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Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13 (2012)

Chapter: 7 Trimethoxysilane and Tetramethoxysilane

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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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7

Trimethoxysilane and Tetramethoxysilane1

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

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1This document was prepared by the AEGL Development Team composed of Dana Glass (Oak Ridge National Laboratory), Mark Follansbee and Julie Klotzbach (SRC, Inc.), Chemical Manager Robert Benson (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).

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

experience notable discomfort, irritation, or certain asymptomatic, nonsensory 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 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 concentrations 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

Trimethoxysilane and tetramethoxysilane are colorless liquids with ester-like odors. They are structural analogs and are in the organic silane family. Both chemicals have similar toxicologic effects in the lung and eye. Little relevant data on the toxicity of the chemicals in either humans or laboratory animals are available.

AEGL-1 values were not recommended for trimethoxysilane because of inadequate data. Data were also inadequate to derive AEGL-2 values, so values were derived by taking one-third of the AEGL-3 values. The Standing Operating Procedure for determining AEGL values (NRC 2001) specifies that AEGL-2 values can be derived by this method when a chemical has a steep dose-response curve. AEGL-3 values for trimethoxysilane were determined on the basis of mortality data from 1- and 4-h LC50 (lethal concentration, 50% lethality) inhalation studies in rats (Nachreiner and Dodd 1988). Points of departure were the calculated LC01 (lethal concentration, 1% lethality) values of 263 ppm for 10 min, 123 ppm for 30 min, 76.3 ppm for 1 h, 29.3 ppm for 4 h, and 18.2 ppm for 8 h. A total uncertainty factor of 30 was used. A factor of 3 was applied for interspecies differences, because similar effects were observed in rats, mice, and hamsters exposed at the same concentration in a 5-day inhalation study (Dow Corning Corp. 1981). The default value of 10 was used for intraspecies variabil-

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

ity, because no data were available to estimate human variability and it was not clear that trimethoxysilane acts as a simple chemical irritant in the lungs (NRC 2001). Time scaling was performed using the concentration-time relationship equation Cn × t = k, where C = concentration, t = time, k is a constant, and n generally ranges from 0.8 to 3.5 (ten Berge et al. 1986). An empirical value for n of 1.45 was calculated for trimethoxysilane. AEGL values for trimethoxysilane are presented in Table 7-1.

AEGL-1 values were not recommended for tetramethoxysilane because of inadequate data. AEGL-2 values for tetramethoxysilane were derived from an inhalation study in which rats were exposed to tetramethoxysilane at concentrations up to 45 ppm for 6 h/day, 5 days/week for 28 days (Kolesar et al. 1989). No deaths or effects on the respiratory or ocular epithelium were observed at 0, 5, and 10 ppm. At 15 ppm, nasal changes indicative of minimal acute inflammation were found in two of 20 rats and acute keratitis of cornea was observed in four of 20 rats, indicating a no-effect level for irreversible effects. At 30 and 45 ppm, lesions more severe than defined by AEGL-2 and deaths were observed, respectively. Therefore, 15 ppm was used as the point of departure for calculating AEGL-2 values. Extrapolation to different exposure durations was performed using the equation Cn × t = k (ten Berge et al. 1986), where n = 3 for extrapolation to 30 min, 1 h, and 4 h, and n = 1 for extrapolation to 8 h. The 30-min value was adopted as the 10-min value because extrapolating from durations of more than 4 h to 10 min is not recommended (NRC 2001). A total uncertainty factor of 30 was used. A factor of 3 was applied for interspecies differences because in a 5-day inhalation study with trimethoxysilane, a structural analog, effects were similar in rats, mice, and hamsters (Dow Corning Corp. 1981). A default value of 10 was used for the intraspecies variability because there were no data to estimate human variability and it was not clear that tetramethoxysilane acts as a simple chemical irritant in the lungs (NRC 2001).

AEGL-3 values for tetramethoxysilane were derived from a 4-h LC50 inhalation study in rats (Dow Corning Corp. 1992). The data were analyzed with EPA’s Benchmark Dose Calculation Software, version 1.3.2 (EPA 2005), and values were calculated using log-probit analysis. A BMCL05 (benchmark concentration, 95% lower confidence limit with 5% response) of 26 ppm was used as the basis for determining AEGL-3 values. For completeness, a BMC01 (benchmark concentration with 1% response) of 30 ppm was also derived, but the lower BMCL05 value was used. Extrapolation to different exposure durations was performed using the equation Cn × t = k (ten Berge et al. 1986), where n = 3 for extrapolation to 30 min and 1 h and n = 1 for extrapolation to 8 h. The 30-min value was adopted as the 10-min value because extrapolating from 4 h to 10 min is not recommended (NRC 2001). A total uncertainty factor of 30 was used. An uncertainty factor of 3 was used for interspecies differences because in a 5-day inhalation study with trimethoxysilane, a structural analog of tetramethoxysilane, effects were similar in rats, mice, and hamsters (Dow Corning Corp. 1981). A default value of 10 was used for intraspecies variability because there were no data to estimate human variability and it was not clear that tetramethox-

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

ysilane acts as a simple chemical irritant in the lungs (NRC 2001). The AEGL values for tetramethoxysilane are presented in 7-2.

1. INTRODUCTION

Trimethoxysilane and tetramethoxysilane are organosilanes (silicon esters). Silicon esters are silicon compounds that contain an oxygen bridge from silicon to an organic group (Si-OR). These compounds are classified according to whether the Si-OR bond is expected to remain intact or hydrolyzed in the final application. Trimethoxysilane and tetramethoxysilane are both alkoxysilanes and generally have sweet-fruity odors that become less apparent as the molecular weight increases. Both chemicals can be absorbed into the corneal tissue and cause eye damage (Arkles 2000). Tetramethoxysilane is used in the ceramic industry for closing pores, for coating metal surfaces, and as a bonding agent in paints and lacquers. Trimethoxysilane is used as an intermediate for producing silane. Whereas inorganic silanes are oxidized spontaneously on contact with oxygen and air, the organosilanes are more stable.

TABLE 7-1 Summary of AEGL Values for Trimethoxysilane

Classification 10 min 30 min 1 h 4 h 8 h End Point (Reference)
AEGL-1 (nondisabling) NR NR NR NR NR
AEGL-2 (disabling) 2.9 ppm (15 mg/m3) 1.4 ppm (7.0 mg/m3) 0.83 ppm (4.2 mg/m3) 0.33 ppm (1.7 mg/m3) 0.20 ppm (1.0 mg/m3) One-third of AEGL-3 values
AEGL-3 (lethality) 8.8 ppm (44 mg/m3) 4.1 ppm (21 mg/m3) 2.5 ppm (13 mg/m3) 0.98 ppm (5.0 mg/m3) 0.61 ppm (3.1 mg/m3) LC01 values (Nachreiner and Dodd 1988)

Abbreviations: LC01, lethal concentration, 1% lethality; NR, not recommended.

TABLE 7-2 Summary of AEGL Values for Tetramethoxysilane

Classification 10 min 30 min 1 h 4 h 8 h End Point (Reference)
AEGL-1 (nondisabling) NR NR NR NR NR
AEGL-2 (disabling) 1.1 ppm (6.8 mg/m3) 1.1 ppm (6.8 mg/m3) 0.91 ppm (5.6 mg/m3) 0.57 ppm (3.5 mg/m3) 0.38 ppm (2.4 mg/m3) No-effect level for irreversible effects (Kolesar et al. 1989)
AEGL-3 (lethality) 1.7 ppm (11 mg/m3) 1.7 ppm (11 mg/m3) 1.4 ppm (8.7 mg/m3) 0.87 ppm (5.4 mg/m3) 0.43 ppm (2.7 mg/m3) Threshold for lethality (Dow Corning Corp. 1992)

Abbreviations: NR, not recommended

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

Selected chemical and physical properties for trimethoxysilane and tetramethoxysilane are presented in Table 7-3.

2. HUMAN TOXICITY DATA

2.1. Acute Lethality

No data were available on the acute lethality of trimethoxysilane or tetramethoxysilane in humans.

2.2. Nonlethal Toxicity

No data were available on the toxicity of trimethoxysilane or tetramethoxysilane in humans.

