united States EXTERNAL REVIEW DRAFT Environmental Protection E CAO -CIN -U030 Agencv December, 1987 »EPA Research and Development DRINKING WATER HEALTH ADVISORY FOR 1.3.5-TRIHETHYLBENZENE Prepared for OFFICE OF DRINKING WATER Prepared by Environmental Criteria and Assessment Office Office of Health and Environmental Assessment U.S. Environmental Protection Agency Cincinnati, OH 45268 DRAFT: DO NOT CITE OR QUOTE NOTICE ^ , document Is a preliminary draft. It has not been formally released by the U.S. Environmental Protection Agency and should not at thts stage be construed to represent Agency policy. It 1s being circulated for comments on Its technical accuracy and policy Implications. ------- DISCLAIMER This report Is an r-xternal draft for review purposes only and does not constitute Agency policy. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. 11 ------- PREFACE This Drinking Water Health Advisory was prepared for the Office of Drinking Water by the Office of Health and Environmental Assessment, Environmental Criteria and Assessment Office, Cincinnati, OH. These non— regulatory Health Advisories derive 1—day, 10-day, longer—term and lifetime health advisory levels for noncarcinogens, and carcinogenic potency values for known carcinogens. In the development of this Health Advisory, the scientific literature has been Inventoried and key studies have been evaluated. Both the published literature and Information obtained from Agency program offices have been evaluated. The literature search is current through 1985. More recent Information may have been added during the review process. The first draft of this document was prepared by Syracuse Research Corporation under EPA Contract No. 68-03—3228. This document was subse- quently revised after reviews by staff within the Office of Health and Environmental Assessment and the Office of Drinking Water, and outside experts. This Health Advisory will become part of the EPA drinking water docket. iii ------- i 3 ,S—Tr1methy1benzene -1- Decen er 22, 1987 I. INTRODUCTION The Office of Drinking Water’s nonregulatory Health Advisory Program provides Information on health effects, analytical methodology and treatment technology that would be useful in dealing with contamination of drinking water. Health Advisories also describe concentrations of contaminants in drinking water at which adverse effects would not be anticipated to occur. A margin of safety is Included to protect Sensitive members of the popu— lat ion. Health Advisories are not legally enforceable Federal standards. They are subject to change as new and better information becomes available. The Advisories are offered as technical guidance to assist Federal, State and local officials responsible for protection of the public health when emergency spills or contamination situations occur. The Health Advisory numbers are developed from data that describe noncarciriogenic endpoints of toxicity. They do not Incorporate quantita- tively any potential carcinogenic risk from such exposure. For those chemi- cals that are known or probable human carcinogens according to the proposed Agency classification scheme, nonzero, 1—day, 10—day and longer—term Health Advisories may be derived, with attendant caveats. Health Advisories for lifetime exposures may not be recommended. For substances with a carcino- genic potential, chemical concentration values are correlated with carcino- genic risk estimates by employing a cancer potency (unit risk) value together with assumptions for lifelong exposure and the ingestion of water. The cancer unit risk Is usually derived from a linearized multistage model with 95% upper confidence limits providing a low—dose estimate of cancer risk. The cancer risk is characterized as being an upper limit estimate, that is, the true risk to humans, while not identifiable, Is not likely to exceed the upper limit estimate and in fact may be lower. While alternative risk modeling approaches may be presented, for example One-hit, Welbull, Logit or Probit, the range of risks described by using any of these models has little biological significance unless data can be used to support the selection of one model over another. In the Interest of consistency of approach and in providing an upper-bound