8
Zinc Borate

THERE is limited information in the literature on the toxicity of zinc borate. Zinc borate readily breaks down in the stomach to zinc oxide (ZnO) and boric acid (H3BO3). Therefore, this chapter reviews the physical and chemical properties, toxicokinetics, toxicological, epidemiological, and exposure data on both those compounds. When data on zinc oxide are lacking, data on other zinc compounds are reviewed. According to the International Programme on Chemical Safety (IPCS), at low concentrations and under the same conditions, an equivalent amount of boron as boric acid or borax has similar chemical and toxicological properties (IPCS 1998). Therefore, data from boric acid and borax are considered in this chapter. Regardless of the zinc or boron compound of exposure, body burdens are measured as the concentration of the element (zinc or boron), and are discussed as such in this review. Doses are given in boron and zinc equivalents for comparison between different zinc and boron compounds.

The subcommittee used the toxicity, toxicokinetic, and exposure data on those compounds to characterize the health risk from exposure to zinc borate. The subcommittee also identified data gaps and recommended research relevant for determining the health risk from exposure to zinc borate.

PHYSICAL AND CHEMICAL PROPERTIES

The physical and chemical properties of zinc borate, zinc oxide, and boric acid are summarized in Table 8–1.



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Toxicological Risks of Selected Flame-Retardant Chemicals 8 Zinc Borate THERE is limited information in the literature on the toxicity of zinc borate. Zinc borate readily breaks down in the stomach to zinc oxide (ZnO) and boric acid (H3BO3). Therefore, this chapter reviews the physical and chemical properties, toxicokinetics, toxicological, epidemiological, and exposure data on both those compounds. When data on zinc oxide are lacking, data on other zinc compounds are reviewed. According to the International Programme on Chemical Safety (IPCS), at low concentrations and under the same conditions, an equivalent amount of boron as boric acid or borax has similar chemical and toxicological properties (IPCS 1998). Therefore, data from boric acid and borax are considered in this chapter. Regardless of the zinc or boron compound of exposure, body burdens are measured as the concentration of the element (zinc or boron), and are discussed as such in this review. Doses are given in boron and zinc equivalents for comparison between different zinc and boron compounds. The subcommittee used the toxicity, toxicokinetic, and exposure data on those compounds to characterize the health risk from exposure to zinc borate. The subcommittee also identified data gaps and recommended research relevant for determining the health risk from exposure to zinc borate. PHYSICAL AND CHEMICAL PROPERTIES The physical and chemical properties of zinc borate, zinc oxide, and boric acid are summarized in Table 8–1.

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Toxicological Risks of Selected Flame-Retardant Chemicals TABLE 8–1 Physical and Chemical Properties of Zinc Borate, Zinc Oxide, and Boric Acid   Value Property Zinc Borate Zinc Oxide Boric Acid Reference Chemical formula 3ZnO:2B2O3 ZnO H3BO3 Lide 1991–1992 CAS registry # 138265–88–0 1314–13–2 10043–35–3 Lide 1991–1992 Synonyms — Zinc white, pigment white Orthoboric acid, boracic acid, borofax Budavari et al. 1989 Molecular weight 383.4 81.4 61.3 Lide 1991–1992 Physical state Crystal or white powder Crystal or white powder Transparent crystals or white granules or powder Budavari et al. 1989 Solubility Soluble in cold water; crystal insoluble in HCl; amorphous soluble in HCl 0.00016 g/100 mL water at 29°C; soluble in acid, alkaline, ammonium chloride; insoluble in alcohol 6.35 g/100 mL water at 30°C; 27.6 g/100 mL water at 100°C Lide 1991–1992 Melting point 980°C 1,975°C 169°C±1 Lide 1991–1992 Octonal/water partition coefficient ND ND 0.175 IPCS 1998 Density Crystal: 4.22 g/cm3; Powder: 3.64 g/cm3 5.6 g/cm3 1.435 g/mL at 15°C Lide 1991–1992 Abbreviations: HCl, hydrochloric acid; ND, not determined OCCURRENCE AND USE Zinc borate is typically composed of 45% ZnO and 34% boric anhydride (B2O3), with 20% water of hydration. Zinc borate is used as a flame retardant