TABLE 7-3 Physical and Chemical Properties of Trimethoxysilane and Tetramethoxysilane

Parameter Trimethoxysilane (AIHA 1997) Tetramethoxysilane (AIHA 1998)
Synonyms TMS Methyl silicate; tetramethoxyorthosilicate; TMOS
CAS registry no. 2487-90-3 681-84-5
Chemical formula C3H10O3Si C4 H12 O4Si
Molecular weight 122.22 152.22
Physical state Colorless liquid Clear, colorless liquid
Odor Ester odor Faint, ester-like
Melting point -114°C 5°C
Boiling point 84°C 122°C
Flash point 7.2°C (closed cup) 20°C (closed cup)
Density (air = 1) 4.2 5.3
Solubility (in water) Reacts slowly; reacts with water liberating methanol Reacts, generating methanol
Vapor pressure 57 mm Hg at 20°C 10.1 mm Hg at 20°C
Specific gravity 0.95 at 20°C 1.03 g/cc at 20°C
Explosive limits (volume % in air) Lower limit: 4.3% at 34°C
Upper limit: 40.1% at 62°C
No data available
Conversion factors 1 ppm = 5.0 mg/m3
1 mg/m3 = 0.2 ppm
1 ppm = 6.2 mg/m3
1 mg/m3 = 0.16 ppm
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

2.2.1. Odor Threshold

Inadequate data were available to calculate an odor threshold for trimethoxysilane or tetramethoxysilane.

2.2.2. Experimental Studies

No data were available on experimental studies in humans with trimethoxysilane or tetramethoxysilane.

2.2.3. Epidemiologic Studies/Occupational Exposures

Secondary sources indicate that both trimethoxysilane (AIHA 1997) and tetramethoxysilane (BIBRA 1988) cause ocular irritation; however, primary sources describing such effects were not available.

2.2.4. Clinical Studies

No data were available on clinical studies of trimethoxysilane or tetramethoxysilane.

2.3. Neurotoxicity

No data were available on the neurotoxicity of trimethoxysilane or tetramethoxysilane in humans.

2.4. Developmental and Reproductive Toxicity

No data were available on the developmental and reproductive toxicity of trimethoxysilane or tetramethoxysilane in humans.

2.5. Genotoxicity

No data were available on the genotoxicity of trimethoxysilane or tetramethoxysilane in humans.

2.6. Carcinogenicity

No data were available on the chronic toxicity or carcinogenicity of trimethoxysilane or tetramethoxysilane in humans.

2.7. Summary

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

Very little data were available on human exposure to trimethoxysilane or tetramethoxysilane.

3. ANIMAL TOXICITY DATA: TRIMETHOXYSILANE

3.1. Acute Lethality

An LC50 study was conducted using Good Laboratory Practices (GLP) by Union Carbide (Nachreiner and Dodd 1988). Five male and five female Sprague-Dawley rats were exposed to trimethoxysilane at concentrations of 19, 39, 71, or 166 ppm for 4 h or at 68, 155, 342, or 643 ppm for 1 h. Liquid trimethoxysilane was metered from a syringe pump into a heated evaporator and the resulting vapor was carried into the chamber by an inlet air stream. A gas chromatograph equipped with a flame-ionization detector was used to measure chamber concentrations of the trimethoxysilane. Because methanol can be produced from the breakdown of trimethoxysilane with moisture, methanol concentrations also were measured. The highest methanol vapor concentration was 173 ppm in the 1-h study and 66 ppm in the 4-h study. Methanol production was controlled by limiting the relative humidity of the chamber. The 4-h LC50 (with 95% confidence level) for trimethoxysilane was 81 ppm for males, 42 ppm for females, and 60 ppm for both sexes. The 1-h LC50 (with 95% confidence level) was 161 ppm for males, 146 ppm for females, and 154 ppm for both sexes. Those values were determined by a modified method of Finney (1964) using probit analysis. Mortalities were observed at all of the concentrations except 19 ppm in the 4-h group and 68 ppm in the 1-h group, with all deaths occurring during the 14-day post-exposure observation period. Mortality data are presented in Table 7-4.

Clinical signs were observed on the day of exposure in all groups, except for the 68-ppm (1 h) and 19-ppm (4 h) groups, and included: hyperactivity followed by hypoactivity; respiratory irritation; ocular irritation; and ataxia and slow righting reflex (71 ppm only). The following clinical signs were observed post exposure mostly beginning about day 5: unkempt fur, perinasal encrustation, decreased respiratory rate, body weight loss, and audible respiration. These effects were observed in all groups except for the 68-ppm group (1 h), which only had unkempt hair the last week of the post exposure period and the rats in the 19-ppm group (4 h), which had no clinical signs. The primary gross lesion identified in the animals that died was a red discoloration of the lungs. Rats in the 643-ppm group (1 h) or 166-ppm group (4 h) also had dark purple discoloration of the liver and fluid in the trachea. No gross lesions were observed in the animals that died in the 39- or 71-ppm groups. Microscopic examination of the lungs showed lesions that increased in severity and incidence with increasing

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

TABLE 7-4 Summary of Mortality in Rats Exposed to Trimethoxysilane by Inhalation

Concentration (ppm) Sex Mortality Day of death (post exposure)
1-h exposure
68 Male 0/5 Not applicable
Female 0/5 Not applicable
155 Male 2/5 Days 5 and 9
Female 3/5 Two deaths on day 7, one on day 8
342 Male 5/5 One on day 7, and twp on days 8 and 9
Female 5/5 One on day 6, 7, and 9; two on day 10
643 Male 5/5 1 on days 1, 2, and 9 and 2 on day 8
Females 5/5 1 on days 7, 9, and 13 and 2 on day 8
4-h exposure
19 Male 0/5 Not applicable
Female 0/5 Not applicable
39 Male 0/5 0/5
Female 1/5 One on day 14
71 Male 2/5 One on days 13 and 14
Female 5/5 One on days 6, 7, 9; two on day 13
166 Male 5/5 One on days 5, 7, and 10; two on day 6
Female 5/5 One on days 6, 8, and 10; two on day 7

Source: Nachreiner and Dodd 1988.

concentration and exposure duration; however, statistical analysis was not performed. The study author and the pathologist for the study both concluded that pulmonary lesions increased in severity with increasing concentration and exposure duration with animal death caused by lung dysfunction.

Pathologic findings in the lungs of the rats exposed to trimethoxysilane for 1 h included:

• 643 ppm: four males and four females; marked to severe necrotic bronchiolitis in all lungs, squamous metaplasia of bronchiolar epithelium in three lungs, and marked to severe vascular changes (congestion, edema) in all lungs.

• 342 ppm: one male and three females; vascular changes in all lungs, and some degree of bronchial epithelial changes and submucosal fibrosis in all lungs.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

• 155 ppm: four males and three females; necrotic bronchiolitis in some lungs, severe atelectasis in one lung, and most vascular and inflammatory lesions were of at least moderate severity.

• 68 ppm: three males and three females; all survived; mild to moderate vascular and inflammatory changes, and considerable variation in severity of lung reaction.

Pathologic findings in the lungs of rats exposed to trimethoxysilane for 4 h included:

• 166 ppm: three males and four females; marked to severe necrotic bronchiolitis in all lungs, and moderate to marked vascular/inflammatory changes in all lungs.

• 71 ppm: one male; necrotic bronchiolitis, congestion, and edema.

• 39 ppm: three males and three females; all rats survived until day 14; necrotic bronchiolitis in four lungs, atelectasis in two lungs, and considerable variability in vascular/inflammatory lesions.

• 19 ppm: three males and three females; all survived; two females had mild inflammatory cells; two males had moderate bronchiolar epithelial cell degeneration.

In this same study, Nachreiner and Dodd (1988) conducted static exposures. Five rats per sex were exposed for 10 or 60 min to a near saturated vapor atmosphere of trimethoxysilane. In the 1-h static exposure, the chamber concentration of trimethoxysilane decreased from 60,000 ppm to 3,000 ppm within the first 22 min while the methanol concentration increased to 111,000 ppm. During the 10-min static exposure, the concentration of trimethoxysilane decreased from 56,000 ppm to 47,000 ppm, and methanol increased to 69,000 ppm. All animals died during or within 2 h post exposure. Clinical signs in these animals included tremors and respiratory difficulty; gross examination showed red discoloration of the lungs and fluid in the trachea.

3.2. Acute Nonlethal

Ocular and dermal irritation studies of trimethoxysilane were conducted in rabbits (Union Carbide 1988). A 4-h application of 0.5 mL of trimethoxysilane to occluded rabbit skin caused moderate to severe erythema, severe edema, and necrosis in all six rabbits tested. Edema was gone by day 14 and erythema by day 7; however, the chemical was given an overall rating of severe irritant because ulceration, scabs, and alopecia remained through day 14. Two of the rabbits were found dead at day 12 but it was unclear if their deaths were related to treatment.