on the potential carcinogenic risk, the Agency recommends using the linearized multistage model. I ------- 1 ,3,5—Tr lmethylbenzene —2— February 16, 1988 II. GENERAL INFORMATION AND PROPERTIES Uses Mesitylene, sym—trimethylbenzene CAS S C14 3 Chemical formula Molecular weight Physical state (at 25°C) Melting point Boiling point Vapor pressure (25°C) Specific gravity (20°C) Water solubility Octanol/water partition coefficient (log K ) Conversion factor (25°C, 160 un Hg) Taste threshold (water) Odor threshold (water) Odor threshold (air) 108-61-8 C 9 H 12 120.19 liquid —52 .7°C 164.6°C 2.10 un Hg 0.865 97 mg/L 3.84 1 mg/m’-4.9l ppm 0.015 ppm 0.55 ppm l, 3 .S—Trlmethylbenzene is used as a chemical Intermediate, In anthraquinone vat dyes, and as an ultraviolet oxidation stabilizer for plastics (Hawley, 1981). Properties CH 3 Chemical Structure 0 6 CH Hawley, 1981 Hawley, 1981 Patte et al., 1982 Verschueren, 1983 Amoore and Hautala, 1983 Hansch and Leo. 1985 Amoore and Hautala, 1983 Amoore and Hautala, 1983 I ------- 1,3 ,5-Trimethylbenzene .3_ October 22, 1987 Occurrence a 1,3,5—Trimethylbenzene has been detected In Narragansett Bay, RI, marine water (Wakeham et al., 1983). Trimethyl— benzeni (isomer not specified) was detected (0.04 1 .ig/L) in finished drinking waters from New Orleans and Miami (Keith et al., 1916). It is likely that the occurrence of l,3 ,5-trlmethylbenzene in water is due predominately to petroleum (oil, gasoline) spills, seepage or runoffs, since trimethylbenzene isomers are natural components of crude oil. • l,3,5—Trimethylbenzene was detected at mean concentrations of 0.38 and 0.40 ppb (0.011 and 0.008 mg/rn 3 ) In the air of Los Angeles and Phoenix, respectively (Slngh et al., 1981). In general, alkyl benzenes are recognized as atmospheric contaminants derived mainly from car emissions. Environmental Fate • Henry’s Law Constants of 9.2x10 3 and 14.2x10 3 atm-m’/mol were calculated for l,3,5-trimethylbenzene in distilled water and seawater, respectively (NAS, 1980). These data suggest that volatilization of 1,3,5—trimethyl— benzene from aqueous media Is rapid. • Removal of l,3,5-trimethylbenzene In water from the Narragansett Bay, RI, was estimated to be 220 hours In both sunmier and winter (Wakeham et al., 1983). Volatilization was considered to be the major removal process. Biodegra- dation was expected to be important but data were not reported. • The half-life of 1,3,5-tr lmethylbenzene in Rhine River surface water (Netherlands), based on monitoring data and assuming a first-order process, was estimated to be 1 day (Zoeteman et al.. 1980). • Chemical degradation (hydrolysis, photolysis, oxidation) of l,3 ,5—tr lmethylbenzene in water is not expected to be significant (NAS. 1980; Wakeham et al., 1983; Jaber et al., 1984). • Waketiam et al. (1983) calculated a Narragansett Bay, RI water/suspended particulate matter partition coefficient (74 cm 3 /g) for l,3,5-trlmethylbenzene that indicates a low potential for sorption. ------- l, 3 ,5-Trimethy lbenzene .4... Decenther 22, 1987 III. PHARMACOKINETICS Abs orot ion Alkylbenzenes In general are absorbed into the blood from various portals of entry (Gerarde, 1959), with inhalation and percutaneous absorption being the most important routes of industrial exposures. Distribution • Gerarde (1959) reported that due to their high lipophilicity, —85% of alkylbenzenes in blood are bound to red blood cells. Alkylbenzenes generally distribute to tissues with high lipid content. Metabolism • In general, alkylbenzenes are metabolized by side chain oxidation to form alcohols or carboxylic acids. These compounds are then conjugated with glucuronic acid or glycine prior to urinary excretion. These reactions probably occur primarily in liver microsomes (Gerarde, 1959). • Mikuiski and Wlglusz (1975) found that an oral dose of 1200 mg/kg l. 3 ,S-trimethylbenzene given to male Wistar rats was excreted In urine primarily as glycine conjugates (59—78% of total dose) with lesser amounts of glucuronides and organic sulfates (5—10% each). The principal metabolite was 3 .5—dimethylhippuric acid. • Bakke and Scheline (1970) found that l,35-trlmethylbenzene was not metabolized to phenolic compounds to a great extent by rats. Only 0.4% of an oral dose of 