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Toxicological Risks of Selected Flame-Retardant Chemicals 6 Alumina Trihydrate THERE are limited toxicokinetic and toxicity data available on alumina trihydrate. Therefore, this chapter reviews the physical and chemical properties, toxicokinetics, toxicological, epidemiological and exposure data on alumina trihydrate and a number of chemically related aluminum compounds. The bioavailability of aluminum is dependent upon its form, however, the underlying mechanism of toxicity appears to be similar among the different forms (with the exception of aluminum phosphide for which the toxicity is associated with phosphine gas). The effect of bioavailability of the various forms of aluminum on toxicity is discussed in the Quantitative Risk Assessment and the Exposure Assessment and Risk Characterization sections. The subcommittee used that information to characterize the health risk from exposure to alumina trihydrate. The subcommittee also identified data gaps and recommended research relevant for determining the health risk from exposure to alumina trihydrate. PHYSICAL AND CHEMICAL PROPERTIES The physical and chemical properties of alumina trihydrate are summarized in Table 6–1.
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Toxicological Risks of Selected Flame-Retardant Chemicals TABLE 6–1 Physical and Chemical Properties for Alumina Trihydrate Characteristic Value Reference Chemical formula Al(OH)3 Lide 1991–1992 CAS registry # 21645–51–2 Lide 1991–1992 Synonyms aluminum hydroxide, aluminum hydrate, hydrated alumina Budavari et al. 1989 Molecular weight 77.99 Lide 1991–1992 Physical state White powder Budavari et al. 1989 Solubility Insoluble in hot or cold water; soluble in acid and alkali; insoluble in alcohol Lide 1991–1992 Melting point 300°C Lide 1991–1992 Density 2.42 at 25°C Lide 1991–1992 OCCURRENCE AND USE Alumina trihydrate is used as a flame retardant both within and outside the U.S. in the interiors of automobiles, commercial upholstered furniture, draperies, wall coverings and carpets (R.C.Kidder, Flame Retardant Chemical Association, unpublished material, April 21, 1998). It is also used in detergents, antiperspirants, and cosmetics, and used therapeutically as an antacid (e.g., Maalox) and to control phosphate levels. TOXICOKINETICS Absorption Dermal Exposure No data were found on the dermal absorption of alumina trihydrate. However, two reports were found on the dermal absorption of aluminum chloride. Dermal application of aqueous aluminum chloride (0.025–0.1 µg/cm2) to shaved Swiss mice increased urine, serum, and whole brain aluminum concentrations (Anane et al. 1995). Dermal application (0.4 µg/d; 20 d of gestation) of aluminum chloride to pregnant Swiss mice resulted in elevated aluminum concentrations in the serum and organs of the dams and fetuses, and in the amniotic fluid (Anane et al. 1997).
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Toxicological Risks of Selected Flame-Retardant Chemicals Inhalation Exposure Workers exposed to aluminum dust or fumes had higher urinary aluminum concentrations at the end of a work shift than a control group (Mussi et al. 1984). Plasma aluminum concentrations, however, were not increased. Serum and urinary aluminum concentrations increased in three individuals not previously exposed to aluminum-containing welding fumes following an 8-hr exposure to those fumes (average exposure of 2.4 mg aluminum/m3) (Sjögren et al. 1985). Sjögren et al. (1988) reported that workers exposed to aluminum from welding fumes had elevated aluminum concentrations in their urine, and that a 16 to 37-d break from exposure resulted in decreased urinary aluminum concentrations (median levels decreased from 54 µg/g creatinine to 29 µg/g creatinine). Serum and urinary aluminum concentrations were higher in workers exposed to aluminum (25 µg/m3 respirable particles; 100 µg/m3 total particles) compared with pre-shift concentrations and concentrations in unexposed controls (Gitelman et al. 1995). The percentage of aluminum absorbed was not determined in those studies. No relevant animal data were identified on absorption of aluminum following inhalation exposure. Oral Exposure The bioavailability of orally administered aluminum is related to the form in which it is ingested and the presence of dietary