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Toxicological Risks of Selected Flame-Retardant Chemicals in conjunction with other chemicals, including antimony trioxide, magnesium hydroxide, alumina trihydrate, and some brominated flame retardants. Zinc borate is used as a flame retardant on commercial furniture, draperies, wall coverings, and carpets (R.C.Kidder, Flame Retardant Chemical Association, unpublished material, April 21, 1998). In addition, zinc borate is used as a fungicide. Zinc oxide is used as a pigment in paint, cosmetics, and dental and quick drying cements. Therapeutically, zinc oxide is used as an astringent and as a topical protectant. Boric acid is used in enamels, porcelain, soaps, cosmetics, and as an insecticide. Therapeutically, boric acid is used as an astringent and an antiseptic. TOXICOKINETICS Absorption Zinc Borate No studies were identified that investigate the toxicokinetics of zinc borate following dermal, inhalation, or oral exposure. Zinc Oxide Agren (1991) reported that zinc is present in human interstitial fluid at the site of application following dermal application of zinc oxide in gum resin or hydrocolloids to human forearms. No evidence for absorption into systemic circulation was provided. Zinc readily permeates intact and damaged human skin following dermal application; however, absorption of zinc into systemic circulation was not determined (Hallmans 1977; Agren 1990, as cited in ATSDR 1994; Agren et al. 1991, as cited in ATSDR 1994). Keen and Hurley (1977) determined that when zinc (as zinc chromate) was dissolved in oil and topically applied to rats, absorption of zinc into the bloodstream occurred. No other animal studies were identified that investigated the dermal absorption of zinc. Workers exposed occupationally (via inhalation) to zinc fumes (zinc compound not specified) had elevated blood zinc concentrations (Hamdi 1969). Exposure of cats to zinc oxide fumes for up to 3.25 hr resulted in increased concentrations of zinc in the pancreas, kidney, and liver (Drinker and Drinker 1928, as cited in ATSDR 1994). In both studies, oral absorption of zinc particles following ciliary clearance and swallowing could account for all, or a

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Toxicological Risks of Selected Flame-Retardant Chemicals significant portion, of the absorbed zinc. In the Drinker and Drinker (1928, as cited in ATSDR 1994) study, the swallowing of zinc particles during grooming activities might also account for the increased tissue zinc levels. No data are available on the oral absorption of zinc oxide. The estimated rate of oral absorption of zinc (all zinc compounds) in humans is between 8% and 81%, depending on an individual’s diet (ATSDR 1994). People who are not deficient in zinc absorb about 20–30%, while zinc-deficient individuals absorb more (ATSDR 1994). Two studies measured the peak blood concentrations of zinc in volunteers following oral ingestion of zinc sulfate; peak blood Zn2+ concentrations were reached within 3 hr (Neve et al. 1991; Sturniolo et al. 1991, as cited in ATSDR 1994). The presence of cadmium, mercury, copper, or other trace metals can diminish zinc absorption by inhibiting zinc transport across the intestinal wall (ATSDR 1994). Zinc absorption in male Wistar rats was approximately 40–48% when diets contained 0.81 mg of radio-labeled zinc (as zinc chloride or zinc carbonate) per kg of body weight (Galvez-Morros et al. 1992). ATSDR (1994) noted that the fraction of ingested zinc absorbed in immature organisms usually exceeds the fraction of ingested zinc absorbed in adult organisms. Boric Acid Wester et al. (1998) exposed the back of the hand of volunteers to a 5% aqueous solution of boric acid or borax and measured urinary boron concentrations to determine the extent of absorption, the flux, and the permeability constants (Kp) for intact skin. Following exposure to boric acid, 0.23% of the applied dose was excreted, flux was calculated as 0.01 µg/cm2/hr and Kp was 1.9×10−7 cm/hr. Following exposure to borax, 0.21% of the applied dose was excreted, flux was calculated as 0.01 µg/cm2/hr, and Kp was 1.8×10−7 cm/hr. Draize and Kelly (1959) has also reported low dermal absorption of boric acid, with no increase in urinary boron concentrations following a 4-hr exposure in a volunteer. Blood boron concentrations did not increase in infants after treatment with ointment (3% boric acid), indicating a lack of dermal absorption of boric acid (Friis-Hansen et al. 1982). No absorption of boric acid (measured as boron in the blood) occurred 1–9 d after a single topical application of boric acid in an anhydrous, water-emulsifying ointment (Stuttgen et al. 1982). However, blood boron concentrations were increased within 2–6 hr after application of the same amount of boric acid in a water-based jelly, indicating that the vehicle in which boric acid is applied to the skin affects absorption. Boron was detected in the urine of infants who had moderate to marked diaper rash, but not in the urine of infants who had minor or no diaper rash,

