rhinitis.

The 10-min AEGL-2 was derived by dividing the mouse RD₅₀ of 309 ppm by a factor of 3 to obtain a concentration causing irritation (Barrow et al. 1977). It has been determined that human response to sensory irritants can be predicted on the basis of the mouse RD₅₀. For example, Schaper (1993) has validated the correlation of 0.03 × RD₅₀ = TLV (threshold limit value) as a value that will prevent sensory irritation in humans. The 0.03 represents the half-way point between 0.1 and 0.01 on a logarithmic scale, and Alarie (1981) has shown that the RD₅₀ multiplied by 0.1 corresponds to “some sensory irritation,” whereas the RD₅₀ value itself is considered “intolerable to humans.” Thus, it is reasonable that one-third of the RD₅₀, a value half-way between 0.1 and 1 on a logarithmic scale, might cause significant irritation to humans. Furthermore, one-third of the mouse RD₅₀ for HCl corresponds to an approximate decrease in respiratory rate of 30%, and decreases in the range of 20-50% correspond to moderate irritation (ASTM 1991).

AEGL-3 Values

The AEGL-3 was based on a 1-h rat LC₅₀ study (Wohlslagel et al. 1976; Vernot et al. 1977). One-third of the 1-h LC₅₀ value of 3,124 ppm was used as an estimated concentration causing no deaths. That estimate is inherently conservative (no deaths observed in the same study at 1,813 ppm). A total uncertainty factor of 10 will be applied—3 for intraspecies variation, because the steep concentration-response curve implies limited individual variability; and 3 to protect susceptible individuals. Using a full value of 10 for interspecies variability (total uncertainty factor of 30) would yield AEGL-3 values that are inconsistent with the overall data set.

A number of factors argue for the use of an uncertainty factor of 10 instead of 30, they are: (1) the steep concentration-response curve for lethality observed in the Wohlslagel et al. (1976) study in which the estimated LC₀ (one-third of the LC₅₀ of 3,124 ppm) is lower than the experimental LC₀ of 1,813

ppm. The LC₀ selection is conservative, and the steep concentration-response curve argues for little interindividual variability; (2) AEGL-3 values generated from a total uncertainty factor of 30 would be close (within a factor of 2) to the AEGL-2 values generated from data on exercising asthmatic subjects; (3) Sella-kumar et al. (1985) exposed rats to HCl at 10 ppm for 6 h/day, 5 days/week for life and only observed increased trachael and laryngeal hyperplasia. The estimated 6-h AEGL-3 using an intraspecies uncertainty factor of 3 is 17 ppm, close to the concentration inhaled in the lifetime study in which only mild effects were induced; and (4) rats exposed to HCl at 50 ppm for 6 h/day, 5 days/week for 90 days exhibited mild rhinitis (Toxigenics Inc. 1984). This level is already twice the AEGL-3 value, which is intended to protect against death.

Thus, the total uncertainty factor was set at 10. It was then time-scaled to the specified 10- and 30-min and 4-h AEGL exposure periods using the Cⁿ × t = k relationship, where n = 1 based on regression analysis of combined rat and mouse LC₅₀ data (1 min to 100 min) as reported by ten Berge et al. (1986). The 4-h AEGL-3 also was adopted as the 8-h AEGL-3 because of the uncertainty of time-scaling to 8 h with an n value derived from exposure durations of up to 100 min.

The 5-min rat LC₀ of 30,000 ppm (Higgins et al. 1972) supports the 10-min AEGL-3 value. Extrapolating that value across time (n = 1) to 10 min and applying an uncertainty factor of 10 yields a value of 1,500 ppm, suggesting that the proposed AEGL-3 value is protective. Also, if the 5-min rat LC₅₀ of 41,000 ppm for HCl vapor (Darmer et al. 1974) is divided by 3 to estimate a no-effect level for death, extrapolated to 10 min, and an uncertainty factor of 10 is applied, a supporting value of 683 ppm is obtained.

APPENDIX D

ACUTE EXPOSURE GUIDELINE LEVELS FOR SELECTED CHLOROSILANES

Derivation Summary

AEGL-1 VALUES FOR MONOCHLOROSILANES

AEGL-1 VALUES FOR TRICHLOROSILANES

AEGL-1 VALUES FOR TRICHLOROSILANES

Key reference: NRC (National Research Council). 2004. Hydrogen chloride. Pp. 77-122 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: National Academies Press.

End point/Concentration/Rationale: AEGL-1 values for trichlorosilanes were derived by adjusting the AEGL-1 values for HCl by the molar ratio of HCl to trichlorosilanes. This approach is considered reasonable because qualitative and quantitative data on chlorosilanes suggest that the HCl hydrolysis product is largely responsible for the acute toxicity of the chlorosilanes.