constituents with which the metal can complex. Ligands in food can have a marked effect on absorption of aluminum; they can either enhance uptake by forming absorbable (usually water-soluble) complexes (e.g., with carboxylic acids such as citric acid or lactic acid), or reduce absorption by forming insoluble compounds (e.g., with phosphate or dissolved silicate). In humans, evidence suggests that the most important compound that aluminum complexes with that increases aluminum uptake is citric acid (or its conjugate base citrate). Citric acid is a constituent of many foods and beverages, and can be present in the gut at high concentrations (Reiber et al. 1995). Concomitant exposure to aluminum-containing antacids and orange juice caused a 10-fold increase in absorption of aluminum as compared to exposure to antacids alone (Fairweather-Tait et al. 1994). Milk had no effect on aluminum absorption in that study. Volunteers (n=7–10) who ingested antacids containing 976 mg of alumina trihydrate (approximately 14 mg/kg) absorbed 0.004%, 0.03%, or 0.2% of the aluminum when the antacids were suspended in tap water (pH 9.2), orange juice (pH 4.2), or citric acid (pH 2.4), respectively (Weberg
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Toxicological Risks of Selected Flame-Retardant Chemicals and Berstad 1986). Priest et al. (1996, as cited in ATSDR 1999) measured aluminum absorption in two male volunteers following administration of a single dose of Al-labeled aluminum citrate (aqueous solution) or alumina trihydrate (colloidal suspension in water) directly into the stomach; 0.5% of the aluminum in aluminum citrate and 0.01% of the aluminum in alumina trihydrate were absorbed. In that same study (Priest et al. 1996, as cited in ATSDR 1999), 0.14% of the aluminum was absorbed after concomitant exposure to alumina trihydrate and trisodium citrate; that exposure scenario is similar to ingestion of aluminum in orange juice. Urinary and plasma aluminum concentrations were significantly higher in women treated with calcium citrate than when they were not treated with calcium citrate, indicating that dietary factors can affect the uptake of aluminum from normal diets (Nolan et al. 1994, as cited in ATSDR 1999). Infants are able to absorb orally administered aluminum. Plasma aluminum concentrations increased (from 0.64 µmol/L prior to treatment to 3.48 µmol/L after treatment) in 7 infants treated with aluminum-containing antacids (400–800 µmol aluminum for 2 d) (Chedid et al. 1991). Individuals with young senile dementia of the Alzheimer’s type (Taylor et al. 1992) and individuals with Down’s Syndrome (Moore et al. 1997) appear to have increased absorption of aluminum. Evidence in animals indicates that absorption of aluminum is low following oral exposure, and that the form of aluminum ingested and dietary factors can affect aluminum absorption. Only 0.97% of the dose was absorbed in rats gavaged with AlCl3 (n=3/group) (Zafar et al. 1997). Following a single gavage dose of alumina trihydrate, aluminum citrate, aluminum citrate with sodium citrate added, or aluminum maltolate, 0.1%, 0.7%, 5.1%, and 0.1% of the aluminum was absorbed, respectively (Schonholzer et al. 1997). Jouhanneau et al. (1997) measured skeletal retention and urinary excretion of aluminum, as an indication of absorption, in 2-mo-old Wistar rats fed aluminum in the diet. In the absence of citrate, 0.05% of the aluminum dose was found in the urine and in the skeleton. The presence of citrate in the diet increased excretion by two- to five-fold (Jouhanneau et al. 1997). Plasma, bone, kidney, cerebral cortical, and cerebellar aluminum concentrations were not increased (compared to untreated controls) in rats fed alumina trihydrate alone, but were increased in rats fed an equivalent concentration of aluminum complexed with citrate, lactate, malate, or tartrate (Testolin et al. 1996). Domingo et al. (1993) investigated the effect of dietary constituents on the absorption of aluminum from the normal diet. The addition of lactic, tartaric, gluconic, malic, succinic, ascorbic, citric, or oxalic acid to drinking water increased the concentration of aluminum in the bone; all except succinic and ascorbic acid increased aluminum concentrations in the brain. Prolonged fasting increased the absorption of aluminum in Wistar rats (Drueke et al. 1997).