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Toxicological Risks of Selected Flame-Retardant Chemicals after application of a commercial talcum powder containing 5% boric acid (Mulinos et al. 1953, as cited in Moore 1997; Vignec and Ellis 1954, as cited in IPCS 1998). In rabbits, intact skin acts as a barrier to dermal absorption of boric acid, whereas absorption was much greater through damaged skin (Draize and Kelly 1959). In an in vitro absorption assay, 0.05%, 0.5%, or 5% boric acid solution were applied to human skin, and 1.2%, 0.28%, and 0.7%, respectively, of the boric acid was absorbed (Wester et al. 1998). From those data, flux values of 0.25, 0.58, and 14.58 µg/cm2/hr, and permeability constants (Kp) of 5.0×10−4, 1.2 ×10−4, and 2.9×10−4 cm/hr for the 0.05%, 0.5%, and 5.0% boric acid solutions, respectively, were calculated (Wester et al. 1998). In contrast to the lack of dermal absorption, boric acid is readily absorbed following inhalation and oral exposure. Kent and McCance (1941, as cited in Moore 1997) demonstrated in two female subjects that at least 90% of ingested boric acid is absorbed and excreted in the urine. More recently, Jansen et al. (1984) demonstrated greater than 90% recovery of administered boron in the urine of six male volunteers following ingestion of boric acid. An occupational study of workers involved in packaging and shipping borax (Na2B4O7• 10H2O) showed elevated boron levels in the urine after inhalation exposure (Culver et al. 1994). Metabolism and Distribution Zinc Borate Zinc borate is metabolized to zinc oxide and boric acid prior to being absorbed. Zinc Oxide No relevant human or animal studies were identified that investigated the distribution of zinc following dermal exposure to zinc compounds. No inhalation exposure studies were identified that investigated the distribution of zinc compounds in humans. Cats exposed to zinc oxide fumes (12–61 mg Zn2+/kg-d) for 3 hr had increased zinc levels in the pancreas, liver, and kidneys (Drinker and Drinker 1928, as cited in ATSDR 1994), however, oral absorption through swallowing or grooming cannot be ruled out. There are no data on the metabolism and distribution of zinc oxide following oral exposure. Weigand and Kirchgessner (1992) demonstrated that more zinc is distributed to the kidneys and pancreas than to the liver in rats fed 1.1 mg