Molar Adjustment Factor: 3

Data adequacy: Mechanism-of-action data were considered adequate for the derivation of AEGL-1 values for chlorosilanes based on analogy to HCl. Confidence in the AEGL-1 values for chlorosilanes is low, reflecting the lack of data on AEGL-1 end points after chlorosilane exposure and reliance on HCl data. Additional research on AEGL-1 effects of chlorosilanes would reduce uncertainty.

AEGL-1 VALUES FOR TETRACHLOROSILANE

Key reference: NRC (National Research Council). 2004. Hydrogen chloride. Pp. 77-122 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: National Academies Press.

End point/Concentration/Rationale: AEGL-1 values for tetrachlorosilane were derived by adjusting the AEGL-1 values for HCl by the molar ratio of HCl to tetrachlorosilane. This approach is considered reasonable because qualitative and quantitative data on chlorosilanes suggest that the HCl hydrolysis product is largely responsible for the acute toxicity of the chlorosilanes.

Molar adjustment factor: 4

Data adequacy: Mechanism-of-action data were considered adequate for the derivation of AEGL-1 values for chlorosilanes based on analogy to HCl. Confidence in the AEGL-1 values for chlorosilanes is low, reflecting the lack of data on AEGL-1 end points after chlorosilane exposure and reliance on HCl data. Additional research on AEGL-1 effects of chlorosilanes would reduce uncertainty.

AEGL-2 VALUES FOR MONOCHLOROSILANES

Key reference: NRC (National Research Council). 2004. Hydrogen chloride. Pp. 77-122 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: National Academies Press.

End point/Concentration/Rationale: AEGL-2 values for HCl were adopted as AEGL-2 values for monochlorosilanes. This approach is considered reasonable because qualitative and quantitative data on chlorosilanes suggest that the HCl hydrolysis product is largely responsible for the acute toxicity of the chlorosilanes.

Data adequacy: Mechanism-of-action data were considered adequate for the derivation of AEGL-2 values for chlorosilanes based on analogy to HCl. Confidence in the AEGL-2 values for chlorosilanes is moderate, reflecting the limited data on AEGL-2 end points after chlorosilane exposure and reliance on HCl data. Additional research on AEGL-2 effects of chlorosilanes would reduce uncertainty.

AEGL-2 VALUES FOR DICHLOROSILANES

Key reference: NRC (National Research Council). 2004. Hydrogen chloride. Pp. 77-122 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: National Academies Press.

End point/Concentration/Rationale: AEGL-2 values for dichlorosilanes were derived by adjusting the AEGL-2 values for HCl by the molar ratio of HCl to dichlorosilane. This approach is considered reasonable because qualitative and quantitative data on chlorosilanes suggest that the HCl hydrolysis product is largely responsible for the acute toxicity of the chlorosilanes.

Molar adjustment factor: 2

Data adequacy: Mechanism-of-action data were considered adequate for the derivation of AEGL-2 values for chlorosilanes based on analogy to HCl. Confidence in the AEGL-2 values for chlorosilanes is moderate, reflecting the limited data on AEGL-2 end points after chlorosilane exposure and reliance on HCl data. Additional research on AEGL-2 effects of chlorosilanes would reduce uncertainty.

AEGL-2 VALUES FOR TRICHLOROSILANES

Key reference: NRC (National Research Council). 2004. Hydrogen chloride. Pp. 77-122 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: National Academies Press.

End point/Concentration/Rationale: AEGL-2 values for trichlorosilanes were derived by adjusting the AEGL-2 values for HCl by the molar ratio of HCl to trichlorosilane. This approach is considered reasonable because qualitative and quantitative data on chlorosilanes suggest that the HCl hydrolysis product is largely responsible for the acute toxicity of the chlorosilanes.

Molar adjustment factor: 3

Data adequacy: Mechanism-of-action data were considered adequate for the derivation of AEGL-2 values for chlorosilanes based on analogy to HCl. Confidence in the AEGL-2 values for chlorosilanes is moderate, reflecting the limited data on AEGL-2 end points after chlorosilane exposure and reliance on HCl data. Additional research on AEGL-2 effects of chlorosilanes would reduce uncertainty.

AEGL-2 VALUES FOR TETRACHLOROSILANE

Key reference: NRC (National Research Council). 2004. Hydrogen chloride. Pp. 77-122 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: National Academies Press.

End point/Concentration/Rationale: AEGL-2 values for tetrachlorosilane were derived by adjusting the AEGL-2 values for HCl by the molar ratio of HCl to tetrachlorosilane. This approach is considered reasonable because qualitative and quantitative data on chlorosilanes suggest that the HCl hydrolysis product is largely responsible for the acute toxicity of the chlorosilanes.

Molar adjustment factor: 4

Data adequacy: Mechanism-of-action data were considered adequate for the derivation of AEGL-2 values for chlorosilanes based on analogy to HCl. Confidence in the AEGL-2 values for chlorosilanes is moderate, reflecting the limited data on AEGL-2 end points after chlorosilane exposure and reliance on HCl data. Additional research on AEGL-2 effects of chlorosilanes would reduce uncertainty.