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Toxicological Risks of Selected Flame-Retardant Chemicals Based on the data discussed above, it was concluded that alumina trihydrate is more poorly absorbed than other aluminum compounds. Some data indicate a direct linear relationship between the dose of soluble aluminum and the plasma aluminum level (Partridge et al. 1992, as cited in ATSDR 1999). However, the data on both solubility and bioavailability are inadequate to reliably extrapolate quantitatively from solubility in water to bioavailability, especially with the effects of dietary constituents. Distribution and Metabolism Dermal Exposure Following dermal absorption, aluminum chloride distributes to the brain in Swiss mice (Anane et al. 1995) and to the fetus in pregnant Swiss mice (Anane et al. 1997). Inhalation Exposure Autopsy results of men chronically exposed to aluminum via inhalation indicated that aluminum distributes to the lungs, liver, and spleen (Teraoka 1981). Rabbits exposed to low concentrations of aluminum dust (Al2O3; 1/20th of the threshold limit value) had 2.5-times higher concentrations of aluminum in the brain compared to controls. Serum concentrations were only slightly increased and concentrations in other tissues were not elevated (Rollin et al. 1991). Rats exposed via inhalation to aluminum acetylacetonate also demonstrated an accumulation of aluminum in the brain (Zatta et al. 1993). Oral Exposure Following gavage in rats, the highest accumulation of aluminum is in the bone, followed by the spleen, kidneys and liver, and brain (Zafar et al. 1997). Testolin et al. (1996) also demonstrated that aluminum distributes to the bone, kidneys, cerebral cortex, and cerebellum. Other Routes of Exposure Yokel and McNamara (1989) investigated the distribution and half-life of aluminum in rabbits after a 6-hr intravenous infusion. Aluminum concentra-
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Toxicological Risks of Selected Flame-Retardant Chemicals tions were increased in the bile, kidneys, liver, lungs, serum, and spleen after 4 hr, but not in the brain. The half-life was tissue-dependent, ranging from 12 hr in the bile to 113 d in the spleen. After intravenous injection of aluminum lactate or aluminum citrate in rats and rabbits, aluminum appeared to freely diffuse into liver, but was lower in the brain than the blood, indicating that there is a partial barrier to aluminum entry into the brain (Yokel et al. 1991). Further research, however, indicates that an active process pumps aluminum out of the brain following administration of aluminum citrate (Yokel et al. 1994; Allen et al. 1995; Ackley and Yokel 1997). Regardless of the route of exposure, once absorbed and distributed in the body, aluminum can exist in different forms. Low concentrations of aluminum exist as free ions. Aluminum can also complex with organic acids, amino acids, nucleotides, phosphates, and carbohydrates. Aluminum can form reversible and practically irreversible complexes with proteins, polynucleotides, and glycosaminoglycans (Ganrot 1986). Excretion Dermal Exposure Aluminum was detected in the urine of Swiss mice following dermal exposure to aluminum chloride (Anane et al. 1995). Inhalation Exposure Following inhalation exposure, absorbed aluminum is primarily excreted via the urine. Excretion half-lives of 7.5 and 8 hr have been reported in workers exposed to aluminum from welding fumes (Sjögren et al. 1985; Pierre et al. 1995). The urinary excretion half-life appears to rise with increasing exposure duration (Sjögren et al. 1985). Urinary aluminum concentrations in workers exposed to aluminum were more than 10 times higher than those of individuals not exposed to aluminum in the workplace, and remained elevated many years after the occupational exposure ceased (Elinder et al. 1991). Oral Exposure The majority of ingested aluminum is excreted in the feces without being absorbed systemically (Gorsky et al. 1979; Jouhanneau et al. 1997). Absorbed
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Toxicological Risks of Selected Flame-Retardant Chemicals aluminum is primarily excreted in the urine (Kaehny et al. 1977; Recker et al. 1977; Gorsky et al. 1979; Greger and Baier 1983). HAZARD IDENTIFICATION1 Dermal Exposure Irritation Skin rashes in sensitive individuals are the only adverse effects observed in humans dermally exposed to aluminum compounds (ATSDR 1999). Damage to the skin was observed in mice, rabbits, and pigs following exposure to 10% aluminum chloride and aluminum nitrate for 5 d. No dermal effects were observed in animals exposed to 10% alumina trihydrate, aluminum sulfate, aluminum acetate, or aluminum chlorohydrate (Lansdown 1973, as cited in ATSDR 1999). Systemic Effects No studies were identified that report immunological, neurological, reproductive, developmental, carcinogenic, or other systemic effects of aluminum following dermal exposure. Inhalation Exposure Systemic Effects No studies were identified that investigated the effects of alumina trihydrate via inhalation exposure. Pulmonary fibrosis is the most common respiratory effect in workers exposed to finely ground aluminum dust (pyropowder) (Ueda et al. 1958; Edling 1961; Mitchell et al. 1961; McLaughlin et al. 1962). However, that effect appears to be associated with a specific type of oil coating on the aluminum dust (Crombie et al. 1944; Meiklejohn and Posner 1957; Posner and Kennedy 1967). Case reports indicate that inhalation exposure to various 1 In this section, the subcommittee reviewed the toxicity data of alumina trihydrate, including the toxicity assessment prepared by the U.S. Consumer Product Safety Commission (Ferrante 1999).