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Toxicological Risks of Selected Flame-Retardant Chemicals Zn2+/kg-d (duration unspecified). Administration of zinc acetate to rats (191 mg Zn2+/kg-d in feed for 3 mo) increased zinc levels in the heart, spleen, kidneys, liver, bone, and blood (Llobet et al. 1988). Mice fed 76.9 mg Zn2+/kg-d as zinc sulfate for 1 mo had increased levels of Zn2+ in the kidneys and liver (Schiffer et al. 1991). Newborn, young, and adult mice given a single oral dose of 4.6 mg zinc/kg as zinc chloride generally had the highest level of zinc in the liver, kidneys, lungs, bone, muscle, and carcass 1 d after dosing (He et al. 1991, as cited in ATSDR 1994). Once in the body, zinc induces and binds to metallothionein (a metal binding protein) (Goyer 1996). Retention of zinc bound to metallothionein in tissues provides a source of zinc for essential cell functions even when zinc intake is deficient. In humans and rats, zinc and metallothionein are distributed throughout the body, with a linear relationship between zinc and metallothionein concentrations in the liver (Heilmaier et al. 1987). Boric Acid In humans, boron has been measured in the brain and liver following boric acid poisonings (see review, Moseman 1994). No other data were found on the distribution of boron in humans following exposure to boric acid or borax. In Fischer rats fed 9,000 ppm boron as boric acid (93–96 mg boric acid/kg-d) in the diet, boron was distributed throughout the soft tissues. Accumulation occurred in the bone, but not in the testis or the brain (Ku et al. 1991). Regardless of the compound or route of exposure, once in vivo, boron can form weak complexes with hydroxyl, amino, or thiol groups (Moore 1997). No data were found demonstrating that boron interacts with metallothionein. Excretion Zinc Borate No data were identified that investigated the excretion of zinc borate in humans or animals following any route of exposure. Zinc Oxide No studies were identified that investigated the excretion of zinc in humans or animals following dermal application of any zinc compounds. Elevated levels of zinc were found in the urine of workers exposed to zinc

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Toxicological Risks of Selected Flame-Retardant Chemicals oxide fumes containing unknown concentrations of Zn2+ (Hamdi 1969). No other studies were identified that investigated the excretion of zinc following inhalation of zinc compounds. Following oral exposure to zinc compounds, the primary route of zinc excretion in humans and rats is the feces. Zinc can also be excreted in the urine, saliva, hair, and sweat (ATSDR 1994). Malnutrition or low dietary levels of zinc can promote urinary zinc excretion, possibly as a result of increased levels of tissue breakdown and catabolism (ATSDR 1994). Boric Acid As discussed in the section on Absorption, boron has been detected in the urine after exposure to boric acid via the dermal, inhalation, and oral routes. Following ingestion of boric acid by six male volunteers, greater than 90% of an ingested dose was excreted in the urine within 96 hr (Jansen et al. 1984). HAZARD IDENTIFICATION1 Dermal Exposure Irritation and Sensitization Zinc Borate Zinc borate produced only mild conjunctivitis in albino rabbits in the eye irritation test and is not considered to be an irritant or corrosive (U.S. Borax 1996). Zinc borate was negative in the guinea pig sensitization test (U.S. Borax 1996). Zinc Oxide There are two case studies in the literature that suggest that dermal occupational exposure to zinc oxide might cause or contribute to a skin condition 1   In this section, the subcommittee reviewed toxicity data on zinc borate, including the toxicity assessment prepared by the U.S. Consumer Product Safety Commission (Hatlelid 1999).