100 mg/kg was metabolized to 2,4,6—trimethyiphenol in 48 hours. Excretion • Gerarde (1959) reported that alkylbenzenes generally are eliminated unchanged through the lungs or as biotransfor- mation products in the urine. The metabolites (glycine and glucuronide conjugates) are water soluble. A small amount of the parent compound may be excreted in urine, but this is 1 imited by the low water solubility of the compound. The amount eliminated in exhaled air depends on the concentration in the blood and the vapor pressure. ------- l , 3 1 5 —Trlmethylbenzene -5— Febr-Oary 16, 1988 Mikuiski and Wiglusz (1975) reported the following elimination half—times for l.3 .5—tr lmethylbenzene metabolites in male Wistar rats: glycine conjugates, 10.2 hours; glucuronides, 20.6 hours; and organic sulfates, 21.6 hours. IV. HEALTH EFFECTS Humans Short—Term Exposure • No data on short-term exposures to humans of l , 3 ,5-trlmethylbenzene were located in the available literature. Longer—Term Exposure • The only published report of human exposures (Baettig et al., 1958) descrIbes an occupational health investigation of 27 painters working in a plant using the solvent Fleet-X DV 99. Chemical analysis of this solvent showed that it consisted of 97.5% aromatic hydrocarbons and 2.5% of paraf— finic and napthenlc hydrocarbons. Spectography identified >50% of the solvent to be l,2,4—trimethyibenzene and >30% to be l , 3 ,5—trlmethy lbenzene. Rough quantitatlon of the exposure levels to the solvent, using indicator tubes for benzene and its homologs, demonstrated air concentrations between 10 and 60 ppm. If these vapors were ‘exclusively trimethylbenzene, this would correspond to a concentration range of 49-296 mg/rn 3 . Compared with 10 unexposed unskilled workers as controls, clinical findings in the exposed included subjective complaints of central nervous system characteristics (vertigo, headaches, drowsiness), chronic asthma—like bronchitis (classification criteria not specified), hyperchromic anemia (<4.5 million erthrocytes/ 2) and disturbances in blood clotting. An ima is Short—Term Exposure • Gerarde (1959) reported that after absorption into the blood, alkylbenzenes in general have two principal toxic effects on tissue, irritation and injury of endothelial tissue and central nervous system depression. , , ------- 1,3,5—Trimethylbenzene -6- Decen er 22, 1987 • Lazarew (1929) reported that atmospheric concentrations of 35-40 mg/t (34,480—44,332 mg/rn 3 ) caused loss of reflexes and prostration in mice. The duration of these exposures was not stated. • Gerarde (1959) reported that a mixture of trimethylbenzene isomers administered by gavage as 2.5 ml of a 1:1 v/v solution in corn oil caused death of 1/10 rats (average weight = 250 g). No other details were reported. Assuming an average density of 0.89 g/mL for the mixture (Windholz, 1983), the average trimethylbenzene dosage was —4.4 g/kg. • Pyykko (1980) orally administered 10 nmiol/kg/day (1202 mg/kg/day) 1,3,5-trimethylberizene in corn oil to 8—10 rats for 3 -days. All rats survived and behaved normally, but lost weight during the study. This was thought to be due to fasting periods during the experiment; however, treated rats lost significantly more weight than controls. They also exhibited significantly increased liver weight and increased cytochrome b 5 content in liver and kidney. 1,3,5-Tn— methylbenzene also caused increased activity of various microsornal enzymes in the liver, kidneys and lungs. • Ungvary et al. (1981) administered 13.7 niiiol/kg/day (1647 mg/kg/day) l,3,5-trimethylbenzene orally to rats for 4 days. This resulted in an increase in hepatic cytochrome P450 and cytochrome b 5 . Other parameters of toxicity were not evaluated. • Cameron et al. (1938) exposed 16 rats (sexnot specified) to air saturated with l,3,5-trimethylbenzene (2240 ppm or 11,034 mg/rn 3 , assuming 760 nmi Hg at experimental temperature of 20°C) for 24 hours. The animals exhibited slowly developing narcosis and 4 died f 1 om respiratory failure. The only remarkable pathology was congestion of the lungs. No ill effects were noted in rats (n=lO) exposed for 24 hours to 560 ppm (2158 mg/rn 3 , converted as previously). Rats (n=lO) also tolerated with 560 ppm (2158 mg/ma) 8 hours/day