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Toxicological Risks of Selected Flame-Retardant Chemicals forms of aluminum leads to pulmonary toxicity (Chen et al. 1978; Miller et al. 1984; Park et al. 1996, as cited in ATSDR 1999; Vandenplas et al. 1998). In a study of 17 occupationally exposed individuals, pulmonary fibrosis was associated with inhalation exposure to aluminum silicate dust (Musk et al. 1980). Avolio et al. (1989) reported interstitial fibrosis following inhalation exposure to aluminum. Those occupational studies are limited by concomitant exposures to other chemicals and cigarettes. However, in one study of nonsmoking individuals occupationally exposed to aluminum compounds (14 exposed; 28 controls) there were indications of increased alveolar capillary permeability and activation of alveolar macrophage in bronchoalveolar lavage, but no evidence of restrictive lung disease (Eklund et al. 1989). Granulomatous reactions (at concentrations of 2.5 and 25 mg/m3 aluminum chlorohydrate), decreases in body weight (at concentrations of 25 mg/m3), and increases in lung to body weight ratios (at concentrations of 25 mg/m3) were seen in rats and guinea pigs exposed to aluminum chlorohydrate for 6 mo (Steinhagen et al. 1978). Exposure of female Wistar rats to aluminum fibers for 86 wk resulted in minimal pulmonary reactions (Pigott et al. 1981). Neurological Effects Subclinical neurological effects have been observed in workers chronically exposed to aluminum dust, welding fumes, and McIntyre powder (finely ground aluminum and aluminum oxide) (Hosovski et al. 1990; Rifat et al. 1990; White et al. 1992; Bast-Pettersen et al. 1994; Hänninen et al. 1994; Sjögren et al. 1996; Dick et al. 1997; Sim et al. 1997). Those effects include changes in neurobehavioral test performance (e.g., eye-hand coordination, reaction time, cognitive tests) and increased incidences of subjective symptoms (e.g., incoordination, depression, fatigue). A role of aluminum has been hypothesized in the etiology of Alzheimer’s disease (AD). However, in an unmatched case-control study (198 AD cases; 340 controls made up of 164 individuals with non-AD dementias and 176 individuals with no dementias), no significant association (odds ratio=0.98) between occupational aluminum exposure and AD was reported (Salib and Hillier 1996). Cancer There are a number of epidemiological studies on cancer incidence in workers in aluminum reduction plants (Gibbs and Horowitz 1979; Milham 1979;
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Toxicological Risks of Selected Flame-Retardant Chemicals Theriault et al. 1981; Rockette and Arena 1983; Gibbs 1985; Armstrong et al. 1986; Spinelli et al. 1991). In a review of many of those studies, Ronneberg and Langmark (1992) concluded that some data were suggestive of an increased risks for specific cancers for workers in aluminum reduction plants. However, those conclusions were limited by inadequate information on smoking and exposure to other carcinogenic compounds, including asbestos and polycylic aromatic hydrocarbons. In a retrospective cohort study that was initiated because of a cluster of pituitary adenoma cases (four cases over 5 yr), there was no indication of an increased risk for pituitary adenoma at an aluminum production factory (Cullen et al. 1996). There was no overall excess risk for cancer and no excess risk for bladder or liver cancer among men or women workers in aluminum foundries and scrap aluminum smelters in Sweden (n=6,454) (Selden et al. 1997). However, risk estimates for lung cancer in males (standardized incidence ratio [SIR] =1.49), anorectal cancer (SIR=2.13), and sinonasal cancer (SIR=4.70) were increased. Socioeconomic status appeared to underlie the increased risk of lung cancer, except for individuals employed in the sand casting of aluminum for 10 yr or more. Epidemiological studies of workers in aluminum smelters report an increased mortality from malignant lung neoplasm, however, many of the workers had