Trimethoxysilane (0.1 mL) placed in the eyes of six rabbits resulted in corneal opacity in three rabbits and iritis and moderate to severe conjunctival

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

irritation in all rabbits. All lesions resolved by day 7. After 0.01 mL of trimethoxysilane was placed in the eye, five of six rabbits had minor to moderate corneal opacity, and all rabbits had iritis and moderate to severe conjunctival irritation. No corneal lesions were reported when 0.005 mL was tested, but irisitis was observed in four of six rabbits.

3.3. Repeat Exposure Studies

3.3.1. Rats

In a study using GLP, 10 Sprague-Dawley rats per sex were exposed 7 h/day, 5 days/week for 4 weeks to trimethoxysilane at concentrations of 0.5, 5.0, or 10.0 ppm (Breckenridge et al. 1980). Animals were exposed whole body in four 400-L volume chambers. Air flow through the chambers was maintained at 45 L/min. Rats were not provided food or water during exposure. Chamber temperature, humidity, and concentration were measured continually during the exposure. The chamber concentrations were measured hourly by an infrared-gas analyzer. The concentrations were achieved after a 30-min equilibration period. Controls were exposed to filtered room air. During weeks 2 and 3 of treatment, 60% of the high-concentration animals died and 40% of the mid-concentration animals died by the end of the fourth week. No mortalities occurred in the control- or low-concentration groups. Exposure in the high-concentration group was terminated at day 21 and the survivors immediately sacrificed due to the high mortality rate. High- and mid-concentration animals exhibited lung congestion, generalized weakness, and a statistically significant decrease in body weight and food consumption. The low-concentration group was comparable to controls and showed no clinical signs. Histopathologic examination was performed on the control, low-concentration, and high-concentration animals only. All 20 rats in the 10-ppm group had bronchitis and bronchiolitis, whereas none of the rats in the 0.5-ppm and control groups exhibited these effects. Hematology results showed a concentration-dependent increase in red blood cells, hemoglobin, and hematocrit in the mid- and high-concentration animals and a concentration-dependent decrease in the white blood cells in most of the treated animals.

In a study by Union Carbide (1991), Fisher 344 rats were exposed to trimethoxysilane vapor at 0 (control), 0.2 ± 0.05 (standard deviation), 0.9 ± 0.12 (1 ppm), or 4.9 ± 0.34 (5 ppm) for 6 h/day. The rats were exposed for a total of nine exposures over an 11-day period. Ten rats of each sex were tested in the 0.2- and 1-ppm groups, and 15 of each sex in the control- and 5-ppm group. The additional five animals in the latter two groups were to be kept for a postexposure recovery period; however, mortality was too high in the 5-ppm group (14/15 males and 12/15 females died between days 8 and 12) to allow for a postexposure observation period. Table 7-5 presents observations at each concentration.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

3.3.2. Rats, Mice, Hamsters, and Rabbits

In a repeat exposure study, Sprague-Dawley (BR) rats, (ICR) BR mice, LVG (SYR) hamsters, and New Zealand White rabbits were exposed to trimethoxysilane at concentrations of 0, 10, 25, or 50 ppm for 7 h/day for 5 consecutive days, with a 14-day observation period post exposure (Dow Corning Corp. 1981). Five animals per sex were used in the studies with rats, mice, and hamsters, and two animals per sex were used in the study with rabbits. Table 7-6 presents the mortality data for this study. The investigators calculated 5-day LC50 values of 13, 14, 72, and 1 ppm for the rats, mice, hamsters, and rabbits, respectively. The report stated that the rabbits could have had a preexisting viral condition that was exacerbated under study conditions, thus resulting in high mortality. The laboratory had experienced this scenario in other studies with rabbits from the same supplier.

All animals had similar clinical signs of gasping, depression, and nasal discharge (see Table 7-7). In the animals that died, lung congestion, atelectosis, and hemorrhage were observed; however, raw data were not provided. The study author reported that the animals killed at the end of the observation period had the same effects, but they were less severe.

TABLE 7-5 Observations in the Union Carbide (1991) Study of Rats Exposed to Trimethoxysilane

0 0.2 ppm 1 ppm 5 ppm
No clinical signs Laryngitis in 1/10 males, 2/10 females Weight loss; increased lung weight; bronchopneumonia (10/10 males; 10/10 females); lymphoid tissue depletion (lymph nodes) 87% mortality; severe irritation (labored breathing, gasping); weight loss; decreased organ weight (spleen, liver, kidney); increased erythrocytes, hemoglobin,, and hematocrit; lymphocytopenia; lymphoid depletion; bronchopneumonia (1/1 male and 2/3 female survivors; 11/14 males and 12/12 females that died)

TABLE 7-6 Mortality Results in Dow Corning Corp. (1981) Study of Trimethoxysilane

Concentration (ppm) Rats Mice Hamsters Rabbits
0 0/10 0/10 0/10 0/2
10 3/10 5/10 0/10 2/2
25 9/10 4/10 3/10 2/2
50 10/10 10/10 3/10 2/2
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

TABLE 7-7 Clinical Signs in Dow Corning Corp. (1981) Study of Trimethoxysilane

Concentration (ppm) Rats Mice Hamsters Rabbits
0 None None None None
10 Depression + Nasal discharge + Depression + Nasal discharge + Depression + Nasal discharge + Depression + Nasal discharge ++
25 Depression + Nasal discharge + Gasping NS Depression + Nasal discharge + Gasping + Depression ++ Nasal discharge + Gasping + Depression ++ Nasal discharge ++ Gasping ++
50 Depression + Nasal discharge + Gasping + Depression + Nasal discharge + Gasping + Depression ++ Nasal discharge + Gasping + Depression ++ Nasal discharge +++ Gasping +++

3.4. Neurotoxicity

No data were available on neurotoxicity of trimethoxysilane.

3.5. Developmental and Reproductive Toxicity

No data were available on the developmental and reproductive toxicity of trimethoxysilane.

3.6. Genotoxicity

Trimethoxysilane was tested for mutagenicity in Salmonella typhimurium (TA1535, TA1537, TA98, and TA100) and Escherichia coli (wP2) in a reverse mutation assay with and without metabolic activation (Isquith et al. 1987). Positive controls were used. No evidence of mutagenic potential was observed in any assay, and positive controls produced appropriate responses.

3.7. Chronic Toxicity and Carcinogenicity

No chronic toxicity or carcinogenicity studies on trimethoxysilane were available.

3.8. Summary

The data on trimethoxysilane were limited. Rats exposed to trimethoxysilane had 1- and 4-h LC50s of 154 ppm and 60 ppm, respectively (Nachreiner and Dodd 1988). Mortality was observed at concentration of 155 ppm and greater in the 1-h study and at 39 ppm and greater in the 4-h study. Ocular and dermal irri-

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

tation were present in rabbits when trimethoxysilane was placed in the eyes or occluded on the skin for 4 h (Union Carbide 1988). Repeat exposure studies resulted in mortality at concentrations of 5 ppm or greater in rats after nine exposures over 11 days (Union Carbide 1991) or when exposed for up to 4 weeks (Breckenridge et al. 1980). In another repeat exposure study, hamsters, mice, and rats had similar clinical signs following exposure to trimethoxysilane for 5 days and mortality occurred at 10 ppm or greater in the mice and rats (Dow Corning Corp. 1981). Trimethoxysilane demonstrated no mutagenic potential in a reverse bacterial mutation assay with or without metabolic activation (Isquith et al. 1987).

4. ANIMAL TOXICITY DATA: TETRAMETHOXYSILANE

4.1. Acute Lethality

Groups of 10 male Sprague-Dawley rats were exposed nose-only to tetramethoxysilane at 31, 50, or 88 ppm for 4 h (Dow Corning Corp. 1992). Vapor was generated by bubbling clean dry air through the test material. Rats were exposed nose-only in a chamber designed to contain 10 rats in a radial pattern on two planes of five rats each. Concentration was monitored continuously by long-path gas infrared spectroscopy. Animals were observed for abnormalities several times during the study and during the 2-week recovery period. Body weight was also recorded.

Mortality occurred at 50 and 88 ppm. Nine rats in the 88-ppm group and three in the 50-ppm group died within 7 days post exposure. An LC50 of 63 ppm (95% confidence limits 51-78 ppm) was determined by probit analysis. Gasping and coughing were observed in all animals of the 50- and 88-ppm groups during the post-exposure observation period. However, these effects abated within 2 weeks. All of the animals in the 31-ppm group exhibited weight gain by the end of the recovery period. Rats in the 50-ppm group showed initial weight loss but those that survived gained weight by the end of the recovery period. The only survivor in the 88-ppm group also had weight gain after initial weight loss. Necropsy revealed dose-related lung damage that ranged from involvement of small areas of the lobe (five of 10 rats in the 31-ppm group and three of three rats in the 50-ppm group) to involvement of entire lung lobes (5/10 at 31-ppm group and 10/10 at 88-ppm group). Severity and microscopic lesions were not described. The report did not mention any use of control rats.