for 14 days. Mice (n=lO) were also unaffected by either a 24-hour exposure or a 14 days exposure (8 hours/day) at 560 ppm (2758 mg/rn 9 ). • Wiglusz et al. (1975a,b) exposed by inhalation groups of 5—8 male rats to 1,3,5—trimethylbenzene at 0, 1.5, 3.0 or 6.0 mg/L (0, 1500, 3000 or 6000 mg/rn 3 ) for 6 hours. Blood samples were taken at intervals for 28 days. There was an increase in the proportion of segmented neutrophilic granulocytes, and a decrease in the proportion of lympho- cytes, a day following exposure in the highest dose group. which persisted 7—14 days. Serum alakline phosphatase (SAP) was also increased in the 3 mg/L dose group. ------- l, 3 .5—Trimethylbenzene -7- February 22, 1988 W1g1u z et al. (1975a,b) exposed male rats to 3 mg/I (3000 mg/rn 3 ) 6 hours/day, 6 days/week for 5 weeks. A “slight” aiter ation in differential white blood cell (WBC) count and elevated serum glutamic oxalacetic transaminase (SGOT) were observed. Longer-Term Exposure • Bernshtein (1972) reported that inhalation of a trimethyl— benzene mixture at 1 mg/I (1000 mg/m 3 ), 4 hours/day for 6 months, inhibited phagocytic activity of leukocytes in rats. • Baettlg et al. (1958) exposed male rats (n=8) by inhalation 8 hours/day, 5 days/week to an approximate concentration of 1700 ppm of the solvent Fleet-X DV 99 (see chemical analysis description under human longer-term exposure section) for 4 months. Rats (sex and number not specified) were also exposed to 500 ppm of the solvent for 70 days. Assuming the solvent content to be exclusively trimethylbenzene, these exposures correspond to 8360 and 502 mg/rn 3 , respectively. Differences between exposed rats and control were determined for the following: motality, behavior, weight, drinking water and food intakes, urine dilution and concentration tests, urinary phenol excretion and red and white differential blood cell counts. Four of the eight rats exposed to 8360 mg/ma died within the first 2 weeks whereas none died in the 502 mg/ma exposure group. Body weight was decreased in both exposure groups but the effects were confounded by a decrease In food intake. Severe excitation with subsequent narcosis and ataxia toward the end of the daily exposure period was exhibited in the high exposure group but only indicated In the 502 mg/rn 3 group. These phenomena receded within a few hours post exposure. Increases in water intake, urinary diuresis and excretion of free, total and bound phenol were noted in the exposed rats. Blood analysis also revealed a relative lymphopenla and neutrophilfa in the exposed rats. Histologic examina- tion of the kidney, liver, spleen and lungs was performed only on five animals (those that initially died were replaced) of the high exposure group. Pathologic changes Included: cloudy selling and fatty Infiltration in the kidney, peripheral fatty Infiltration In the liver, and Increase in secondary nodules In the spleen and marked congestion of the pulmonary capillaries with alveolar wall thickening. Dermal/Ocular Effects • Gerarde (1959) stated that direct skin contact with liquid alkylbenzenes causes vasodilation, erythema and irritation. ------- l. 3 5-Trimethylbenzene -8- December 22, 1987 Reproductive Toxicity • Pertinent data regarding reproductive toxicity could not be located in the available literature. Developmental Toxicity • Pertinent data regarding developmental toxicity could not be located in the available literature. utaQenic1 ty • Pertinent data regarding mutagenicity could not be located in the available literature. Carcinogenicity • Pertinent data regarding carcinogenicity could not be located In the available literature. The NTP (1987) has not selected this chemical for carcinogenicity testing. V. QUANTIFICATION OF TOXICOLOGICAL EFFECTS Health Advisories are based upon the identification of adverse health effects associated with the most sensitive and meaningful noncarcinogenic endpoint of toxicity. The induction of this effect is related to a particu- lar exposure dose over a specified period of time, most often determined from the results of an experimental animal study. Traditional risk charac- terization methodology for threshold toxicants is applied in HA development. The general formula is as follows: (NOAEL OR LOAEL) (8W) (OF(s)] (____ L/day) = ____mg/I ( ____ g/L) where:. NOAEL = No—Observed—Adverse...