evidence of co-exposure to asbestos, silicates, and metal-rich nonfibrous particles, such as chromium and cobalt (Dufresne et al. 1996), or polycyclic aromatic hydrocarbons (Armstrong et al. 1994). In the only animal study investigating the carcinogenic potential of inhaled aluminum compounds, there was no evidence of an increased incidence of tumors in the lungs of male or female Wistar rats exposed to aluminum fibers (2.18–2.45 mg aluminum/m3; 96% aluminum oxide) for 86 wk (Pigott et al. 1981). Other Systemic Effects No studies were identified on the immunological, reproductive, or developmental effects following inhalation of aluminum. Oral Exposure Systemic Effects Aluminum compounds have low acute toxicity because of their low solubility. The maximum tolerated daily dose for alumina trihydrate in a healthy, 70-
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Toxicological Risks of Selected Flame-Retardant Chemicals kg adult is 50 to 128 mg/kg (17.5–45 mg aluminum/kg) (Poisindex 1998). Constipation, diarrhea, distension, and/or obstruction with perforation have been reported in individuals on chronic antacid therapy. However, the role of aluminum in that effect is not known (HSDB 1990). Individuals with chronic renal failure who ingest large amounts of aluminum trihydrate to treat hyperphosphatemia can accumulate aluminum in the body, resulting in hypercalcemia, microcytic anemia, proximal myopathy, osteomalacia, and progressive dialysis encephalopathy (Sideman and Manor 1982; HSDB 1990; Ellenhorn 1997). Osteomalacia has also been observed in healthy children treated with aluminum-containing antacids for colic (Pivnick et al. 1995). Preterm infants are at risk for aluminum toxicity from ingestion of some infant formulas that contain aluminum compounds, and from aluminum-containing parenteral nutrition solutions (Sedman et al. 1985; Koo et al. 1992; Golub and Domingo 1996). There is an extensive oral toxicity database in animals, but many of the studies are limited by a lack of information on background concentrations of aluminum compounds in the diet. Commercial grain-based feeds for laboratory animals contain high concentrations of aluminum compounds which can contribute substantially to total aluminum exposure. The background aluminum concentrations in feed, therefore, should be considered when assessing the toxicity of aluminum compounds. A summary of the studies is presented in Table 6–2. Most aluminum compounds have LD50s in the range of 1–4 g aluminum/kg (Poisindex 1998). No significant effects on mortality or body weight were observed in Sprague-Dawley rats fed 989 or 1,070 µg aluminum/g of food (as alumina trihydrate; calculated to be equivalent to approximately 158 mg aluminum/kg-d) for 16 d (background concentrations, 9–26 µg aluminum/g food) (Greger and Donnaubauer 1986). Hicks et al. (1987) reported no significant alterations in hematology, clinical chemistry, histopathology, or organ weights in Sprague-Dawley rats fed 302 mg aluminum/kg-d as alumina trihydrate in the diet for 28 d (background concentration, 66 ppm; reported as 5 mg aluminum/kg-d). In general, subchronic and chronic studies in mice and rats examining a number of systemic end points do not demonstrate adverse effects following dietary or drinking water exposure to aluminum. Oteiza et al. (1993) fed Swiss-Webster mice 1,000 µg aluminum/g in food (background levels; 3 mg aluminum/g food) as aluminum chloride for 5 or 7 wk. No systemic effects were seen. Oneda et al. (1994) fed male and female B6C3F1 mice 1%, 2.5%, 5%, or 10% aluminum potassium sulfate for 20 mo and reported a decrease in liver weight (5–10%), and an increase in kidney weight (2.5%) and heart weight (5%). Relative organ weight and blood parameters were not affected in
