Document VJd5kyknBwEJ4zME7agYK11Go

TO: T. G. Grumbles Interoffice Communication FROM: DATE: SUBJ M. M. Goodreau April 13, 1989 CATAPAL ALUMINA VIS1A Regulations under the OSHA Hazard Communication Standard and SARA Section 313 require you to have precise information on the definition, nomenclature, and CAS number of your product to determine its regulatory status. Within Vista the terms alumina, aluminum oxide, aluminum hydroxide, etc. are used for Vista's CATAPAL Alumina's. This wide variation in nomenclature use has caused some confusion when determining the regulatory status of our alumina's. We have researched this issue to clarify the regulatory status of CATAPAL Alumina's. The following classifications and resultant regulatory requirements have been developed. CATAPAL G and GST (calcined and ground calcined alumina) and Whiskers are believed to most accurately be defined as aluminum oxide's with the CAS number 1344-28-1. Table I (attached) shows other pseudonyms listed in the TSCA inventory for this material. All other LCCP produced CATAPAL Alumina's are believed to be most accurately be defined as Boehmite with the resultant CAS number 1318-23-6. CATAPAL G and GST aluminas and whiskers, defined as aluminum oxide, CAS No. 1344-28-1, are listed both by name and CAS number on the SARA Section 313 list of Toxic Chemicals. Emissions of aluminum oxide must be reported annually to the EPA. In addition, suppliers of products containing 313 chemicals must annually inform their customers of the presence of 313 chemicals in a product. Aluminum oxide (Catapal G and GST aluminas and whiskers), CAS No. 1344-28-1, is listed both by name and CAS number in the OSHA ZTables and the ACGIH TLV's with a PEL/TWA of 10 mg/M total dust. Because it is listed in these reference sources it is a chemical on OSHA's "floor list" of hazardous chemicals, subject to all provisions of OSHA's Hazard Communication Standard (HCS). The products described by the CAS No. 1318-23-6 are not subject to SARA Section 313. As to whether they are subject to the OSHA HCS depends on Vista's independent hazard evaluation. The other "alumina's" listed in Table I are not listed by name or CAS number in OSHA's Z-Tables or ACGIH TLV's. They are, however, considered to be "nuisance particulates" which are listed by both reference sources with a PEL/TWA of 10 mg/ra3 total dust. OSHA has recently stated that "nuisance particulates" are hazardous as defined by the OSHA HCS as a result of their being listed in these reference sources. OSHA continued to say that you may perform an independent VVV 000010505 Grumbles Memo April 13, 1989 Page 2 hazard, evaluation and may determine the nuisance particulate in question to be non-hazardous. Until the independent evaluation is completed, the material is assumed to be hazardous, and subject to all provisions of OSHA's HCS. After much discussion and a review of available toxicology data, we have determined that all CATAPAL alumina products, excluding CATAPAL G, GST, and Whiskers, are nonhazardous as defined by the OSHA hazard communication standard. If I can provide further clarification on this subject, please contact me. M. M. Goodreau dlj .402 cc: J. R. Drurawright, D. L. Cohen, W. L. McClain, G. Hoenes, W. S. Tuzinkiewicz M. G. Hayes, K. L. Fogg-LCCP, J. T. Fenton-Ponca City 000010506 Grumbles Memo April 13, 1989 Page 3 TABLE I: PSEUDONYMS AND CAS NUMBERS 1344-28-1 1318-23-6 24623-77-6 inventory) 21645-51-2 AI2O3 alumina aluminum oxide (as listed in the TSCA inventory) alumina, calcined - aluminum oxide AIHO2 or Al(OH)0 or AI2 O3 H2O Boehmite (as listed in the TSCA inventory) Ps eudob 0 ehmite aluminum hydroxide oxide (as listed in the TSCA A1(0H)0 or AIHO2 AIH3O3 or A1203 3H20 or Al(OH)3OH)3 aluminum hydroxide (as listed in the TSCA inventory) alumina trihydrate aluminum trihydroxide aluminum hydrate hydrated alumina hydrated aluminum oxide VVtf 000010507 VISTA MATERIAL SAFETY DATA SHEET Vista Chemical Company Houston, TX 77224 1. PRODUCT IDENTIFICATION MANUFACTURER'S NAME Vista Chemical Company ADDRESS TRADE NAME SYNONYMS P.O. Box rzi, Westlake, la /Ubti VISTA CATAPAL^AIumina Boehmite, Al203h2o CAS NUMBER REGULAR TELEPHONE NO. (318)494-5403 EMERGENCY TELEPHONE NO. (318)494-5142 2. HAZARDOUS INGREDIENTS MATERIAL OR COMPONENT Aluminum Hydroxide Oxide % 75 HAZARD DATA nuisaii^a Oust niiiaialiOiil ! Imoi'u 3. PHYSICAL DATA BOILING POINT (F) VAPOR PRESSURE (mm Hg.) SOLUBILITY IN WATER APPEARANCE AND ODOR Not applicable Not applicable Nil SPECIFIC GRAVfTY (H20 =1) MELTING POINT VAPOR DENSITY White powder, odorless. V* Not applicable Not applicable Not applicable 4. FIRE AND EXPLOSION DATA FLASH POINT Not applicable (TEST METHOD) AUTOIGNITION TEMPERATURE FLAMMABLE LIMITS IN AIR. % BY VOL LOWER Not applicable UPPER | EXTINGUISHING MEDIA Non-flammable material. Not applicable Not applicable SPECIAL FIRE FIGHTING PROCEDURES Non-flammable material. VVV OOOmncnn 3 UNUSUAL FIRE Not applicable. This is an inert material and will not produce a dust explosion AND EXPLOSION HAZARD 5. HEALTH HAZARD INFORMATION FIRST AID Flush with large amounts of water for at least 15 minutes. If irritation occurs, seek EYES: medical aid. SKIN* Plush with water. INHALATION* ^ exposed to excessive amounts, remove