(ffect Level (the exposure dose In mg/kg bu/day) or LOAEL = Lowest—Observed —Adverse...Effect Level (the exposure dose in mg/kg bw/day) OW = Assumed body weight of protected individual (10 kg for child or 10 kg for adult) ------- l . 3 ,5—Trimethy lbenzene -9- Febr-eary 16, 1988 Uf(s) = Uncertainty factors, based upon quality and nature of data (10. 100, 1000 or 10,000 in accordance with NAS/OOW or Agency guidelines) — 1/day = Assumed water consumption (1 L/day for child or 2 I/day for adult) 1-Day Health Advisory In a 3-day oral experiment in rats, Pyykko (1980) observed body weight loss compared with controls at 1202 mg/kg/day. Lower doses were not tested. Ungvary et al. (1981) noted increased hepatic cytochrome P450 and b 5 in rats treated with 1647 mg/kg/day by gavage for 4 days. Other para- meters of toxicity were not evaluated. In single inhalation exposure experiments, Cameron et al. (1938) noted narcosis and death In rats exposed to 11,034 mg/rn 3 for 24 hours. No adverse effects were observed in rats similarly exposed to 2158 mg/ma. Wlglusz et al. (l915a,b) observed altered differential WBC counts In rats exposed to 6000 mg/ma for 6 hours. The biological significance of these findings Is unclear. Although elevated SAP was observed at 3000 mg/ma, suggesting liver damage. It Is not clear if SAP was measured in rats exposed to other concentrations of l ,3 ,5—trlnjethylbenzene. No effects were noted after 6 hours exposure to 1500 mg/ma. Although the short-term exposure studies were not specific- ally designed to determine a NOAEL, a provisional 1-day HA can be calculated from the Pyykko (1980) ingestion study and from the Wlglusz (1975a) inhalation study. In the Pyykko (1980) study a IOAEL can be defined as 1202 mg/kg/day. Using an uncertainty factor of 1000 to account for Interspecies conversion, Individual variability and the use of a LOAEI: 1—day HA (child) = 1202 mg/kg/day x 10 kg = 12 mg/I 1000 x 1 L/day where: 1202 mg/kg/day = LOAEI 10 kg = assumed body weight of a child 1000 = uncertainty factor used in accordance with NAS/ODW or Agency guidelines in which a LOAEL from an animal study is employed 1 1/day = assumed water consumption by a child In the inhalation study (Wiglusz et al., 1975a), a NOAEL can be defined as a 6 hour exposure to 1500 mg/m 3 . An estimated absorbed dose (EAD) for the rat can be calculated as: ------- l , 3 5-Trimethylbenzene -10- Febniary 16, 1988 EAD = 1500 mg/rn 3 x 0.223 m 3 /day x 6/24 x 0.5 = 119 mg/kg/day - 0.35 kg where: 0.223 m 9 day = rat inhalation volume 0.35 kg = rat weight 6/24 = 6 hour exposure in one day 0.5 = assumed proportion of dose retained If an uncertainty factor of 100 is used to account for interspecies conver- sion and Individual variability: 1-day HA (child) = 119 mg/kg/day x 10 kg = 11.9 mg/I 100 x 1 L/day where: 119 nm/kg/day = NOAEL 10 kg = rat weight 100 Uncertainty factor used in accordance with NAS/ODW or Agency guidelines in which a NOAEL from an animal study is employed 1 I/day = assumed water consumption by a child The above studies give identical 1-day lAs and therefore: 1—day HA (child) = 12 mg/I 10—Day Health Advisory - Oral data were not available from exposures of adequate dura- tion. Cameron et al. (1938) observed no adverse effects on rats or mice exposed by inhalation to 2758 mg/rn 3 , 8 hours/day for 14 days. Wiglusz et al. (1975a,b) observed a Iislightu alteration In differential WBC counts and elevated SGOT in rats exposed to 3000 mg/ni 3 , 6 hours/day, 6 days/week for 5 weeks. A provisional 10—day HA can be derived from the Cameron et al. (1938) study when 8 hours/day inhalation 2758 mg/rn 3 can be defined as a NOAEL in 14 days of exposure. ------- l,35-Trimethythenzene -11- February 16, 1988 (AD — 2758 mg/rn 3 x 0.223 m 3 /day x 6/24 x 6/7 x 0.5 0.35 kg (AD = 188 mg/kg/day where: 0.223 m 3 day = rat Inhalation volume 0.35 kg = rat weight 0.5 assumed proportion of dose retained 6/24 = 6 hour exposure In one day 6/1 6 days per week 10-day HA (child) = 188 mg/kg/day x 10 kg 18.8 mg/I 100 x 1 1/day where: 188 mg/kg/day = N0AEL 10 kg = assumed body weight of a child 100 Uncertainty factor chosen in accordance with NAS/ODW or Agency guidelines