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Toxicological Risks of Selected Flame-Retardant Chemicals TABLE 6–2 Selected Toxicity Studies of Orally Administered Alumina Compoundsa Animal Species and Strain/Aluminum Compound/Duration of Exposure Dose (mg Al/kg-d) Effects NOAEL (mg Al/kg-d) LOAEL (mg Al/kg-d) Reference Systemic toxicity Female Sprague-Dawley rats; aluminum nitrate (drinking water); 100 d 25 (control), 51, 77, 284 None 284 ND Domingo et al. 1987a Sprague-Dawley rats; aluminum trihydrate (diet); 28 d 5 (control), 302 None 302 ND Hicks et al. 1987 Female Sprague-Dawley rats; aluminum nitrate (drinking water) 1 mo 25 (control), 52, 79, 133 Hyperemia in the liver, periportal monocytic infiltrate in liver 79 133 Gomez et al. 1986 Sprague-Dawley rats; aluminum trihydrate (diet); 16 d 158 None 158 ND Greger and Donnaubauer 1986 Neurotoxicity Female Swiss-Webster mice; aluminum lactate (diet); 6 wk 3 (control), 62, 130 Decreased motor activity 62 130 Golub et al. 1989 Female Swiss-Webster mice; aluminum lactate (diet); 90 d 4.9 (control), 195 Decreased motor activity, hindlimb grip strength and startle responsiveness ND 195 Golub et al. 1992a Female Swiss-Webster mice; aluminum chloride and 3.5% sodium citrate (diet) 5–7 wk 0.6 (control), 195 Decreased forelimb and hindlimb grip strength ND 195 Oteiza et al. 1993
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Toxicological Risks of Selected Flame-Retardant Chemicals opmental toxicity. Although a multigeneration reproductive study was not identified, the available single-generation studies suggest that reproductive toxicity is not a sensitive end point. The database lacks studies that identify a NOAEL for neurodevelopmental effects and a study that adequately assesses potential differences in the toxicity of various aluminum compounds. Cancer The potential carcinogenicity of alumina trihydrate cannot be determined based on inadequate data for an assessment of carcinogenicity via the dermal, inhalation, and oral routes. EXPOSURE ASSESSMENT AND RISK CHARACTERIZATION Noncancer Dermal Exposure The assessment of noncancer risk by the dermal route of exposure is based on the scenario described in Chapter 3. This exposure scenario assumes that an adult spends 1/4th of his or her time sitting on furniture upholstery treated with alumina trihydrate, that 1/4th of the upper torso is in contact with the upholstery, and that clothing presents no barrier. Alumina trihydrate is considered to be ionic, and is essentially not absorbed through the skin. However, to be conservative, the subcommittee assumed that ionized alumina trihydrate permeates the skin at the same rate as water, with a permeability rate of 10−3 cm/hr (EPA 1992). Using that permeability rate, the highest expected application rate for alumina trihydrate (7.5 mg/cm2), and Equation 1 in Chapter 3, the subcommittee calculated a dermal exposure level of 5.9×10−2 mg/kg-d. The oral RfD for alumina trihydrate (1.5 mg/kg-d; see Oral RfD in Quantitative Toxicity section) was used as the best estimate of the internal dose for dermal exposure. Dividing the exposure level by the oral RfD yields a hazard index of 3.9×10−2. Thus it was concluded that alumina trihydrate used as a flame retardant in upholstery fabric is not likely to pose a noncancer risk by the dermal route. Inhalation Exposure Particles The assessment of the noncancer risk by the inhalation route of exposure is
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Toxicological Risks of Selected Flame-Retardant Chemicals based on the scenario described Chapter 3. This scenario corresponds to a person spending 1/4th of his or her life in a room with a low air-change rate (0.25/hr) and with a relatively large amount of fabric upholstery treated with alumina trihydrate (30 m2 in a 30-m3 room), with this treatment gradually being worn away over 25% of its surface to 50% of its initial quantity over the 15-yr lifetime of the fabric. A small fraction, 1%, of the worn-off alumina trihydrate is released into the indoor air as inhalable particles and may be breathed by the occupant. Equations 4 through 6 in Chapter 3 were used to estimate the average concentration of alumina trihydrate present in the air. The highest