to fresh air. INGESTION: Seek medical advice. NATURE OF HAZARD EYES: May cause physical irritation if exposed to large amounts of dust. SKIN: No hazard under normal circumstance. INHALATION* May cause physical irritation to upper respiratory tract. This material is a iNnALAllUN: nujsance dust and as such does not produce significant organic disease or toxic effect with reasonable exposures. INGESTION* No hazard under normal circumstances. EFFECTS OF OVEREXPOSURE: ACUTE OVEREXPOSURE: PhYsical irritation. CHRONIC OVEREXPOSURE: Physical irritation. No known long-term toxic effects. THRESHOLD LIMIT VALUE (TLV) Vista recommends this material be treated as a nuisance dust. 1985-86 ACGIH TLV: 10 mg/m3 of total dust and 5 mg/m3 respirable dust. OSHA PEL: 15 mg/m3 of total dust and 5 mg/m3 respirable dust. TOXICITY DATA SKIN CONTACT: Rabbit skin LD0: 4 g/Kg Rabbit skin irritation index: 0.2 (max. score possible is 8.0) EYE CONTACT: Rabbit eye irritation index: 6 (max. score possible is 110) INHALATION: Rats survived exposure to a concentration of 83 mg/l for one hour. INGESTION: Acute oral LD^ in rats: 20 g/kg ooooi SPECIAL PRECAUTIONS: AV0ID inhalation 6. REACTIVITY DATA CONDITIONS CONTRIBUTING TO INSTABILITY Stable and non-volatile material. INCOMPATIBILITY Not applicable. HAZARDOUS DECOMPOSITION PRODUCTS Not applicable. CONDITIONS CONTRIBUTING TO HAZARDOUS POLYMERIZATION Not applicable. 7. SPILL OR LEAK PROCEDURES STEPS TO BE TAKEN IF MATERIAL IS RELEASED OR SPILLED Material should be picked up mechanically and placed in drums, bins, or other appropriate containers. NEUTRALIZING CHEMICALS Not applicable. WASTE DISPOSAL METHOD May be disposed of in a landfill according to local, state and federal regulations. 8. SPECIAL PROTECTION INFORMATION VENTILATION REQUIREMENTS Mechanical ventilation should be used to control dust levels below the PEL and TLV. SPECIFIC PERSONAL PROTECTIVE EQUIPMENT RESPIRATORY (SPECIFY IN DETAIL): NIOSH approved air-purifying dust respirator. EYE: Chemical goggles. GLOVES: Not needed. OTHER CLOTHING AND EQUIPMENT: Not needed. ooooio*10 9. SPECIAL PRECAUTIONS HAZARD CLASSIFICATION INFORMATION IMO HAZARD CLASS AND NUMBER No hazard classiHcatier, US DOT HAZARD CLASS Me hezerd UN NUMBER Not applicable US DOT IDENTIFICATION NUMBER Not applicable TRANSPORTATION AND STORAGE USUAL SHIPPING CONTAINERS Railroad Hopper Cars Tank Trucks Bags ELECTROSTATIC ACCUMULATION HAZARD None STORAGE/TRANSPORT PRESSURE Ambient STORAGE TRANSPORT TEMPERATURE Ambient LOADING/UNLOADING TEMPERATURE Ambient VISCOSITY AT LOADING/ UNLOADING TEMPERATURE t HANDLING AND STORAGE MATERIALS AND COATINGS SUITABLE UNSUITABLE Carbon Steel Mild Steel Aluminum Abrasion in handling systems may occur. THE ABOVE DATA IS BASED ON TESTS AND EXPERIENCE WHICH VISTA BELIEVES RELIABLE AND ARE SUPPLIED FOR INFORMATIONAL PURPOSES ONLY. VISTA DISCLAIMS ANY LIABILITY FOR DAMAGE OR INJURY WHICH RESULTS FROM THE USE OF THE ABOVE DATA AND NOTHING CONTAINED THEREIN SHALL CONSTITUTE A GUARANTEE, WARRANTY (INCLUDING WARRANTY OF MERCHANTABILITY) OR REPRESENTATION (INCLUDING FREEDOM FROM PATENT LIABIL ITY) BY VISTA WITH RESPECT TO THE DATA, THE PRODUCT DESCRIBED, OR THEIR USE FOR ANY SPECIFIC PURPOSE, EVEN IF THAT PURPOSE IS KNOWN TO VISTA. Revised: May 1986 LC13 Alumina-related Pulmonary Disease Bertram D. Dinman, MD, ScD VVV 0000X0511 A review of experimental studies suggests that the catalyticaily active low temperature transitional forms of alumina produces irreversible fibronodular change only when admin istered by intratracheal Insufflation. Other aluminas not catalytically active but also broadly identified as "gamma" for different reasons also appear capable of inducing pulmonary fibrosis in the same model. Under conditions of human expo sure, occupational exposure to a broad range of aluminas indicates--at most--minimal pulmonary nodular response. within this frame of reference, this report will attempt to place in perspective studies using both experimental models and human encounters with this group of alu minum, oxygen, and hydrogen-containing compounds, the aluminas. Experimental Studies of Alumina's Actions in the Lungs ssessment of biomedical studies of the toxicity of Aalumina in the lung is complicated by inconsisten cies in the nomenclature used to describe chemical and physical variants of this compound. The biologic litera ture can be evaluated only to the extent that investi gators have clearly identified the individual alumina species studied. Only with careful physical-chemical de lineation of these physical-chemical entities is it possible to place experimental and human data in perspective so as to understand the biologic and health implications of exposure to aluminas. To complicate the situation further, various biologic On the basis of an examination of those reports which provide sufficient chemical and physical specifications. It is possible to identify aluminas previously studied in terms of present day knowledge. These specific aluminas are summarized in Table 1. Gardner et al1 reported that inhalation of a gelatinous alumina (designated 7-HX1010), presently known to be gelatinous boehmite, apparently did not produce dele terious pulmonary alterations when administered to guinea pigs in doses of