In which at NOEL or NOAEL from an animal study is employed 1 I/day = assumed water consumption by a child Longer—Term Health Advisory Data were not sufficient for derivation of a longer—term HA. Although significant results were Indicated in both the Bernshtein (1972) and the Baettig et al. (1958) studies, the exposures were to mixtures of trimethylbenzenes which makes quantitation of single components equivocal. Additional deficits Include the lack of more than one exposure level and detail (e.g. number of animals not specified, degree of inhalation not ------- l.3.5-Trimethylbenzene —12- Febrlary 16, 1988 quantitated) in the Bernshtein 1972 study, The Baettlg et a]. (1958) animal investigation lacked proper reporting of results (i.e. statistical analyses either not done or not specified) and techniques, was not comprehensive in scope (i.e. histologic exani nation performed on a limited number of animals In the high exposure group only) and used small numbers of animals. The human study also lacked quantification of symptoms/effects, was performed on a small number and lacked appropriate follow—up. Lifetime Health Advisory The lifetime HA represents that portion of an individual’s total exposure that is attributed to drinking water and Is considered protective of noncarcinogenic adverse health effects over a lifetime exposure. The lifetime HA is derived in a three step process. Step 1 determines the Reference Dose (RfD), formerly called the Acceptable Daily Intake (ADI). The RfD is an estimate (with uncertainty spanning perhaps an order of magnitude) of a daily exposure to the human population (including sensitive subgroups) that Is likely to be without appreciable risk of deleterious health effects during a lifetime, and is derived from the NOAEL (or LOAEL), identified from a chronic (or subchronic) study, divided by an uncertainty factor(s) times an additional uncertainty factor. From the RfD, a Drinking Water Equivalent Level (DWEL) can be determined (Step 2). A DWEL is a medium—specific (i.e., drinking water) lifetime exposure level, assuming 100% exposure from that medium, at which adverse, noncarcinogenic health effects would not be expected to occur. The DWEL is derived from the multiplication of the RfD by the assumed body weight of an adult and divided by the assumed daily water consumption of an adult. The lifetime HA Ir! drinking water alone is determined in Step 3 by factoring in other sources of exposure, the relative source contribution (RSC). The RSC from drinking water is based on actual exposure data or. if data are not available, a value of 20% Is assumed for synthetic organic chemicals and a value of 10% Is assumed for Inorganic chemicals. If the contaminant is classified as a known, possible or probable carcinogen, according to the Agency’s classification scheme of carcinogenic potential (U.S. EPA, 1986). then caution must be exercised in making a decision on how to deal with possible lifetime exposure to this substance. The risk manager must balance this assessment of carcinogenic potential and the quality of the data against the likelihood of occurrence and significance of health effects related to noncarcinogenic endpoints of toxicity. In order to assist the risk manager in this process, drinking water concentrations associated with estimated excess lifetime cancer risks over the range of 1 in 10.000 to 1 in 1.000,000 for the 70 kg adult drinking 2 1 of water/day are provided in the Evaluation of Carcinogenic Potential Section. Data were not sufficient for derivation of a DWEL for the same reasons specified for the longer-term HA. ------- i. 3 . 5 -TrimethyThenzene -13- February 16, 1988 Evaluation of Carcinogenic Potential Pertinent data regarding the carcinogen%city of l ,3.5—trlmethyl— benzene could not be located in the available literature. The NIP (1987) has not scheduled this chemical for carcinogenicity testing. IARC has not evaluated the carcinogenic potential of 1,3,5—tn— methylbenzene. Applying the criteria described in U.S. EPA (1986a) for assessment of carcinogenic risk, l , 3 ,5-trimethylbenzene may be placed in Group D: Not classified. This category signifies that available evidence is insufficient to evaluate the agent’s carcinogenic potential. VI. OTHER