AEGL-3 VALUES FOR MONOCHLOROSILANES

Key reference: NRC (National Research Council). 2004. Hydrogen chloride. Pp. 77-122 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: National Academies Press..

End point/Concentration/Rationale: AEGL-3 values for HCl were adopted as AEGL-3 values for monochlorosilanes. This approach is considered reasonable because qualitative and quantitative data on chlorosilanes suggest that the HCl hydrolysis product is largely responsible for the acute toxicity of the chlorosilanes.

Data adequacy: Data were considered adequate for the derivation of AEGL-3 values for chlorosilanes based on analogy to HCl. Confidence in the AEGL-3 values for chlorosilanes is high, reflecting the availability of lethality data on 11 of the 26 chlorosilanes considered and evidence for the role of HCl as the proximate toxicant. No additional research is needed on AEGL-3 end points.

AEGL-3 VALUES FOR DICHLOROSILANES

Key reference: NRC (National Research Council). 2004. Hydrogen chloride. Pp. 77-122 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: National Academies Press.

End point/Concentration/Rationale: AEGL-3 values for dichlorosilanes were derived by adjusting the AEGL-3 values for HCl by the molar ratio of HCl to dichlorosilane. This approach is considered reasonable because qualitative and quantitative data on chlorosilanes suggest that the HCl hydrolysis product is largely responsible for the acute toxicity of the chlorosilanes.

Molar adjustment factor: 2

Data adequacy: Data were considered adequate for the derivation of AEGL-3 values for chlorosilanes based on analogy to HCl. Confidence in the AEGL-3 values for chlorosilanes is high, reflecting the availability of lethality data on 11 of the 26 chlorosilanes considered and evidence for the role of HCl as the proximate toxicant. No additional research is needed on AEGL-3 end points.

AEGL-3 VALUES FOR TRICHLOROSILANES

Key reference: NRC (National Research Council). 2004. Hydrogen chloride. Pp. 77-122 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: National Academies Press.

End point/Concentration/Rationale: AEGL-3 values for trichlorosilanes were derived by adjusting the AEGL-3 values for HCl by the molar ratio of HCl to trichlorosilane. This approach is considered reasonable because qualitative and quantitative data on chlorosilanes suggest that the HCl hydrolysis product is largely responsible for the acute toxicity of the chlorosilanes.

Molar adjustment factor: 3

Data adequacy: Data were considered adequate for the derivation of AEGL-3 values for chlorosilanes based on analogy to HCl. Confidence in the AEGL-3 values for chlorosilanes is high, reflecting the availability of lethality data on 11 of the 26 chlorosilanes considered and evidence for the role of HCl as the proximate toxicant. No additional research is needed on AEGL-3 end points.

AEGL-3 VALUES FOR TETRACHLOROSILANE

Key reference: NRC (National Research Council). 2004. Hydrogen chloride. Pp. 77-122 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol. 4. Washington, DC: National Academies Press.

End point/Concentration/Rationale: AEGL-3 values for tetrachlorosilane were derived by adjusting the AEGL-3 values for HCl by the molar ratio of HCl to tetrachlorosilane. This approach is considered reasonable because qualitative and quantitative data on chlorosilanes suggest that the HCl hydrolysis product is largely responsible for the acute toxicity of the chlorosilanes.

Molar adjustment factor: 4

Data adequacy: Data were considered adequate for the derivation of AEGL-3 values for chlorosilanes based on analogy to HCl. Confidence in the AEGL-3 values for chlorosilanes is high, reflecting the availability of lethality data on 11 of the 26 chlorosilanes considered and evidence for the role of HCl as the proximate toxicant. No additional research is needed on AEGL-3 end points.

APPENDIX E

DERIVATION SUMMARY TABLES FOR HYDROGEN CHLORIDE (Excerpted from NRC 2004)

Derivation Summary

AEGL-1 VALUES FOR HYDROGEN CHLORIDE

AEGL-2 VALUES FOR HYDROGEN CHLORIDE

AEGL-2 VALUES FOR HYDROGEN CHLORIDE

AEGL-3 VALUES FOR HYDROGEN CHLORIDE

AEGL-3 VALUES FOR HYDROGEN CHLORIDE

APPENDIX F

CATEGORY PLOTS FOR SELECTED CHLOROSILANES

FIGURE F-1 Category plot for monochlorosilanes. *Data plotted are for trimethyl chlo-rosilane and dimethyl chlorosilane.

FIGURE F-2 Category plat of dichlorosilanes. *Data plotted are for methylvinyl dichlo-rosilane, dimethyl dichlorosilane, and methyl dichlorosilane.

FIGURE F-3 Category plot for trichlorosilanes. *Data plotted are for propyl trichlorosi-lane, vinyl trichlorosilane, methyl trichlorosilane, and ethyl trichlorosilane.

FIGURE F-4 Category plot for tetrachlorosilane.