approximately 40 to 120 mg/m3. Among its other properties, gelatinous boehmite usually possesses an extremely high surface area (250 to 500 models have been developed as surrogates for the study of human interactions with chemical agents. With the evolution of such model systems, a broader understand ing of their utility and limitations is revealed. Although biologic mechanisms of action may be demonstrated by such experimental systems, their applicability to the human condition is frequently limited, eg, because of high dose regimens and nonphysiologic portals of entry or administration. Such reservations have been exten sively discussed in connection with studies of carcino genesis; similar reservations are equally applicable to investigations of pulmonary response to dusts, or vapor, or gases. But within these constraints, and in conjunc tion with clinical investigations, such models can assist in elucidation of human responsivity and risk. Thus, Gardner administered by inhalation at doses of 21 to |/33 mg/m3 a second alumina which he identified as C- 730. His description of the mode of preparation indicates that this alumina was gibbsite; heated at atmospheric pressure, this aluminum trihydroxide dehydrates mainly to the x transitional form, a catalytically active alumina. Once more, no pathologic alterations ensued following inhalation exposure. The benign outcomes of the studies of Gardner et al1 stand in stark contradiction to the findings of King and associates3: in their laboratory, this same HX1010 ge latinous boehmite (referred to as 7-AIOOH) produced extensive nodular and diffuse confluent fibrosis. It is . important to note that King et al3 administered this alumina via intratracheal insufflation. Because of'tKls"major^3iffereRce-Ifr response, further efforts in King's laboratory by Stacy et al4 culminated From the Department of Industrial Environmental Health Sciences, Graduate School of Public Health, University of Pittsburgh, Pitts burgh, PA 16261 (address correspondence to Dr Dinman),. 0096-1736/88/3004-0388808.00/0 Copyright $ by American Occupational Medical Association in more extensive and systematic intratracheal insuffla tion studies of several aluminas (Table 1). Stacy and co-workers,4 using the same gelatinous boehmite (7A100H, HX1010) replicated King's results, ie, moder ately severe pulmonary fibronodular change. 328 Alumina-related Pulmonary Disease/Dinman Investigator Gardner et at' King et aP Stacy et al4 Klosterkotter8 TABLE 1 Review of Experimental Data with Contemporary Evaluation of Alumina Species Agsnt Investigator Identity Designation <17) Crystalline Packing Arrangement Route of Administration Particle Size, *tm Surface Area, m*/g Catalytic Activity C-730, acti vated HX1010 7AIOOH HX1010 7-AIOOH HX1010 7-AI2O9 HX1010 at 850C 7-AIOOH Cera hy drate* ci'AljOj HX1010 at 1,200C T-AlaOs x transi tional Gelatinous boeh mite Gelatinous boeh mite Gelatinous boeh mite 1j transi tionaJ Boehmite a-AI*03 (corun dum) 7 transi tional 7-AI*03 7 transi tional 7 y' y* y* y y a y y Inhalation Inhalation ? 0.02 250-? 250-350 + Intratracheal insuffla tion Intratracheal insuffla-' tion Intratracheal insuffla tion Intratracheal insuffla tion Intratracheal insuffla tion 0.02-0.04 250-350 0.02-0.04 250-350 0.02-0.04 60-? 3 0.6 0.1-0.8* 3 Intratracheal insuffla tion Inhalation 0.005-0.04 0.005-0.04 95-105 95-105 + + + ' This alumina is only minimally crystalline, t System of fibrosis grading of King et al.3 i Estimated by review of electron micrographs of Stacy et al.4 Dose, mg Response 21-33/m3 35-105/m3 No harmful effects No harmful effects 100 +3 to +5/5 fi- brosist 50 +3/5 fibrosisf 50 +5/5 fibrosisf 50 0 fibrosisf 50 +1/5 fibrosisf 35 +3/5f 3300/m3 Alveolar pro teinosis! VVV 000010512 Next, this gelatinous boehmite was heated to 850oC; the dehydration formed what Stacy referred to as 7AlsOs. However, present knowledge0 indicates that the product of dehydration at this temperature results largely in the formation of the 77 transitional form, a catalytically active aluminum oxide (cf "Technical Note"). Nevertheless, intratracheal insufflation of what was probably the 17 transitional AlOd resulted in severe pulmonary fibronodular alteration. The third alumina studied by Stacy was the thermal dehydration product of the same gelatinous boehmite HX1010 heated to 1,200C which led to the formation of a-aluminum oxide (Fig. 1) (see also Fig. 2) or corun dum. These crystals were then ground to a smaller particle size, which appeared to range from 0.1 to 0.8 /im. When administered intratracheally, cv-A1803 pro voked a minimal but consistent degree of fibronodular lung pathology. The fourth alumina investigated was the highly crys talline, large particle size (ie, 3.0 71m mean diameter) 7-AIOOH boehmite (referred to as Cera hydrate"). This catalytically inactive alumina given intratracheally at similar doses as the other aluminas was inert in the lungs. These data of the London-Post Graduate School clearly indicate (cf Table 1), within the context of the ^ intratracheal insufflation model, that (1) exposure to f\ the catalytically active ij transitional form results in / 1 severe fibronodular alteration; (2) exposure to certain ! catalytically inactive aluminas (viz. a-Al803 