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Toxicological Risks of Selected Flame-Retardant Chemicals referred to as “zinc oxide pox” (itchy papular-pustular eruptions that occur in the pubic region, inner surface of the thigh, and axilla and inner surface of the arms). Turner (1921, as cited in ATSDR 1994) found that 14 out of 17 men developed zinc oxide pox at least once during their employment in the bagging or packaging of zinc oxide. However, that effect has been attributed to poor hygiene among the workers, and not necessarily exposure to zinc oxide. In a similar study, Batchelor et al. (1926, as cited in ATSDR 1994) found that only 1 out of a total of 24 workers with occupational exposure to zinc dusts developed zinc oxide pox. Agren (1990, as cited in ATSDR 1994) reported that application of patches containing 25% zinc oxide (equivalent to 2.9 mg Zn2+/m3) to the skin of human volunteers did not produce dermal irritation following 48 hr of exposure. The dermal irritancy of several zinc compounds has been investigated in mice, rabbits, and guinea pigs (Lansdown 1991). Animals were treated topically once a d for 5 consecutive days with zinc oxide (20% suspension in Tween 80), zinc chloride (1% aqueous solution), zinc sulfate (1% aqueous solution), zinc pyrithione (20% suspension), or zinc undecylenate (20% suspension). In open patch tests, zinc chloride was a strong irritant in all three species, and caused the formation of epidermal hyperplasia and ulceration. All other compounds produced less severe erythema than zinc chloride. None of the compounds caused ulceration or scaling over the 5-d test period. Zinc chloride produced severe dermal irritation in rabbits within 3–5 d of application in occlusive patch tests, zinc acetate produced moderate irritation, and little dermal irritation was caused by the other zinc compounds. Histological examination of skin samples from animals treated with zinc chloride or zinc acetate showed evidence of acanthosis, parakeratosis, hyperkeratosis, and inflammatory changes in the epidermis. No studies were identified that investigated the ability of zinc oxide to act as a senzitizer. Boric Acid Dermatitis has been reported following occupational exposure to borax (Birmingham and Key 1963). Boric acid (5 mL, 10% w/v in water) and borax (10 mL, 5% w/v in water) were found to be moderate and mild irritants, respectively, in guinea pigs. Both were mildly irritating to abraded skin after 24–72 hr in rabbits (Roudabush et al. 1965). No studies were identified that investigated the ability of boric acid to act as a skin sensitizer.

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Toxicological Risks of Selected Flame-Retardant Chemicals Systemic Effects Zinc Borate The LD50 in male and female albino rabbits following dermal exposure to zinc borate is estimated to be >10 g/kg (U.S. Borax 1996). Zinc Oxide DuBray (1937, as cited in ATSDR 1994) reported that a worker developed microcytic anemia and had low platelet counts after making zinc chloride solutions. The dose of zinc was not reported. No systemic effects were identified following dermal exposures of animals to zinc oxide. Boric Acid No studies were found on the systemic effects of boric acid following dermal absorption. Other Systemic Effects No studies were found that investigated the immunological, neurological, reproductive, developmental, or carcinogenic effects of zinc borate, zinc oxide, or boric acid following dermal exposure in humans or experimental animals. Inhalation Exposure No data were found on toxic effects of zinc borate following inhalation exposure. Data on the toxic effects of zinc oxide and boric acid following inhalation exposure are discussed below. Systemic Effects Zinc Oxide Although “metal fume fever” has been reported after exposure to zinc oxide, this syndrome is seen following exposure to extremely high concentrations in

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Toxicological Risks of Selected Flame-Retardant Chemicals the occupational setting and is not relevant to exposures from zinc borate-treated upholstered furniture. A number of deaths have been reported in humans following inhalation exposure to airborne mixtures containing very high concentrations of zinc. Ten out of 70 people died within 4 d of exposure to a smoke mixture containing approximately 33,000 mg Zn2+/kg as zinc chloride, in addition to unknown concentrations of hexachloroethane, calcium silicate, and an igniter (Evans 1945, as cited in ATSDR 1994). Milliken et al. (1963, as cited in ATSDR 1994) and Hjortso et al. (1988) reported fatalities after exposure to high, but unknown concentrations of a smoke mixture generated from zinc chloride smoke bombs. Autopsies revealed diffuse micro vascular obliteration, widespread occlusion of the pulmonary arteries, and extensive interstitial and intra-alveolar fibrosis of the lungs (Hjortsu et al. 1988). Although zinc oxide is associated with metal fume fever, and a large amount of research has been carried out in that area, those results are not a focus of this report because exposure to such fumes created by welding are not relevant to our exposure scenario. Nausea has been reported following exposure to high concentrations of zinc oxide in humans (Hammond 1944, as cited in ATSDR 1994; Rohrs 1957, as cited in ATSDR 1994). McCord et al. (1926, as cited in ATSDR 1994) reported that several workers from the galvanized industry had decreased red blood cell counts, but Hamdi (1969) reported that workers exposed to zinc compounds had normal red blood cell counts. Routine blood analysis did not reveal liver disease among 12 workers with 4–21 yr of exposure to zinc oxide (Hamdi 1969). Pulmonary toxicity and reduced survival were reported in female rodents following exposure to zinc oxide/hexachloroethane smoke (119 mg Zn2+/m3 for 1 hr/d, 5 d/wk for up to 20 wk) (Marrs et al. 1988). However, the smoke contained a number of other toxic chemicals (e.g., carbon tetrachloride), therefore, the effects can not be attributed to zinc. A single exposure in rats and rabbits to 88–482 mg zinc/m3 as zinc oxide resulted in pulmonary congestion and leukocytic infiltration (Drinker and Drinker 1928; as cited in ATSDR 1994). Amdur et al. (1982) demonstrated a decreased lung compliance following exposure of guinea pigs to 0.73 mg zinc/m3 as zinc oxide for 1 hr. Lam et al. (1982) did not see an effect on ventilation, but did see an effect on functional residual capacity after exposure of guinea pigs to 6.3 mg zinc/m3 as zinc oxide for 3 hr. Deficits in lung function were seen in guinea pigs exposed to zinc oxide dust (3.7–5.6 me zinc/m3) 3 hr/d for up to 6 d (Lam et al. 1985, 1988). No effects were seen at a concentration of 2.2 mg zinc/m3 as zinc oxide (Lam et al. 1988). However, guinea pigs appear to be more sensitive to the pulmonary effects of zinc oxide than humans because of differences in lung structure (Lam et al. 1982).