4.2. Acute Nonlethal

No acute studies were identified that showed nonlethal effects for tetramethoxysilane.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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4.3. Repeat Exposure Studies

4.3.1. Rats

Groups of 10 Sprague-Dawley rats per sex were exposed to tetramethoxysilane by inhalation for 6 h/day, 5 days/week for 28 days at vapor concentrations of 0, 1, 5, or 10 ppm (Phase 1) and 0, 15, 30, or 45 ppm (Phase 2) (Kolesar et al. 1989). Exposures were conducted in a 450-L chamber operated under dynamic conditions. Air flow was maintained at approximately 120 L/min, and tetramethoxysilane vapors were created using the glass J-tube method of Miller et al. (1980). Chamber concentration was measured once an hour with a gas chromatograph equipped with a flame-ionization detector. Clinical observations were made daily, body weight was measured twice a week, and food consumption was measured weekly. Blood for hematology and clinical chemistry was collected at the study’s termination; however, data were not collected on rats in the 45-ppm group.

All animals exposed at 45 ppm either died or were killed during the 28-day study. No effects were observed in any rats exposed at 0, 1, 5, or 10 ppm. A statistically significant difference was observed in food consumption, body weight, and clinical parameters in rats exposed at 30 ppm. Males exposed at 15 ppm had only a decrease in total protein. No microscopic lesions were found in the respiratory tract or eyes of rats exposed at 1, 5, or 10 ppm. However, at 15 ppm or greater, tetramethoxysilane-related ocular and respiratory tract changes were observed. Changes were most severe in the upper respiratory tract. The lesions included ulceration, desquamation, and inflammation of the respiratory epithelium, with a large amount of exudate in the nasal cavity. Ocular lesions were observed at 15, 30, and 45 ppm. At 30 and 45 ppm, ocular lesions included desquamation of the central corneal epithelium. While effects appeared to be more severe in the 30-ppm group than the 45-ppm group, this was likely a result of the longer duration of exposure experienced by the 30-ppm group due to the high mortality in the 45-ppm group. At 15 ppm, four of 20 rats had minimal acute keratitis with no epithelial desquamation. These lesions were severe at 45 ppm, moderate to severe at 30 ppm, minimal at 15 ppm, and not seen at 10 ppm.

4.4. Neurotoxicity

No data were available on neurotoxicity of tetramethoxysilane in laboratory animals.

4.5. Developmental and Reproductive Toxicity

No data were available on developmental and reproductive toxicity of tetramethoxysilane in laboratory animals.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

4.6. Genotoxicity

No data were available on genotoxicity of tetramethoxysilane in laboratory animals.

4.7. Chronic Toxicity and Carcinogenicity

No data were available on chronic toxicity or carcinogenicity of tetramethoxysilane in laboratory animals.

4.8. Summary

There were few animal studies of tetramethoxysilane. Lethality was reported in a study of rats exposed nose-only to tetramethoxysilane at 50 ppm. The only other study was a repeat exposure study in which rats were exposed to tetramethoxysilane at concentrations up to 45 ppm for 28 days. No effects were noted at 10 ppm or less, and minimal effects were observed at 15 ppm indicating a steep dose-response curve.

5. SPECIAL CONSIDERATIONS

5.1. Metabolism and Disposition

No metabolism or disposition studies were available for trimethoxysilane or tetramethoxysilane.

5.2. Mechanism of Toxicity

The exact mechanism of toxicity is not known for trimethoxysilane or tetramethoxysilane. Epithelial tissue is the target tissue for these chemicals, especially in the eye and respiratory tract. Both chemicals appear to have the same toxicologic effects and have similar LC50 values in rats.

5.3. Structure-Activity Relationships

Trimethoxysilane and tetramethoxysilane are both organic silanes and are classified as silane esters. They are both used as intermediates in the production of silicone and are structural analogs.

5.4. Other Relevant Information

No additional relevant information was available.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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5.4.1. Species Variability

Trimethoxysilane was tested in an inhalation study comparing effects on hamster, rats, mice, and rabbits (Dow Corning Corp. 1981). Rats, mice, and hamsters had similar clinical effects. LC50 values in rats and mice exposed to trimethoxysilane for 5 days were also similar; however, the results are questionable because of the validity of having LC50 values in a 5-day study. Rabbits exhibited high mortality but it appeared to be from a secondary infection within the population. Little species variability also is expected for tetramethoxysilane because the two chemicals are structural analogs and have similar rat 4-h LC50 values (60 ppm for trimethoxysilane and 63 ppm for tetramethoxysilane).

5.4.2. Susceptible Populations

Little human data are available on trimethoxysilane or tetramethoxysilane. Secondary sources indicate that the chemicals are strong ocular irritants in humans, and animal data supports those reports. Animal data also show that both chemicals can cause lung damage; therefore, anyone with compromised lung function would be considered more at risk from exposure to trimethoxysilane or tetramethoxysilane.

5.4.3. Concentration-Exposure Duration Relationship

The concentration-exposure duration relationship for many irritant and systemically-acting vapors and gases can be described by the relationship Cn × t = k, where the exponent, n, ranges from 0.8 to 3.5 (ten Berge et al. 1986). For trimethoxysilane, the value of n was 1.45. That value was derived using the ten Berge formula and the rat mortality data from the acute rat inhalation studies by Nachreiner and Dodd (1988).

The available data on tetramethoxysilane were inadequate to derive an empirical value for n. In the absence of chemical specific data, the default values of n = 3 was applied to extrapolate to shorter durations and n = 1 was applied to extrapolate to longer durations, to provide AEGL values that are protective of human health (NRC 2001).

6. DATA ANALYSIS FOR AEGL-1

6.1. Summary of Human Data Relevant to AEGL-1

No human data were available to determine AEGL-1 values for either trimethoxysilane or tetramethoxysilane.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

6.2. Summary of Animal Data Relevant to AEGL-1

Insufficient animal data were available for determining AEGL-1 values for either trimethoxysilane or tetramethoxysilane.

6.3. Derivation of AEGL-1 Values

AEGL-1 values were not derived for trimethoxysilane or tetramethoxysilane because of insufficient data. Although consideration was given to using data from repeat exposure studies to determine AEGL-1 values, both chemicals lack good warning properties based on odor and the values derived would be very low for trimethoxysilane and very similar to AEGL-2 values for tetramethoxysilane.

7. DATA ANALYSIS FOR AEGL-2

7.1. Summary of Human Data Relevant to AEGL-2

No human data were available to determine AEGL-2 values for trimethoxysilane or tetramethoxysilane.

7.2. Summary of Animal Data Relevant to AEGL-2

Only one acute inhalation study on trimethoxysilane was found (Nachreiner and Dodd 1988). Thus, the available data were inadequate for determining AEGL-2 values for trimethoxysilane.

For tetramethoxysilane, the data most relevant to AEGL-2 values was a repeat exposure study in rats (Kolesar et al. 1989). Rats were exposed to tetramethoxysilane at 0, 1, 5, 10, 15, 30, or 45 ppm for 6 h/day, 5 days/week for 28 days. Deaths occurred at 45 ppm. At 30 ppm, nasal cavity ulceration was found in 18 of 20 animals, metaplasia of the lungs in 15 of 20 animals, and bilateral desquamation of the central corneal epithelium. These effects were more severe than the definition of AEGL-2. At 15 ppm, lung lesions, acute inflammation of the nasal epithelium, and acute keratitis were minimal.

7.3. Derivation of AEGL-2 Values

In the absence of sufficient animal data, AEGL-2 values for trimethoxysilane were obtained by taking one-third of the AEGL-3 values. This approach was used in accordance with the Standing Operating Procedures for determining AEGL values (NRC 2001) for chemicals with a steep dose-response curve when data are inadequate for calculating AEGL-2 values.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

AEGL-2 values for tetramethoxysilane were based on data from a repeat exposure study in rats (Kolesar et al. 1989). In that study, 15 ppm was the no-effect level for irreversible effects. Time scaling to different exposure durations was performed using the equation Cn × t = k (ten Berge et al. 1986), where n = 3 for extrapolation to 30 min, 1 h, and 4 h and n = 1 for extrapolation to 8 h. The 30-min value was adopted as the 10-min value because extrapolating from an exposure of 4 h or more to 10-min exposure is not recommended (NRC 2001). A total uncertainty factor of 30 was applied. A factor of 3 was used for interspecies differences rather than 10 because: (1) there are no human data to compare with the animal data; (2) comparative studies of trimethoxysilane (a structural and toxicologic analog of tetramethoxysilane) found similar effects over the same exposure concentration range (10-50 ppm) in rats, mice, and hamsters, suggesting that variability in response did not exceed a factor of 3; (3) the effects observed in animals included ocular irritation and lesions which have been observed in humans, suggesting a similar mode of action across species; and (4) the point of departure was based on a repeated-exposure study. A default value of 10 (NRC 2001) was used for intraspecies variability because there were no data to estimate human variability and it was not clear that tetramethoxysilane acts as a simple chemical irritant in the lungs. AEGL-2 values for trimethoxysilane and tetramethoxysilane are presented in Table 7-8.