and gelat- * inous boehmite) produces a lesser but broader range of fibronodular change; and (3) in view of the broad range of reactivity to variously described 7-aluminas (ie, zero response with 7-AIOOH boehmite, extending to severe alterations with ij transitional form), and (4) in view of a minimal but consistent response to a fine a-alumina, (5) it is inconsistent to associate 7-aluminas with pul monary hazard. (6) This position is reinforced by the probability that the London School never exposed their animals to any specific 7-aluminum oxide (ie, 7-tranaitional). Since the London investigators' experiments3,4 were based upon intratracheal insufflation dosings, Klosterkotter6 attempted to study the effect of inhala tion of what was believed to be the most biologically active of these aluminas, a relatively well-defined 7 transitional form AlsOa. However, because his dosage was so extremely large, ie, 33 g/m3 for each of 285 days, this massive overloading produced what would presently be considered as alveolar proteinosis, a nonspecific re sponse to large pulmonary dust loadings. Accordingly, the implications of his experiments for only the most excessive human exposures to 7 transitional AlaOa should still be considered as questionable. Regarding these experiments, it is indeed ironic that, of the multiple forma of aluminas investigated, a specific fibronodular response apparently has never been pro duced by the only one specific 7-alumina, ie, the 7 transitional form. In more precise terms, a fibronodular response can only be said to have resulted from intra- Joumal of Occupational Medicine/Volume 30 No. 4/April 1988 329 ^Transitional Ai.O, ihxiOIO heaieo to 650X1 1----------3------- 2 I----Q- Gelalinous Soenmite 1 TAIOOH. MXlOlOi l-G-t a AI.O, (ConjnOumi iHXlOlQ healed to 1200C) / yAlOOH. Soefl/nite \Cera nyOrate 1 J__J___ * iiii 10 Surface Area. M Vi 100 VVV 000010513 Fig. 1 Correlation of Surface Area of Aluminas with Pulmonary Fibrosis Graded According to Stacy et al.` tracheal insufflation of (1) catalytically active, low tem perature range transitional, and/or (2) relatively high surface area aluminas. In order to clarify the biomedical literature, we would propose that the reference to yaluminas be discontinued, and that this intratracheal model's effect be specifically associated with these two alumina species and their properties. More recent inhalation studies of aluminum oxide reported the production of nonspecific polymorphonu clear response characteristic of a wide variety of cyto toxic and nonpathogenic particulates. By contrast, A10O3 did not provoke increased alveolar macrophage re sponse,7 suggesting only minimal potentials for chemotaxic or fibronectin release and injury associated with such events. Although more studies of the alumina's effect upon alveolar macrophages are indicated, pres ently available data do suggest a relatively efficient elimination from the lunga and a low degree--if any-- of fibrogenicity. Other investigations of corundum (aA1803) indicated an inability to evoke lung tissue acid phosphatase, which has been associated with develop ment of fibrogenic response.9 Occupational Exposure to Aluminas Unfortunately, most reports of occupational exposure to aluminas unmixed with other dusts have not provided specifics sufficient to adequately define the qualitative nature of worker exposures. Much of this stems from the failure of biomedical investigators to appreciate these multiple variations in alumina's physical and chemical forms. Moreover, workplace characterization is complicated by the reality that production and use of specific aluminas varies in response to marked demands and/or technologic changes at various times and places. Furthermore, in the production of aluminas, relatively ^ few employees are exposed to alumina dust. Such dust exposures that do occur are found in the vicinity of kilns at grinding, screening, transport, and packing opera tions. Given these facts, it is understandably difficult to characterize precisely the quantitative as well as qual itative nature of employee exposures in the course of alumina production. Studies of alumina refineries in which one would encounter aluminas unmixed with other dusts are rel atively uncommon; however, a recent study of alumina refinery workers reported by Townsend et al10 repre sents such exposures. This alumina chemical refinery employing 1,109 potentially exposed workers has been engaged in the production of various aluminas, predom inantly the chemical grades. Production data available showed that since 1958 these workers have processed 244,500 tons of the low temperature transitional alu minas (viz, tj, y, x) representing 2.9% of the total aluminas produced since that time. Accordingly, expo sure to the intratracheally bioreactive low temperature range transitional alumina species has been occurred here on an intermittent basis from 1952 until 1982. A search for pulmonary fibrosis and pneumoconiosis in this population yielded essentially negative results11; the major change reported was a slight but significant decrement in ventilatory function among nonsmoking workers exposed to excessive total dust levels. The observed changes were consistent with a minor degree