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Toxicological Risks of Selected Flame-Retardant Chemicals Boric Acid In the occupational setting, toxic effects following exposure to boron are generally acute, and include nosebleed, nasal irritation, sore throat, cough, and shortness of breath (IPCS 1998). Garabrant et al. (1984) found an increase in reports of eye irritation, dry mouth, nose or throat irritation, and productive cough in workers in a borax mining and refining plant. Chronic bronchitis, without any abnormal regions on a chest X-ray or impairment of pulmonary function, was also found in the borax plant (Garabrant et al. 1985). In a prospective study of workers exposed to sodium borate dust in a mine and processing plant, Wegman et al. (1994) found increased nasal, eye, and throat irritation, cough, and breathlessness. No long-term effects were found in that study. Exposure to boric acid 6 hr/d, 5 d/wk had no effect on body weight gain, hematology, blood chemistry, urinalysis, or microscopic analysis in rats (77 mg/m3 for 24 wk; 175 mg/m3 for 12 wk, or 470 mg/m3 for 20 wk) or dogs (57 mg/m3 for 23 wk) (Wilding et al. 1959, as cited in ATSDR 1992). Immunological Effects No studies were identified that investigated immunological effects of boric acid following inhalation exposure. Data from three case reports suggest that inhalation exposure to high concentrations of zinc-containing compounds stimulates changes in immune parameters. Farrell (1987) reported that a worker developed hives and angioedema (suggestive of an immediate or delayed IgE response) following exposure to a low dose of zinc oxide fumes. The symptoms reappeared in a challenge test, suggesting a sensitization to zinc compounds. A correlation between exposure to zinc oxide and the proportion of activated helper-, inducer-, suppressor-, and killer-T-cells was observed among 14 welders approximately 20 hr after exposure to zinc oxide (77–153 mg Zn2+/m3) (Blanc et al. 1991, as cited in ATSDR 1994). Ameille et al. (1992) reported elevated levels of lymphocytes in the bronchoalveolar lavage fluid of a smelter worker exposed to unknown concentrations of zinc fumes. Cytokine responses have been observed in bronchoalveolar lavage after inhalation of zinc oxide fumes from welding (Blanc et al. 1993; Kuschner et al. 1995, 1997). Marrs et al. (1988) did not observe abnormalities in the lymph nodes, thymus, or spleen tissue of female rats, mice, or guinea pigs killed 18 mo after a 20-wk exposure to zinc oxide/hexachloroethane smoke at concentrations as high as 119.3 or 121.7 mg Zn2+/m3 for 1 hr/d, 5 d/wk.