8. DATA ANALYSIS FOR AEGL-3

8.1. Summary of Human Data Relevant to AEGL-3

No human data were available to determine AEGL-3 values.

8.2. Summary of Animal Data Relevant to AEGL-3

Rat inhalation studies were used to derive AEGL-3 values for both trimethoxysilane and tetramethoxysilane. For trimethoxysilane, LC50 data were available from an inhalation study of rats exposed to trimethoxysilane at concentrations of 19, 39, 71, or 166 ppm for 4 h or at 68, 155, 342, or 643 ppm for 1 h (Nachreiner and Dodd 1988). For tetramethoxysilane, LC50 data were available from a study in rats exposed nose-only to tetramethoxysilane at concentrations of 31, 50 or 88 ppm for 4 h (Dow Corning Corp. 1992).

8.3. Derivation of AEGL-3 Values

8.3.1. AEGL-3 Values for Trimethoxysilane

AEGL-3 values for trimethoxysilane were derived from the 1-h and 4-h LC50 data from the study by Nachreiner and Dodd (1988). Time scaling to dif-

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

ferent exposure durations was performed using the equation Cn × t = k (ten Berge et al. 1986). Mortality data for male and female rats were combined and the ten Berge formula was used to calculate an n value of 1.45 (ten Berge et al. 1986). Points of departure were the calculated LC01 values (lethal concentration, 1% lethality) of 263 ppm for 10 min, 123 ppm for 30 min, 76.3 ppm for 1 h, 29.3 ppm for 4 h, and 18.2 ppm for 8 h. A total uncertainty factor of 30 was used. A factor of 3 was used for interspecies differences because similar effects were observed in rats, mice, and hamsters exposed at the same concentrations in a 5-day inhalation study (Dow Corning Corp. 1981). A default value of 10 was used for intraspecies variability because there were no data to estimate human variability and was not clear that trimethoxysilane is acts as a simple chemical irritant in the lungs (NRC 2001). AEGL-3 values for trimethoxysilane are presented in Table 7-9.

8.3.2. AEGL-3 Values for Tetramethoxysilane

AEGL-3 values for tetramethoxysilane were derived from a study in rats exposed nose-only to tetramethoxysilane concentrations of 31, 50 or 88 ppm for 4 h (Dow Corning Corp. 1992). The calculated LC50 was 63 ppm. The data were analyzed using the EPA Benchmark Dose Calculation Software (EPA 2005) to determine a BMCL05 of 26 ppm. A BMC01 of 30 ppm also was calculated, but was not used because it was greater than the BMCL05. Values were scaled using the equation Cn × t = k where n ranges from 0.8 to 3.5 (ten Berge et al. 1986). The default values of n = 3 for extrapolation to 30 min and 1 h and n = 1 for

TABLE 7-8 AEGL-2 Values for Trimethoxysilane and Tetramethoxysilane

10 min 30 min 1 h 4 h 8 h
Trimethoxysilane
2.9 ppm (15 mg/m3) 1.4 ppm (7.0 mg/m3) 0.83 ppm (4.2 mg/m3) 0.33 ppm (1.7 mg/m3) 0.20 ppm (1.0 mg/m3)
Tetramethoxysilane
1.1 ppm (6.8 mg/m3) 1.1 ppm (6.8 mg/m3) 0.91 ppm (5.6 mg/m3) 0.57 ppm (3.5 mg/m3) 0.38 ppm (2.4 mg/m3)

TABLE 7-9 AEGL-3 Values for Trimethoxysilane and Tetramethoxysilane

10 min 30 min 1 h 4 h 8 h
Trimethoxysilane
8.8 ppm (44 mg/m3) 4.1 ppm (21 mg/m3) 2.5 ppm (13 mg/m3) 0.98 ppm (5.0 mg/m3) 0.61 ppm (3.1 mg/m3)
Tetramethoxysilane
1.7 ppm (11 mg/m3) 1.7 ppm (11 mg/m3) 1.4 ppm (8.7 mg/m3) 0.87 ppm (5.7 mg/m3) 0.43 ppm (2.7 mg/m3)
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

extrapolation to 8 h were used because of insufficient data to calculate an empirical value. The 30-min value was adopted as the 10-min value because extrapolating from 4 h to 10 min is not recommended (NRC 2001). A total uncertainty factor of 30 was used. A factor 3 was used for interspecies differences because: (1) there are no human data to compare with the animal data; (2) comparative studies of trimethoxysilane (a structural and toxicologic analog of tetramethoxysilane) found similar effects over the same exposure concentration range (10-50 ppm) in rats, mice, and hamsters, suggesting that variability in response did not exceed a factor of 3; (3) the effects observed in animals included ocular irritation and lesions which have been observed in humans, suggesting a similar mode of action across species; and (4) the point of departure was based on a repeated exposure study. A default value of 10 was used for intraspecies variability because there were no data to estimate human variability and it was not clear that tetramethoxysilane acts as a simple chemical irritant in the lungs (NRC 2001). AEGL-3 values for tetramethoxysilane are presented in Table 7-9.

9. SUMMARY OF AEGLS

9.1. AEGL Values and Toxicity End Points

AEGL values for trimethoxysilane and tetramethoxysilane are provided in Table 7-10. Data on both chemicals were insufficient for deriving AEGL-1 values. The data on trimethoxysilane were also insufficient for deriving AEGL-2, so values were calculated by taking one-third of the AEGL-3 values. AEGL-3 values for trimethoxysilane were derived from LC01 values calculated from a rat inhalation study (Nachreiner and Dodd 1988).

AEGL-2 values for tetramethoxysilane were derived from a repeat exposure study (Kolesar et al. 1989), in which 15 ppm was the no-effect level for irreversible effects. AEGL-3 values for tetramethoxysilane were derived from estimates of a BMCL05 on the basis of 4-h LC50 data (Dow Corning Corp. 1992).

9.2. Comparisons with Other Standards and Guidelines

Few standards have been established for either trimethoxysilane or tetramethoxysilane (see Tables 7-11 and 7-12). Emergency Response Planning Guidelines established by the American Industrial Hygiene Association (AIHA) are available for both chemicals (AIHA 2005), but documentation from all the sources used to develop those guidelines could not be obtained to understand the basis for those values. Trimethoxysilane has a Workplace Environmental Exposure Level (WEEL) of 0.05 ppm (AIHA 2005). That value was developed using animal data from longer term studies. The no-observed-effect level was reported to be 0.2 ppm in a 9-day exposure study in rats (Union Carbide 1991), and it was noted that 0.5 ppm resulted in decreased food consumption and weight gain in a 4-week study (Breckenridge et al.. 1980). AIHA concluded a WEEL of 0.05 ppm would be adopted as an 8-h time-weighted average (TWA).

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

TABLE 7-10 AEGL Values for Trimethoxysilane and Tetramethoxysilane

Classification 10 min 30 min 1 h 4 h 8 h
Trimethoxysilane
AEGL-1 (nondisabling) NR NR NR NR NR
AEGL-2 (disabling) 2.9 ppm (15 mg/m3) 1.4 ppm (7.0 mg/m3) 0.83 ppm (4.2 mg/m3) 0.33 ppm (1.7 mg/m3) 0.20 ppm (1.0 mg/m3)
AEGL-3 (lethality) 8.8 ppm (44 mg/m3) 4.1 ppm (21 mg/m3) 2.5 ppm (13 mg/m3) 0.98 ppm (5.0 mg/m3) 0.61 ppm (3.1 mg/m3)
Tetramethoxysilane
AEGL-1 (nondisabling) NR NR NR NR NR
AEGL-2 (disabling) 1.1 ppm (6.8 mg/m3) 1.1 ppm (6.8 mg/m3) 0.91 ppm (5.6 mg/m3) 0.57 ppm (3.5 mg/m3) 0.38 ppm (2.4 mg/m3)
AEGL-3 (lethality) 1.7 ppm (11 mg/m3) 1.7 ppm (11 mg/m3) 1.4 ppm (8.7 mg/m3) 0.87 ppm (5.4 mg/m3) 0.43 ppm (2.7 mg/m3)