of nonspecific chronic industrial bronchitis associated with excessive, protracted nuisance dust exposure, (ie, 100 mg-years for more than 20 years). Other reports of occupational exposure to aluminas unmixed with other dusts occur in connection with pottery production. In that industry, a-aluminum oxide is used to support green, unfired pottery and flatware.19 330 Alumina-related Pulmonary Disease/Dinman Because of the ease with which this stable form of corundum a-Al0Oa becomes airborne, exposure of work ers in this industry has been the subject of multiple epidemiologic and clinical investigations in the United Kingdom.13'14 None of these investigators have found evidence of pneumoconiosis or chronic respiratory dis ease. Reports of exposure to an otherwise uncharacterized alumina which is probably unmixed with other, dusts have been provided by Szczekocki and co-workers.15 Although their interests lay in whole body absorption and excretion of aluminum, they briefly note in their clinical evaluations that 49 workers engaged in the reloading of aluminum oxide showed no roentgenographic evidence of pneumoconiosis. Alumina exposures in aluminum smelters are mixed, involving such other pulmonary irritants as hydrogen fluoride and inorganic fluoride particulates, as well as low levels of sulfur dioxide. The difficulty inherent in the study of mixed exposures among aluminum smelter workers has been commented upon by Saia et al,ia who reported pulmonary opacities of a minor degree in castiron foundries where mixed exposures similarly oc curred.17 Similarly, small irregular opacities of category 1/0--or at most, l/l--have been found among workers exposed to coal dust18 and man-made mineral fibers.19 Putting aside the confounding variables involved in mixed dust exposures present in aluminum reduction, changes in the character of smelting type aluminas which have evolved since the 1950s are of interest. With the introduction of flash and fluid phase calciners in the alumina refining industry, lower temperatures and faster flow-throughs are achieved. Thus, by calcining aluminas at a lower temperature, more of the higher temperature transitional forms (cf Technical Note and Fig. 2) and less or-aluminas are produced; in addition, among the high temperature transitional aluminas (eg, y, k, d, and o'), surface areas larger than that associated with a-alumina are formed (cf Technical Note and Fig. 3). This is advantageous, as these high temperature transitional aluminas used as smelting feedstock make more effective adsorptive media when they are used to scrub airborne smelter effluents. Thus, as economics drove this rapid, lower temperature calcination throughout the industry, increasing percentages of transitional y, k, 8, and 6 aluminas have come to be the major component of the aluminas used in aluminum smelting. At present, smelting grade aluminas--which comprise 90% of the world's alumina production--may contain as little as 1% of or-aluminum oxide, although more usually 80% to 90% of smelting aluminum will consist of the high-temperature transitional forms k, 6, and 6. Under such operating conditions, which have gradu ally applied since midcentury, evaluation of lung changes in aluminum smelter operators since that time could shed light upon the pulmonary reactivity of the y transitional-laden smelting grade aluminas. At present, population studies of smelter employees indicate either minimal 18 or absent fibronodular disease30-81 nor excess mortality23 associated with pneumoconiosis. In most of these studies, smelter workers have predominantly been exposed to the high temperature range transitional aluminum oxide aluminas since the late 1960s. In none of the foregoing aluminum reduction operations did cell room attendants evidence changes consistent with al terations seen by King et al3 or Stacy and co-workers4 with intratracheal insufflation of the low temperature (77) transitional alumina. In contrast to population stud ies, individual case reports from smelters note lung fibrosis23 or fibronodular alteration.24 Ultimately, the strength of these associations must be borne by the weight of available evidence. Discussion The biomedical literature dealing with the aluminas suffers from imprecisions regarding the nature of the agent component of the host-agent interaction. Because they most clearly identify which aluminas were inves; tigated. the London intratracheal insufflation reports are valuable. In the case of the Stacy group's reports,4 1 a gradation of response to similar doses of several I different aluminas is demonstrated, despite the dispu tatious route of administration. Had all these dosings led to severe or uniform response to the aluminas, a more plausible case for total disregard of these data might be appropriate. That there was a broad range of response to these agents suggests reason for serious consideration of their findings. A re-examination of the King group's3 data therefore is useful to the extent one understands the limitations of their model's implications for human exposure conditions. We suggest that an association between pulmonary flbrogenicity, surface area, and catalytic activity (Table I) is apparent upon consideration of the characteristics of these