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Toxicological Risks of Selected Flame-Retardant Chemicals 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 zinc borate, that 1/4th of the upper torso is in contact with the upholstery, and that clothing presents no barrier. Zinc borate is considered to be ionic, and is essentially not absorbed through the skin. However, to be conservative, the subcommittee assumed that ionized zinc borate 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 zinc borate (2 mg/cm2), and Equation 1 in Chapter 3, the subcommittee calculated a dermal exposure level of 6.3×10−3 mg/kg-d. The oral RfD for zinc borate (0.6 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 1.0×10−2. Thus it was concluded that zinc borate used as a flame retardant in upholstery fabric is not likely to pose a noncancer risk by the dermal route. Inhalation Exposure Particulates The assessment of the noncancer risk by the inhalation route of exposure is 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 low air-change rate (0.25/hr) and with a relatively large amount of fabric upholstery treated with zinc borate (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 zinc borate 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 zinc borate present in the air. The highest expected application rate for zinc borate is about 2 mg/cm2. The estimated release rate for zinc borate is

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Toxicological Risks of Selected Flame-Retardant Chemicals 2.3×10−7/d. Using those values, the estimated time-averaged exposure concentration for zinc borate is 0.19 µg/m3. Although lack of sufficient data precludes deriving an inhalation RfC for zinc borate, the oral RfD (0.6 mg zinc borate/kg-d; see Oral RfD in Quantitative Toxicity section), which represents a conservative estimate, was used to estimate an RfC of 2.1 mg/m3 (see Chapter 4 for the rationale). Division of the exposure concentration (0.19 µg/m3) by the estimated RfC (2.1 mg/m3) results in a hazard index of 9.1×10−5. Therefore, the subcommittee concluded that, under the worst-case exposure scenario, exposure to zinc borate particles from its use as an upholstery fabric flame retardant is not likely to pose a noncancer risk. Vapor In addition to the possibility of release of zinc borate in particles worn from upholstery fabric, the subcommittee considered the possibility of its release by evaporation. However, because of zinc borate’s negligible vapor pressure at ambient temperatures, the subcommittee concluded that exposure to zinc borate 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. The exposure assumes a child is exposed to zinc borate through sucking on 50 cm2 of fabric, backcoated with zinc borate, daily for two yr, one hr/d. The highest application rate for zinc borate is 2 mg/m2. A fractional rate (per unit time) of zinc borate 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 in Equation 15 in Chapter 3, the average oral dose rate was estimated to be 0.00017 mg/kg-d. Division of that exposure estimate (0.00017 mg/kg-d) by the oral RfD (0.6 mg/kg-d; see Oral RfD in Quantitative Toxicity Assessment Section) results in a hazard index of 2.8×10−4. Therefore, under the worst-case exposure assumptions, zinc borate, used as a flame retardant in furniture-upholstery fabric, is not likely to pose a noncancer risk by the oral route of exposure.

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Toxicological Risks of Selected Flame-Retardant Chemicals Cancer There are inadequate data to characterize the carcinogenic risk from exposure to zinc borate, zinc oxide, or boric acid from any route of exposure. RECOMMENDATIONS FROM OTHER ORGANIZATIONS The U.S. Environmental Protection Agency (EPA), as detailed in the Integrated Risk Information System (IRIS), has established an oral RfD for boron of 0.09 mg/kg-d (EPA 1999). The risk assessment for boron has not been updated since 1989. However, that RfD is currently under review and a revised RfD is expected in the yr 2000 (Fed. Regist. 63 (December 10, 1998):68353–68364). The International Programme on Chemical Safety (IPCS) has an Environmental Health Criteria document (IPCS 1998) on boron in which a tolerable intake for boron is set at 0.4 mg boron/kg-d based on recent reproductive and developmental data. The Agency for Toxic Substances and Disease Registry (ATSDR) has published toxicological profiles for zinc and boron. An oral minimal risk level (MRL) of 0.3 mg Zn/kg-d for zinc was based on hematological effects (ATSDR 1994). ATSDR lists an oral MRL for boron of 0.01 mg boron/kg-d based on developmental effects (ATSDR 1992). The National Research Council (NRC) has established a recommended dietary allowance (RDA) for zinc of 12–15 mg/d (0.17–0.21 mg/kg-d of zinc for a 70-kg person (NRC 1980). The Occupational Safety and Health Administration (OSHA) and the American Conference of Government Industrial Hygienists (ACGIH) considered the toxicity from zinc borate and its components in the workplace to be due to “Particulate Not Otherwise Classified” or “Nuisance Dust.” Therefore, the OSHA permissible exposure level is 15 mg/m3 for total dust and 5 mg/m3 for respirable dust, and the ACGIH Threshold Limit Value for zinc oxide dust is 10 mg/m3 (ACGIH 1999). DATA GAPS AND RESEARCH NEEDS There are little toxicity data available for zinc borate. Once in the body, zinc borate readily breaks down to zinc oxide and boric acid. There are no chronic studies investigating the carcinogenicity of zinc oxide and boric acid. There are