Abbreviations: NR, not recommended

TABLE 7-11 Extant Standards and Guidelines for Trimethoxysilane

Guideline Exposure Duration
10 min 30 min 1 h 4 h 8 h
AEGL-1 NR NR NR NR NR
AEGL-2 2.9 ppm (15 mg/m3) 1.4 ppm (7.0 mg/m3) 0.83 ppm (4.2 mg/m3) 0.33 ppm (1.7 mg/m3) 0.20 ppm (1.0 mg/m3)
AEGL-3 8.8 ppm (44 mg/m3) 4.1 ppm (21 mg/m3) 2.5 ppm (13 mg/m3) 0.98 ppm (5.0 mg/m3) 0.61 ppm (3.1 mg/m3)
ERPG-1 (AIHA)a 0.5 ppm (2.5 mg/m3)
ERPG-2 (AIHA) 2.0 ppm (10 mg/m3)
ERPG-3 (AIHA) 5.0 ppm (25 mg/m3)
WEEL (AIHA)b 0.05 ppm (0.25 mg/m3)

aERPG (emergency response planning guidelines, American Industrial Hygiene Association [AHIA 2005]).
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 other than mild, transient adverse health effects or without perceiving a clearly defined objectionable odor.
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.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

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.
bWEEL (workplace environmental exposure level, American Industrial Hygiene Association [AIHA 2005] is the 8-h time-weighted average concentration allowed in a normal 8-h workday.

TABLE 7-12 Extant Standards and Guidelines for Tetramethoxysilane

Guideline Exposure Duration
10 min 30 min 1 h 4 h 8 h
AEGL-1 NR NR NR NR NR
AEGL-2 1.1 ppm (6.8 mg/m3) 1.1 ppm (6.8 mg/m3) 0.91 ppm (5.6 mg/m3) 0.57 ppm (3.5 mg/m3) 0.38 ppm (2.4 mg/m3)
AEGL-3 1.7 ppm (11 mg/m3) 1.7 ppm (11 mg/m3) 1.4 ppm (8.7 mg/m3) 0.87 ppm (5.4 mg/m3) 0.43 ppm (2.7 mg/m3)
ERPG-1 (AHIA)a N/A
ERPG-2 (AHIA) 10 ppm (63 mg/m3)
ERPG-3 (AHIA) 20 ppm (125 mg/m3)
TLV-TWA (ACGIH)b 1 ppm (6 mg/m3)
REL-TWA (NIOSH)c 1 ppm (6 mg/m3)
MAC (The Netherlands)d 1 ppm (6 mg/m3)

aERPG (Emergency Response Planning Guidelines, American Industrial Hygiene Association [AHIA 2005]).
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 other than mild, transient adverse health effects or without perceiving a clearly defined objectionable odor.
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.
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.
bTLV-TWA (threshold limit value - time weighted average, American Conference of Governmental Industrial Hygienists [ACGIH 2005]) is the time-weighted average concentration for a normal 8-h workday and a 40-h workweek, to which nearly all workers may be repeatedly exposed, day after day, without adverse effect.
cREL-TWA (recommended exposure limit - time weighted average, National Institute for Occupational Safety and Health [NIOSH 2010]) is defined analogous to the ACGIH TLV-TWA.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

dMAC (maximaal aanvaarde concentratie [maximal accepted concentration], Ministry of Social Affairs and Employment, The Hague, The Netherlands [MSZW 2004]) is defined analogous to the ACGIH TLV-TWA.

For tetramethoxysilane, 1 ppm was established by the National Institute for Occupational Safety and Health (NIOSH) as the recommended exposure limit (REL-TWA) (NIOSH 2010), by the American Conference of Governmental Industrial Hygienists (ACGIH) as the threshold limit value (TLV-TWA) (ACGIH 2005), and as the Dutch maximum acceptable concentration (MAC) (MSZW 2004). The ACGIH TLV-TWA was recommended in 1981 and was based on an undated, unpublished report (Frant et al.) available in the Netherlands and the accepted value is currently under review by the ACGIH TLV committee. NIOSH indicated that a concentration of 1 ppm would reduce risks of severe ocular effects. No information was obtained on how the Dutch MAC was derived.

9.3. Data Adequacy and Research Needs

Many data gaps were identified for both trimethoxysilane and tetramethoxysilane. Inadequate data exists for genotoxicity, reproductive and developmental toxicity, chronic toxicity, and carcinogenicity. Because of similar modes of action and similar LC 50 values, testing just one of the chemicals and applying the data to both could possibly reduce the number of animal studies required.

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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Isquith, A.J., R.T. Henrich, and J.M. Munten. 1987. Genetic Evaluation of Trimethyoxysilane in Bacterial Reverse Mutation Assays. Dow Corning Corp., Midland, MI. April 1987.

Kolesar, G.B., W.H. Siddiqui, R.G. Geil, R.M. Malczewski, and E.J. Hobbs. 1989. Subchronic inhalation toxicity of tetramethoxysilane in rats. Fundam. Appl. Toxicol. 13(2):285-295.

Miller, R.R., R.L. Letts, W.J. Potts, and M.J. McKenna. 1980. Improved methodology for generating controlled test atmospheres. Am. Ind. Hyg. Assoc. J. 41(11):844-846.

MSZW (Ministerie van Sociale Zaken en Werkgelegenheid). 2004. Nationale MAC-lijst 2004: Tetramethylorthosilicaat. Den Haag: SDU Uitgevers [online]. Available: http://www.lasrook.net/lasrookNL/maclijst2004.htm [accessed Sept. 28, 2012].

Nachreiner, D.J., and D.E. Dodd. 1988. Trimethoxysilane: Acute Vapor Inhalation Toxicity Study in Rats. Project Report No. 50-147. Union Carbide, Bushy Run Research Center, Export, PA.

NIOSH (National Institute for Occupational Safety and Health). 2010. NIOSH Pocket Guide to Chemical Hazards: Methyl silicate. 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/npgd0428.html [accessed Aug. 22, 2012].

NRC (National Research Council). 1993. Guidelines for Developing Community Emergency Exposure Levels for Hazardous Substances. Washington, DC: National Academy Press.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

NRC (National Research Council). 2001. Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals. Washington, DC: National Academy Press.

Rinehart, W.E., and T. Hatch. 1964. Concentration-time product (CT) as an expression of dose in sublethal exposures to phosgene. Ind. Hyg. J. 25(6):545-553.

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. Hazard. Mater. 13(3):301-309.

Union Carbide. 1988. Initial Submission: Trimethoxysilane: Acute Toxicity and Primary Irritancy Studies in Rats and Rabbits with Cover Letter Dated 051392 and Attachment. Union Carbide, Houston, TX. EPA Document No. 88-920002831. Microfiche No. OTS0539791.

Union Carbide. 1991. Letter from Union Carbide Chemical and Plastics Company to U.S. EPA Containing Preliminary Laboratory Findings from Immune System Toxicology Study with Attachments. Union Carbide, Houston, TX. EPA Document No. 89910000201. Microfiche No. OTS02048524.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

APPENDIX A

DERIVATION OF AEGL VALUES FOR TRIMETHOXYSILANE

Derivation of AEGL-1 Values

Inadequate data exist for deriving AEGL-1 values for trimethoxysilane.

Derivation of AEGL-2 Values

The available data were inadequate for deriving AEGL-2 values. Because of the steep dose response curve in the acute LC50 study (Nachreiner and Dodd 1988), AEGL-2 values were determined by reducing the AEGL-3 values by one-third (NRC 2001).