aluminas. Examination of King and Stacy's range of pulmonary response as related to surface area (Fig. 1) suggests an association between these two variables among the noncatalytic aluminas. We would propose that increased thermodynamic instability and enhanced bioreactivity of these compounds occur as surface area increases (cf Technical Note). (Of interest in this connection is Timbrell's recent report,36 which correlates surface area with the pulmonary bioreactiv ity of various mineral forms of asbestos.) Regarding the catalytic activity of the low tempera ture transitional forms of alumina (ie, 77, x, y), enhance ment of pulmonary bioreactivity resulting from their thermodynamically active catalytic character is also suggested by Fig. 1. It would be reasonable to suggest that this property is responsible for that increment of lung damage beyond that due to the surface area factor. Because of gaps in knowledge at the time Stacy and co-workers4 performed their experiments, they could not be aware that they probably had not dosed with the specific gamma transitional alumina form. Aside from inadvertent confusion in the literature, this is not a serious shortcoming from the biomechanistic viewpoint, since the low temperature transitional alumina 77 pos sesses catalytic and surface area characteristics com mon to the other low temperature transitional forms y and x> Journal of Occupational Medicine/Volume 30 No. 4/April 1988 VVV 000010514 331 All of the foregoing reports of King, Stacy and asso ciates must be considered within limitations imposed by intratracheal insufflation models; the massive dosing and overwhelming of defense mechanisms represents a "forcing" model reminiscent of megadose carcinogenesis experiments. A parallel is exemplified by the large dose animal studies with halogenated aliphatics: although alternate metabolic pathways are elucidated by such investigations,86 their relevance to the human exposure conditions is problematic. Although alumina at such doses which negate tracheal-bronchial clearance may produce effects as a consequence of catalytic activity or surface area related thermodynamic instability, usual human exposure conditions produce neither such lung doses, disablement of clearance mechanisms, or signifi cant pathology. Thus, as with the halogenated aliphat ics, although alternate pathways and pathologies can be induced experimentally, under usual conditions of chronic human exposure, these phenomena are largely of academic interest. In contrast, the inhalation model approaches more closely the exposures encountered at work. Studies us ing this model to evaluate alumina's pulmonary bioreac tivity demonstrate that even the most thermodynami cally active forms x` a-nd 78 do not cause fibronodular change. Yet the results of Klosterkotter6 serve to cau tion against uncritical application of the inhalation model. Klosterkotter explicitly recognized that the doses he employed (ie, 33 g/m3 for eight hours a day for 286 days) represent an exposure level which was intolerable for his laboratory personnel.8 Ultimately, in assessing human health hazards, well designed studies of working populations potentially at risk assume considerable importance. Review of occupational exposures to (1) catalytically active large surface area, low temperature transitional aluminas (x- tj, 7) in aluminum chemical refineries; (2) high temperature 7, k, 5, and 0 transitional aluminas encountered in smelters since the late 1960s; and (3) high-fired a-aluminum oxide as found in potteries sug gest that of all these aluminas demonstrate minimal-- if any--fibrogenic potentials in man. It is ironic that, although concerns regarding 7-alumina's pulmonary fibrogenicity have persisted (eg, in the standard-setting process97) since the London studies, (1) a specific 7alumina, ie, the transitional form, was probably not actually studied by that group and (2) the other socalled 7-aluminas exhibited inconsistent biologic re sponses (eg, the nonreactivity of 7-AIOOH Cera hydrate * v the fibrogenic response to 7-AIOOH HX1010 gelati nous boehmite). The final irony is reflected in the obser vation that the only true exposure to a specific 7 transitional alumina (ie, by Klosterkotter) via inhala tion does not produce a specific pulmonary fibronodular response, but rather the nonspecific alveolar proteinosis. All the foregoing data place in high relief the propo sition that it is only through critical assessment of both experimental and human experience with environmen tal agents that we may understand such compounds' role in disease induction. On the basis of in vitro and in vivo experimental apd workplace studies under condi tions of human exposure, it is clear alumina's fibrogen icity is quite low regardless of which specific alumina is examined. Technical Note: Physical, Chemical, and Structural Nomenclature, Identification, and Behavior of Aluminas The Physical and Chemical Bases for Confusion The oxides, hydroxides, and oxyhydroxides of alumi num have been given a multiplicity of designations since aluminum oxyhydroxide was first chemically analyzed and identified by Vauquelin in 1802. Investigators gave different names to the same chemical compound or mineral form (cf Table 2); this