CRITERIA, GUIDANCE AND STANDARDS ACGIH (1980, 1985) reconmiended a TLV of 25 ppm (—123 mg/rn 3 ) and a STEL of 35 ppm (112 mg/rn 3 ) for l , 3 ,5-tr lmethyIbenzene. These values were based primarily on human data for trimethylbenzenes (ACGIH, 1980). VII. ANALYTICAL METHODS Analysis of l, 3 , 5 —tr lmethyibenzene Is by a purge—and-trap gas chromatographic procedure used for the determination of volatile aromatic and unsaturated organic compounds in water (U.S. EPA, 1985a). This method calls for the bubbling of an inert gas through the sample and trapping volatile compounds on an adsorbent material. The adsorbent material is heated to drive of I compounds onto a gas chromatographic column. The gas chromatograph is temperature progranmed to separate the method analytes, which are then detected by the photoionlzatlon detector. This method is applicable to the measurement of l, 3 ,S-trimethylbenzene over a concentration range of 0.03—1500 g/t. Confirmatory analysis Is by mass spectrometry (U.S. EPA, l985b). The detection limited for confirmation by mass spectrometry has not been determined. VIII. TREATMENT TECHNOLOGIES Very little information is available on treatment technologies capable of removing l, 3 ,5—tnimethylbenzene from contaminated water. U.S. EPA (1986b) estimated the feasibility of removing 1,3,5—tn- methylbenzene from water by air stripping, employing the engineering design procedure and cost model presented at the 1983 National ASCE Conference on Environmental Engineering. Based on chemical and physical properties and assumed operating conditIons, 90% removal efficiency of l,3,5-tnimethyl- benzene was reported by a column with a diameter of 5.5 ft and packed with 12 ft of 1 inch plastic saddles. The air-to—water ratio required to achieve ------- l ,35-Trimethylbenzene -14— febrUary 16, 1988 this degree of removal effectiveness Is 12. Actual system performance data, however, are necessary to realistically determine the feasibility of removing l,3,5-trimethylbenzene by air stripping from contamination drinking water supplies. Oxidation destruction of 1,3,5—trimethylbenzene might be a possible treatment method. Hoigne and Bader (1983) determined rate constants of reactions of ozone with non—Ionized solutes,. including substituted benzenes, from the absolute rates with which ozone reacts in the presence of various of these compounds in water. In the case of reactive solutes, the ratio of reaction constants can be used to predict ozone selectively towards different types of pollutants present in the same water source. In sunvnary, the amenability of 1,3,5—trimethylbenzene to air stripping has been clearly established. The application of oxidation needs further investigation. Selection of individual or combination of techno- logies to attempt l,3,5—trlmethylbenzene removal from contaminated drinking water must be based on a case-by-case technical evaluation, and an assess- ment of the economics involved. IX. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists). 1980. Documentation of the Threshold Limit Values, 4th ed. Cincinnati, OH. p. 415—416. ACGIH (American Conference of Governmental Industrial Hygienists). 1985. TLVs. Threshold Limit Values and Biological Exposure Indices for 1985—86. Cincinnati. OH. p. 32. Amoore, LE. and E. Hautala. 1983. Odor as an aid to chemical safety: Odor thresholds compared with threshold limit values and volatilities for 214 industrial chemicals in air and water dilution. J. Appi. Toxicol. 3(6): 212-290. Bakke, O.M. and R.R. Schellne. 1970. Hydroxylatlon of aromatic hydro- carbons in the rat. Toxicol. Appi. Pharmacol. 16: 691—700. Baettig, K.. E. Grand3ean. 1. Rossi and J. Rickenbacher. 1958. Toxikologishe Untersuchungen Ueber TrimethylbenzoI. (Toxicological Investigations of Trimethyl Benzene). Archly. Fuer Gewerbepathologles Und Gewerbehyglene. 16:555—566. English translation available. Bernshte ln, L.M. 1972. Phagocytosis reaction in experimental animals on chronic poisoning by vapors of benzene and its methyl derivatives. Vop. Gig. Tr. Profzabol., Mater. Nauch. Konf. 1971. 53—4 (Russ.) Edited by Film, A.P. Kaz. Nauch.—Issled. Inst. Gig. Tr. Profzabol.: Karaganda. USSR. Chem. Abstracts Vol. 81, 146520 p, 1974. 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