10-min AEGL-2: 8.8 ppm ÷ 3 = 2.9 ppm (15 mg/m3)
30-min AEGL-2: 4.1 ppm ÷ 3 = 1.4 ppm (7.0 mg/m3)
1-h AEGL-2: 2.5 ppm ÷ 3 = 0.83 ppm (4.2 mg/m3)
4-h AEGL-2: 0.98 ppm ÷ 3 = 0.33 ppm (1.7 mg/m3)
8-h AEGL-2: 0.61 ppm ÷ 3 = 0.20 ppm (1.0 mg/m3)

Derivation of AEGL-3 Values

Key study: Nachreiner, D.J., and D.E. Dodd. 1988. Trimethoxysilane: Acute Vapor Inhalation Toxicity Study in Rats. Project Report No. 50-147. Union Carbide, Bushy Run Research Center.
Toxicity end point: Calculated LC01 values from rat 1-h and 4-h data (sexes combined)
Time scaling: Cn × t = k (ten Berge et al. 1986)
n = 1.45 (0.99-1.91)
10 min 30 min 1 h 4 h 8 h
LC01 263 ppm 123 ppm 76.3 ppm 29.3 ppm 18.2 ppm
LC50 533 ppm 250 ppm 155 ppm 59.4 ppm 36.8 ppm
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×
Uncertainty factors: 3 for interspecies differences 10 for intraspecies variability
10-min AEGL-3: 263 ppm ÷ 30 = 8.8 ppm (44 mg/m3)
30-min AEGL-3: 123 ppm ÷ 30 = 4.1 ppm (21 mg/m3)
1-h AEGL-3: 76.3 ppm ÷ 30 = 2.5 ppm (13 mg/m3)
4-h AEGL-3: 29.3 ppm ÷ 30 = 0.98 ppm (5.0 mg/m3)
8-h AEGL-3: 18.2 ppm ÷ 30 = 0.61 ppm (3.1 mg/m3)
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

APPENDIX B

ACUTE EXPOSURE GUIDELINE LEVELS FOR TRIMETHOXYSILANE

Derivation Summary for Trimethoxysilane

AEGL-1 VALUES

Inadequate data exist for deriving AEGL-1 values for trimethoxysilane. Absence of AEGL-1 values does not indicate that exposure below AEGL-2 levels is safe.

AEGL-2 VALUES

10 min 30 min 1 h 4 h 8 h
2.9 ppm 1.4 ppm 0.83 ppm 0.33 ppm 0.20 ppm
Data adequacy: The available data were inadequate for deriving AEGL-2 values. Because of the steep dose response curve in the acute LC50 study (Nachreiner and Dodd 1988), AEGL-2 values were determined by reducing the AEGL-3 values by one-third (NRC 2001).

AEGL-3 VALUES

10 min 30 min 1 h 4 h 8 h
8.8 ppm 4.1 ppm 2.5 ppm 0.98 ppm 0.61 ppm
Key Reference: Nachreiner, D.J., and D.E. Dodd. 1988. Trimethoxysilane: Acute Vapor Inhalation Toxicity Study in Rats. Project Report No. 50-147. Union Carbide, Bushy Run Research Center, Export, PA.
Test Species/Strain/Number: Rat, Sprague-Dawley, 5 males and 5 females per concentration
Exposure route/Concentrations/Durations: Inhalation; 19, 39, 71, or 166 ppm for 4 h and 68, 155, 342, or 643 for 1 h
Effects:
19 ppm: no deaths or clinical signs; lung lesions ranged from mild infiltrate of inflammatory cells to congestion and edema.
39 ppm: 1/10 deaths; atelectasis in two lungs; bronchial lesions ranging from fibrosis to necrosis.
71 ppm: 7/10 deaths; necrotic bronchiolitis, congestion, edema, and hemorrhage in lungs.
166 ppm: 10/10 deaths; marked to severe necrotic bronchiolitis; moderate to marked vascular and inflammatory changes in all lungs.
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×
End point/Concentration/Rationale: Calculated LC01 values
Uncertainty factors/Rationale:
Interspecies: 3, rats, mice, and hamsters had similar clinical signs and the rate of mortality was similar among rats and mice in a subchronic study (Dow Corning Corp. 1981).
Intraspecies: 10, no data were available to estimate human variability and it was not clear that trimethoxysilane acts as a simple chemical irritant in the lungs (NRC 2001).
Modifying factor: Not applicable
Animal-to-human dosimetric adjustment: Not applicable
Time scaling: Cn × t = k (ten Berge et al. 1986), where n = 1.45
Data adequacy: Adequate for deriving AEGL-3 values
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

APPENDIX C

DERIVATION OF AEGL VALUES FOR TETRAMETHOXYSILANE

Derivation of AEGL-1 Values

Inadequate data exist for deriving AEGL-1 values for tetramethoxysilane.

Derivation of AEGL-2 Values

Key study: Kolesar, G.B., W.H. Siddiqui, R.G. Geil, R.M. Malczewski, and E.J. Hobbs. 1989. Subchronic inhalation toxicity of tetramethoxysilane in rats. Fundam. Appl. Toxicol. 13(2):285-295.
Toxicity end point: No-effect level for irreversible effects of 15 ppm
Time scaling: Cn × t = k
n = 3 for extrapolating to 30 min, 1 h, and 4 h
(15 ppm)3 × 6 h = 20,250 ppm

n = 1 for extrapolating to 8-h
(15 ppm)1 × 6 h = 90 ppm

Uncertainty factors: 3 for interspecies differences
10 for intraspecies variability
10-min AEGL-2: 1.1 ppm (6.8 mg/m3)
Set equivalent to 30-min AEGL-2 value because extrapolating from 4 h to 10 min is not recommended (NRC 2001)
30-min AEGL-2: C3 × 0.5 h = 20,250 ppm-h
C3 = 40,500 ppm
C = 34.34 34.34 ÷ 30 = 1.1 ppm (6.8 mg/m3)
1-h AEGL-2: C3 × 1 h = 20,250 ppm-h
C3 = 20,250 ppm
C = 27.26 ppm
27.26 ppm ÷ 30 = 0.91 ppm (5.6 mg/m3)
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×
4-h AEGL-2: C3 × 4 h = 20,250 ppm-h
C3 = 5,062.5 ppm
C = 17.17
17.17 ppm ÷ 30 = 0.57 ppm (3.5 mg/m3)
8-h AEGL-2: C1 × 8 h = 90 ppm-h
C1 = 11.25 ppm
11.25 ppm ÷ 30 = 0.38 ppm (2.4 mg/m3)

Derivation of AEGL-3 Values

Key study: Dow Corning Corp. 1992. Initial Submission: The Acute Vapor Inhalation Toxicity of Tetramethoxysilane and Trimethoxysilane with Rats (Final Report) with Cover Letter Dated 040992. Document ID No. 88920001842; Microfiche No. OTS0539103.
Toxicity end point: 4-h LC50 rat data; a BMCL05 of 26 ppm was used as the point of departure for AEGL-3 values (EPA Benchmark Calculation Dose Software, Version 1.3.2)
Time scaling: Cn × t = k
n = 3 for extrapolating to 30-min and 1-h
(26 ppm)3 × 4 h = 70,000 ppm

n = 1 for extrapolating to 8-h
(26 ppm)1 × 4 h = 104 ppm

Uncertainty factors: 3 for interspecies differences
10 for intraspecies variability
10-min AEGL-3: 1.7 ppm (11 mg/m3)
Set equivalent to 30-min AEGL-3 value because extrapolating from 4 h to 10 min is not recommended (NRC 2001)
30-min AEGL-3: C3 × 0.5 h = 70,000 ppm-h
C3 = 140,000 ppm
C = 52
52 ÷ 30 = 1.7 ppm (11 mg/m3)
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×
1-h AEGL-3: C3 × 1 h = 70,000 ppm-h
C3 = 70,000 ppm
C = 41 ppm
41 ppm ÷ 30 = 1.4 ppm (8.7 mg/m3)
4-h AEGL-3: C = 26 ppm
26 ppm ÷ 30 = 0.87 ppm (5.4 mg/m3)
8-h AEGL-3: C1 × 8 h = 104 ppm-h
C1 = 13 ppm
C = 13 ppm
13 ppm ÷ 30 = 0.43 ppm (2.7 mg/m3)
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

APPENDIX D

ACUTE EXPOSURE GUIDELINE LEVELS FOR TETRAMETHOXYSILANE

Derivation Summary for Tetramethoxysilane

AEGL-1 VALUES

Inadequate data exist for deriving AEGL-1 values for tetramethoxysilane. Absence of AEGL-1 values does not indicate that exposure below AEGL-2 values is safe.