led to confusion as different physical properties, eg, crystalline structure, were assigned to the same compound. For example, the minerals gibbsite and diaspore, identified in the first and third decades of the 19th century, were later con fused with their isomorphs, which were given the names boehmite and bayerite in the 1920s. To compound this multiplicity of appellations, the name hydrargillite was applied by the Europeans to gibbsite. Duplicative and inconsistent terminology ensued when Greek letter prefixes were attached to various aluminas for unrelated reasons or behaviors. Rankin and Merwin" in 1916 assigned the Greek letter prefix ^ to a high temperature alumina later shown to contain alkali or alkaline earth atoms. Haber99 in 1926 divided Preferred Chemical Formula and Name1* AK0H)a. alumina trihydroxide AlOQH aluminum oxyhydroxide Aluminum oxide TABLE 2 Companson of Physical and Chemical Nomenclature Applied to the Alumina Minerals VVV 000010515 Mineral Name" Formerly Applied Designation1* American System50-17 European System3* X-ray Crystaiiograph Classification1* Gibbsite or Hydrargil lite Bayerite Nordstrandite Boehmite Diaspore Corundum Alumina trihydrate Aluminum hydroxide Alumina trihydrate Aluminum hydroxide Randomite Alumina monohydrate Alumina monohydrate rt-Alumira , y a.fi -- a, y et.0 a yy ya y0 yy aa aa 332 Alumina-related Pulmonary Disease/Dinman aluminum oxide into an a and y series, depending upon the product of the oxide's calcination. Subsequently, Edwards et al30 assigned the prefix a to the more abundant hydroxide, whereas the less abundant alumina was given the (3 prefix; both appelations were applied without regard for structure. Later, as these aluminum compounds were used in industrial processes, different nationally based variant nomenclatures--North American or European--were used to describe the same compounds. The resulting confusion in chemical and mineral nomenclature is am ply demonstrated by Table 2. This ambiguous situation was further complicated when Ulrich31 in 1920 found that progressive heating of the hydroxide gave rise to a previously undescribed form which he called y. This material was later found by Stumpf et al3a to be but one of the several alumina transition forms x> 77> and y (Fig. 2). However, before these specific, individual forms were defined, the Greek prefix y, attached by Ulrich to these forms, came to be applied via common usage to all three low temperature calcination products of aluminum oxides and oxyhydroxides, ie, tj, x, and y. It was not until 1950 that Stumpf et al39 restricted the prefix y to one specific thermally induced transition form derived from gibbsite and boehmite formed between 500 and 850C (Fig. 2). In succeeding years, the identification of each of these thermal transitional reorderings was established and Greek alphabetical prefixes were given to these specific orms (Fig. 2). However, it must be recognized that what appears to be a straightforward sequence of individual, defined phases or polymorphs of aluminum oxides represents in reality thermodynamically unstable states of structural reorderings of the hydroxide lattice. Although these states are reasonably reproducible, even within a solid, there may occur simultaneously various domains char acterized by different degrees of structural reorderings. The type of transition form and the sequence of trans formation depends upon variables such as the structure of the precursor, rate of heating, particle size, and components or contaminants in the atmosphere. Accord ingly, unless details of all such variables are reported, critical evaluation and interexperimenter comparisons of biologic response are unreliable. The structural and compositional differences among these several transition forms, e.g., between rj and y forms, are small and difficult to distinguish. In attempt ing to identify precisely these low temperature transi tional forms, ij, x, and y, we are faced with a double dilemma. Not only are these transitional states identi fied with difficulty, but structural analysis cannot pre cisely quantify the ratio between the amorphous and crystalline states within a specific specimen. Ultimately, in considering these low temperature transition forms, one faces the reality that these aluminum oxides rep resent highly dynamic reorderings of crystalline struc ture and amorphous elements temporally and spatially distributed in a nonhomogeceous, random fashion. It should be readily apparent why, despite general accept ance of the Munster Symposium39 recommendation giv ing each transitional form an individual, specific Greek prefix designation (Fig. 2), present industrial/commercial nomenclature often fails to differentiate between GwdilltM Ttamn Afiwitrn ftnkteSu P/uuK.ln.., fivnrint Truuformiuonl VUi >1 ftlA. --'** tlr >l'C/ak. >Utaiow 1 1M. dry lir <!