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Toxicological Risks of Selected Flame-Retardant Chemicals no studies that measured exposure levels from the use of zinc borate as a flame retardant in upholstery furniture fabric. However, there are extensive databases on the toxicity of zinc oxide and boric acid, and the hazard indices for zinc borate, based on those data, are less than one for all three routes of exposure, using the subcommittee’s conservative assumptions. Therefore, the subcommittee concluded that no further research is needed to assess the health risks from the use of zinc borate as a flame retardant. REFERENCES ACGIH (American Conference of Government Industrial Hygienists). 1999. Threshold Limit Values and Biological Exposure Indices. Cincinnati, OH: American Conference of Government Industrial Hygienists, Inc. Agren, M.S. 1990. Percutaneous absorption of zinc from zinc oxide applied topically to intact skin in man. Dermatologica 180:36–39. Agren, M.S. 1991. Influence of two vehicles for zinc oxide on zinc absorption through intact skin and wounds. Acta Derm. Venereol. 71(2): 153–156. Agren, M.S., M.Krusell, and L.Franzen. 1991. Release and absorption of zinc from zinc oxide and zinc sulfate in open wounds. Acta Derm. Venereol. 71(4):330–333. Allen, B.C., P.L.Strong, C.J.Price, S.A.Hubbard, and G.P.Daston. 1996. Benchmark dose analysis of developmental toxicity in rats exposed to boric acid. Fundam. Appl. Toxicol. 32(2): 194–204. Amdur, M.O., J.F.McCarthy, and M.W.Gill. 1982. Respiratory response of guinea pigs to zinc oxide fume. Am. Ind. Hyg. Assoc. J. 43(12):887–889. Ameille, J., J.M.Brechot, P.Brochard, F.Capron, and M.F.Dore. 1992. Occupational hypersensitivity pneumonitis in a smelter exposed to zinc fumes. Chest 101(3):862–863. ATSDR (Agency for Toxic Substances and Disease Registry). 1992. Toxicological Profile for Boron. U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA. 86 pp. ATSDR (Agency for Toxic Substances and Disease Registry). 1994. Toxicological Profile for Zinc (Update). U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, Atlanta, GA. TP-93/15. 230pp. Bakke, J.P. 1991. Evaluation of the potential of boric acid to induce unscheduled DNA synthesis in the in vitro hepatocyte DNA repair assay using the male F-344 Rat. SRI International (Study No. 2389-V500–91 (EPA MRID 420389–03). Batchelor, R.P., J.W.Fehnel, R.M.Thompson, et al. 1926. A clinical and laboratory investigation of the effect of metallic zinc, of zinc oxide, and of zinc sulphide upon the health of workmen. J. Ind. Hyg. 8:322–363. Bauchinger, M., E.Schmid, H.J.Einbrodt, and J.Dresp. 1976. Chromosome aberrations in lymphocytes after occupational exposure to lead and cadmium. Mutat. Res. 40(1):57–62. Birmingham, D.J., and M.M.Key. 1963. Preliminary survey: U.S. Borax plant, Califor-

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