AEGL-2 VALUES

10 min 30 min 1 h 4 h 8 h
1.1 ppm 1.1 ppm 0.91 ppm 0.57 ppm 0.38 ppm
Key reference: Kolesar, G.B., W.H. Siddiqui, R.G. Geil, R.M. Malczewski, and E.J. Hobbs. 1989. Subchronic inhalation toxicity of tetramethoxysilane in rats. Fundam. Appl. Toxicol. 13(2):285-295.
Test species/Strain/Number: Rat, Sprague-Dawley, 10 males and 10 females per concentration
Exposure route/Concentrations/Durations: Inhalation; 0, 1, 5, or 10 ppm (Phase 1) and 0, 15, 30, or 45 ppm (Phase 2); 6 h/day, 5 days/week for 28 days
Effects:
45 ppm: mortality (20/20)
30 ppm: ulceration in nasal cavity (18/20), squamous lung metaplasia (15/20), bilateral corneal desquamation of epithelium.
15 ppm: no lung lesions, minimal acute keratitis in corneal epithelium. ≤ 10 ppm: no lesions.
End point/Concentration/Rationale: 15 ppm was the no-effect level for irreversible effects
Uncertainty factors/Rationale:
Interspecies: 3, rats, mice, and hamsters had similar clinical signs and the rate of mortality was similar among rats and mice in a subchronic study of trimethoxysilane, a structural analog of tetramethoxysilane (Dow Corning Corp. 1981).
Intraspecies: 10, no data were available to estimate human variability and it was not clear that tetramethoxysilane acts as a simple chemical irritant in the lungs (NRC 2001).
Modifying factor: Not applicable
Animal-to-human dosimetric adjustment: Not applicable
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×
Time scaling: Cn × t = k (ten Berge et al. 1986), where n = 3 for extrapolation to 30 min, 1 h, and 4 h and n = 1 for extrapolation to 8 h. The 30-min AEGL-2 value was adopted as the 10-min value because extrapolating from 4 h to 10 min is not recommended (NRC 2001).
Data adequacy: Adequate for deriving AEGL-2 values

AEGL-3 VALUES

10 min 30 min 1 h 4 h 8 h
1.7 ppm 1.7 ppm 1.4 ppm 0.87 ppm 0.43 ppm
Key reference: Dow Corning Corp. 1992. Initial Submission: The Acute Vapor Inhalation Toxicity of Tetramethoxysilane and Trimethoxysilane with Rats (Final Report) with Cover Letter Dated 040992. Document ID No. 88-920001842; Microfiche No. OTS0539103.
Test species/Strain/Number: Rat; Sprague-Dawley; 10 males per concentration
Exposure route/Concentrations/Durations: Inhalation; 31, 50, or 88 ppm for 4 h
Effects:
31 ppm: no deaths or no clinical signs.
50 ppm: 3/10 deaths, gasping/coughing post exposure, lung damage.
88 ppm: 9/10 deaths, gasping/coughing post exposure, more wide-spread lung damage.
End point/Concentration/Rationale: Lethality; BMCL05 of 26 ppm determined using EPA Benchmark Database Software
Uncertainty factors/Rationale:
Interspecies: 3, rats, mice, and hamsters had similar clinical signs and the rate of mortality was similar among rats and mice in a subchronic study of trimethoxysilane, a structural analog of tetramethoxysilane (Dow Corning Corp. 1981).
Intraspecies: 10, no data were available to estimate human variability and it was not clear that tetramethoxysilane acts as a simple chemical irritant in the lungs (NRC 2001).
Modifying factor: Not applicable
Animal-to-human dosimetric adjustment: Not applicable
Time scaling: Cn × t = k (ten Berge et al. 1986), where n = 3 for extrapolation to 30 min and 1 h and n = 1 for extrapolation to 8 h. The 30-min AEGL-3 value is adopted as the 10-min value because extrapolating from 4 h to 10 min is not recommended (NRC 2001).
Data adequacy: Adequate for deriving AEGL-3 values
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

APPENDIX E

TIME SCALING FOR TRIMETHOXYSILANE

The relationship between dose and time for any given chemical is a function of the physical and chemical properties of the substance and its toxicologic and pharmacologic properties. Historically, the relationship according to Haber (1924), commonly called Haber’s Law (NRC 1993) or Haber’s Rule (C × t = k, where C = exposure concentration, t = exposure duration, and k = a constant) has been used to relate exposure concentration and duration to effect (Rinehart and Hatch 1964). According to this concept, exposure concentration and exposure duration may be reciprocally adjusted to maintain a cumulative exposure constant (k) and this cumulative exposure constant will always reflect a specific quantitative and qualitative response. This inverse relationship of concentration and time may be valid when the toxic response to a chemical is dependent equally on the concentration and the exposure duration.

However, an assessment by ten Berge et al. (1986) of LC50 data for certain chemicals revealed chemical-specific relationships between exposure concentration and exposure duration that were often exponential. The relationship can be expressed by the equation Cn × t = k, where n represents a chemical-specific, and even a toxic-end-point specific, exponent. The relationship described by this equation is basically the form of a linear regression analysis of the log-log transformation of a plot of C vs. t. ten Berge et al. (1986) examined the airborne concentration (C) and short-term exposure duration (t) relationship relative to death for approximately 20 chemicals and found that the empirically derived value of n ranged from 0.8 to 3.5 among this group of chemicals. Hence, the value of the exponent (n) in the equation Cn × t = k quantitatively defines the relationship

image

FIGURE E-1 Regression Plot of LC50 Values in Rats from Study by Nachreiner and Dodd (1988).

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

between exposure concentration and exposure duration for a given chemical and for a specific health-effect end point. Haber's Rule is the special case where n = 1. As the value of n increases, the plot of C vs. t yields a progressive decrease in the slope of the curve.

To calculate n for trimethoxysilane, a regression plot of LC50 values was derived using the concentration specific 60- and 240-min LC50 values in rats reported by Nachreiner and Dodd (1988). The LC50 values were analyzed using a linear regression analysis of the log-log transformation of a plot of C vs. t to derive a value of n for trimethoxysilane (see Figure E-1). The value of n for trimethoxysilane is 1.45.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

APPENDIX F

CATEGORY PLOTS FOR TRIMETHOXYSILANE AND TETRAMETHOXYSILANE

image

FIGURE F-1 Category plot of toxicity data and AEGL values for trimethoxysilane.

image

FIGURE F-2 Category plot of toxicity data and AEGL values for tetramethoxysilane.

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

APPENDIX G

BENCHMARK CALCULATIONS FOR TETRAMETHOXYSILANE

The benchmark calculations for tetramethoxysilane are based on a 4-h acute LC50 inhalation study (Dow Corning Corp. 1992). For the derivation of AEGL-3, the BMCL05 of 26 ppm was used.

BMCL05 = 26 ppm

BMC01 = 30 ppm

Probit Model $Revision: 2.1 $ $Date: 2000/02/26 03:38:53 $
Input Data File: C:\BMDS\DATA\TETRAMETHOXYSILANE.(d)
Gnuplot Plotting File: C:\BMDS\DATA\TETRAMETHOXYSILANE.plt
Thu Jan 12 10:41:03 2006
BMDS MODEL RUN
The form of the probability function is:
P[response] = Background
+ (1-Background) * CumNorm(Intercept+Slope*Log(Dose))
where, CumNorm(.) is the cumulative normal distribution function
Dependent variable = COLUMN3
Independent variable = COLUMN1
Slope parameter is not restricted
Total number of observations: 3
Total number of records with missing values: 0
Maximum number of iterations: 250
Relative Function Convergence has been set to: 1E-008
Parameter Convergence has been set to: 1E-008
User has chosen the log transformed model
Default Initial (and Specified) Parameter Values
   Background
   Intercept
   Slope
= 0
= -11.5792
= 2.85911
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

Asymptotic Correlation Matrix of Parameter Estimates

Intercept Slope Intercept Slope
Intercept 1 -1
Slop -1 1

(***The model parameter(s) background has been estimated at a boundary point, or has been specified by the user, and do not appear in the correlation matrix).

Parameter Estimates

Variable Estimate Standard error
Background 0 NA
Intercept -14.29 4.18256
Slope 3.49447 1.02457

NA: indicates that this parameter has hit a bound implied by some inequality constraint and thus has no standard error.

Analysis of Deviance Table

AIC: 23.0107

Goodness of Fit

Chi-square = 0.18; DF = 1; P-value = 0.6683

Benchmark Dose Computation

Specified effect
Risk Type
Confidence level    
BMD
BMDL
= 0.05
= Extra risk
= 0.95
= 37.2855
= 25.9763
Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
×

image

Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Suggested Citation:"7 Trimethoxysilane and Tetramethoxysilane." National Research Council. 2012. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13. Washington, DC: The National Academies Press. doi: 10.17226/15852.
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Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13 Get This Book
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At the request of the Department of Defense and the Environmental Protection Agency, the National Research Council has reviewed the relevant scientific literature compiled by an expert panel and established Acute Exposure Guideline Levels (AEGLs) for several chemicals. AEGLs represent exposure levels below which adverse health effects are not likely to occur and are useful in responding to emergencies, such as accidental or intentional chemical releases in community, workplace, transportation, and military settings, and for the remediation of contaminated sites.

Three AEGLs are approved for each chemical, representing exposure levels that result in: 1) notable but reversible discomfort; 2) long-lasting health effects; and 3) life-threatening health impacts. Acute Exposure Guideline Levels for Selected Airborne Chemicals: Volume 13 includes AEGLs for boron trifluoride, bromoacetone, chloroacetone, hexafluoroacetone, perchloryl fluoride, piperidine, propargyl alcohol, trimethoxysilane and tetramethoxysilane, and trimethylbenzenes.

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