*C/afak <10 aim* b (gibbsite a1 BOEHMITE 0 D | GAMMA (alpha DELTA |thta[alpha (alpha ! DIASPORE -- ALPHA VVV 000010516 -------- 1--------- 11IIII1I' ' 100 200 300 400 500 600 700 800 900 1000 1100 1200 TEMPERATURE, C Pig, 2. Decomposition sequence of aluminum hydroxides. The transition forms (chi. eta. gamma, kappa, delta, theta) represent states of thermally induced structural reordering associated with dehydration. The x. y, and rj forms have been genetically referred to in the past as y alumina.3* Journal of Occupational Medicine/Volume 30 No. 4/April 1988 333 these low temperature transition forms. Given these multiple ambiguities arising from a highly dynamic system, we recommend that, rather than attempting to ascribe biologic effects to individual aluminum oxides, eg, to the y form, the transition forms tj, x. and 7 collectively be referred to as low temperature transi tional aluminas. To complete the confusion, international crystallo graphic convention prefers application of the prefix a to the closest packed--especially hexagonal--struc tures; the 7 prefix is given generically to the cubic packed structures.94 (Nordstrandite (/3-Al(0H)a) pos sesses a crystalline packing arrangement intermediate between gibbsite (7) and bayerite (a) and therefore is designated /3.) In summary, it should be readily apparent that the prefix 7 has been applied for a multiplicity of reasons both to crystalline alumina minerals as well as to the transitional form. In addition to the foregoing relatively well-defined crystalline minerals, various syntheses of aluminum hy droxides produce colloidal aluminas which easily coag ulate to a two-phase system gel, ie, a highly dispersed colloidal solid with molecular water occupying capillary interstices. In particular, one of these gelatinous alu minas, gelatinous boehmite, is pertinent to our concerns. It demonstrates minimal crystalline structure, consist ing of molecular water situated between the elemental structure layers. This leads to an enlargement of the basal spacings of boehmite. These gels can be dried to extremely fine (10~* /um) and porous particulates pos sessing extremely large surface areas, as large as 500 m /g. Functional Properties of Those Aluminas of Potential Biologic Interest Regarding a and 7 designations derived from the crystallographic convention, no apparent common prop erties with biologic implications are presently known to occur. Because they are applied to a diverse and large number of aluminas (Table 2), with different chemical and physical forms, any lack of commonality of biologic behavior is not unexpected. Concerning the thermally induced transitional forms / (Fig. 2), the physical-chemical properties of these forms . may be of importance in biologic systems. Heating alu mina minerals under specific conditions (Fig. 2) induces these transition forms; such forms characteristically demonstrate a progressive disorganization and reorga\ nization of crystalline structure as temperature rises | through the 250 to 850C range. Structurally, lattice / voids and a network of submicroscopic cracks and spaces ' open.34 , The newly formed surfaces presented by these fissures ; and voids result in large surface areas characteristic of :: the low temperature transitional forms (Fig. 3). Con comitant with the loss of water resulting from the combination of OH- ions (OH~ + OH" HflO + O), exposed Al+ sites are formed; these act as Lewis acid sites, ie, electron acceptors. Furthermore, certain re tained OH- ions act as proton donors, Brdnsted acid sites. Depending upon the local composition, 0~ or OH~ ions may also function as Brbnsted or Lewis bases. The aggregate of these physical-chemical alterations occur ring during thermal transformation is believed respon sible for catalytic activity of these alumina transition forms.36 The 7, tj, and x transition forms maximally manifest these crystalline disorderings; they likewise manifest the maximum catalytic activity among these transitional forms. As an additional consequence of these thermal trans formations leading to the transitional aluminas, at ap proximately 300 to 600C a marked increase in surface area occurs34 (Fig. 3). This is a result of the loss of over 30% of the mass without change in the external dimen sions of the crystals. With continued heating of these transitional aluminas beyond 850C, crystalline order begins to be re-established and chemical stoichiometry is restored. With these balances restored, catalytically active sites diminish and ultimately disappear. The voids and channels are diminished and surface area becomes markedly decreased (Fig. 3). This reordering and ther modynamic stabilization reaches a maximum with the formation of a-AU03, corundum.34 '. As a consequence of the dehydration, a remarkably large surface area forms. Concurrent with the rise in .surface area, there is proportionate increase in surface thermodynamic instability.36 It is not unreasonable to TEMPERATURE.*C Fig. 3. Specific surface area charges resulting from heat treatment of AKOHfe.34 suggest that the combination of chemical activity (ie, the acid-base character of the low temperature transi tional alumina surfaces) and the large surface area per se are important factors controlling bioreactivity. VVv 000010517 334 Alumina-related Pulmonary Disease/Dinman Acknowledgments We are indebted to Dr Karl Wefers for his patient assistance in our attempt to grain some understanding of the physical-chemical nature of the aluminas, to Ur T. B. Bonney and S. O. Epstein for their editorial assistance, to Dr* John Oilson and W. K. C. 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