expected application rate for alumina trihydrate is about 7.5 mg/cm2. The estimated release rate for alumina trihydrate is 2.3×10−7/d. Using those values, the estimated time-averaged exposure concentration for alumina trihydrate is 0.71 µg/m3. Although lack of sufficient data precludes deriving an inhalation RfC for alumina trihydrate, the oral RfD (1.5 mg alumina trihydrate/kg-d; see Oral RfD in Quantitative Toxicity Assessment section), which represents a very conservative estimate (see Chapter 4 for the rationale), was used to estimate an RfC of 5.25 mg/m3. Division of the exposure concentration (0.71 µg/m3) by the estimated RfC (5.25 mg/m3) results in a hazard index of 1.4×10−4, indicating that under the worst-case exposure scenario, exposure to alumina trihydrate, used as an upholstery fabric flame retardant, is not likely to pose a noncancer risk from exposure to alumina trihydrate particles. Vapors In addition to the possibility of release of alumina trihydrate in particles worn from upholstery fabric, the subcommittee considered the possibility of its release by evaporation. However, because of alumina trihydrate’s negligible vapor pressure at ambient temperatures, the subcommittee concluded that exposure to alumina trihydrate vapors from its use as an upholstery fabric flame retardant is not likely to pose a noncancer risk. Oral Exposure The assessment of the noncancer risk by the oral exposure route is based on the scenario described in Chapter 3. That exposure assumes a child is exposed to alumina trihydrate through sucking on 50 cm2 of fabric backcoated with alumina trihydrate daily for two yr, one hr/d. The highest expected application rate for alumina trihydrate is about 7.5 mg/cm2. A fractional rate (per unit
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Toxicological Risks of Selected Flame-Retardant Chemicals time) of alumina trihydrate extraction by saliva is estimated as 0.001/d, based on leaching of antimony from polyvinyl chloride cot mattresses (Jenkins et al. 1998). Using those assumptions and Equation 15 in Chapter 3, the average oral dose rate was estimated to be 0.0016 mg/kg-d. Division of that exposure estimate (0.0016 mg/kg-d) by the oral RfD (1.5 mg/kg-d; see Oral RfD in Quantitative Toxicity Assessment Section) results in a hazard index of 1.0×10−3. Therefore, under the worst-case exposure assumptions, alumina trihydrate, used as a flame retardant in upholstery fabric, is not likely to pose a noncancer risk by the oral exposure route. Cancer There are inadequate data to characterize the carcinogenic risk from exposure to alumina trihydrate from any route of exposure. RECOMMENDATIONS FROM OTHER ORGANIZATIONS The Agency for Toxic Substances and Disease Registry (ATSDR 1999) has established an intermediate-duration oral minimal risk level (MRL) for aluminum of 2.0 mg aluminum/kg-d. The Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for aluminum dust is 15 mg/m3 (for total dust) and 5 mg/m3 (for respirable dust) (OSHA 1974). The American Conference of Governmental Industrial Hygienists (ACGIH 1999) has set a Threshold Limit Value (TLV) for alumina trihydrate of 10 mg/m3. DATA GAPS AND RESEARCH NEEDS Although there are toxicity data on other aluminum compounds, data on aluminum trihydrate are lacking. In addition, chronic carcinogenic studies following dermal, inhalation, and oral exposure, and reproductive and developmental studies following dermal and inhalation exposure are lacking for any relevant aluminum compound. However, alumina trihydrate is used extensively in antacids (e.g., “Maalox”) and cosmetics, and the hazard indices are less than 1 for all routes of exposure using the subcommittee’s conservative assumptions. Therefore, the subcommittee concludes that further research is not needed to assess the health risks from alumina trihydrate when used as a flame-retardant chemical in furniture upholstery fabric.
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Representative terms from entire chapter: