Urine Methyl Hippuric Acid Levels in Acute Pesticide Poisoning: Estimation of Ingested Xylene Volume and Association with Clinical Outcome Parameters

To determine the relationship between the oral ingestion volume of xylene and methyl hippuric acid (MHA) in urine, we measured MHA in 11 patients whose ingested xylene volume was identified. The best-fit equation between urine MHA and ingested amount of xylene was as follows: y (ingested amount of xylene, mL/kg) = −0.052x² + 0.756x (x = MHA in urine in g/g creatinine). From this equation, we estimated the ingested xylene volume in 194 patients who had ingested pesticide of which the formulation was not available. Our results demonstrated that oxadiazole, dinitroaniline, chloroacetamide, organophosphate, and pyrethroid were xylene-containing pesticide classes, while the paraquat, glyphosate, glufosinate, synthetic auxin, fungicide, neonicotinoid, and carbamate classes were xylene-free pesticides. Sub-group univariate analysis showed a significant association between MHA levels in urine and ventilator necessity in the pyrethroid group. However, this association was not observed in the organophosphate group. Our results suggest that MHA in urine is a surrogate marker for xylene ingestion, and high urine MHA levels may be a risk factor for poor clinical outcome with some pesticide poisoning.

Hippuric Acid Levels in Paint Workers at Steel Furniture Manufacturers in Thailand

BACKGROUND: The aims of this study were to determine hippuric acid levels in urine samples, airborne toluene levels, acute and chronic neurological symptoms, and to describe any correlation between urinary hippuric acid and airborne toluene. METHODS: The hippuric acid concentration in the urine of 87 paint workers exposed to toluene at work (exposed group), and 87 nonexposed people (control group) was studied. Study participants were selected from similar factories in the same region. Urine samples were collected at the end of a shift and analyzed for hippuric acid by high performance liquid chromatography. Air samples for the estimation of toluene exposure were collected with diffusive personal samplers and the toluene quantified using gas-liquid chromatography. The two groups were also interviewed and observed about their work practices and health. RESULTS: The median of the 87 airborne toluene levels was 55 ppm (range, 12-198 ppm). The median urinary hippuric acid level was 800 mg/g creatinine (range, 90-2547 mg/g creatinine). A statistically significant positive correlation was found between airborne toluene exposure and urine hippuric acid levels (r = 0.548, p < 0.01). Workers with acute symptoms had significantly higher hippuric acid levels than those who did not (p < 0.05). It was concluded that there was a significant correlation between toluene exposure, hippuric acid levels, and health (p < 0.001). CONCLUSION: There appears to be a significant correlation between workers exposure to toluene at work, their urine hippuric acid levels, and resulting symptoms of poor health. Improvements in working conditions and occupational health education are required at these workplaces. There was good correlation between urinary hippuric acid and airborne toluene levels.

Urinary Hippuric Acid and trans,trans-Muconic Acid Levels According to Commuting Mode and Duration, Residential Environment, and Intake of Preservative-Added Foods and Beverages in University Students / 대한산업의학회지

OBJECTIVES: Automobile exhaust gases contain benzene and toluene, which are excreted in human urine as trans,trans-muconic acid and hippuric acid, respectively. Sorbic acid and benzoic acid, used as food preservatives, are also metabolized into trans,trans-muconic acid and hippuric acid in the human body. The purpose of this study is to estimate the level of benzene and toluene exposure according to the commuting mode and duration, residential environment, and preservative-added foods intake in university students who are not occupationally exposed to benzene or toluene. METHODS: Spot urine samples were collected from 211 university students who had no occupational exposure to volatile organic compounds. Information about their smoking history, residence type, traffic environments, commuting mode and duration, and their intake of bottled or canned food or beverages was gathered through a self-administered questionnaire. Urinary concentrations of trans,trans-muconic acid and hippuric acid were measured and statistically correlated to the individual's life style factors. RESULTS: There was no significant difference in the urinary concentrations of trans,trans-muconic acid or hippuric acid according to the smoking history. Mean urinary concentration of hippuric acid in females was higher than that found in males. Subjects living in districts with a population density of 1,000~4,999 people/km2 showed the highest urinary hippuric acid level; individuals living in cities of 5,000~9,999 people/km2 population density were next. The mean urinary trans,trans-muconic acid concentration was higher in students who were living where traffic jams are common compared to those who did not, and in subjects whose residence were within 149 m from a 4-lane road compared to those whose residence was not. However, neither mode nor duration of the commute showed any effect on the urinary trans,trans-muconic acid or hippuric acid concentrations of the students. Urinary hippuric acid levels increased when consuming canned fruit or canned coffee, and urinary trans,trans-muconic acid levels increased when consuming fruit juices or pickled radishes. CONCLUSIONS: The inhalation of vehicle exhaust and the ingestion of canned or pickled food may increase urinary hippuric acid and trans,trans-muconic acid levels in individuals who are not occupationally exposed to benzene or toluene.

Estudo retrospectivo dos níveis de ácido hipúrico urinário em exames de toxicologia ocupacional / A retrospective study analysis of urinary hippuric acid levels in occupational toxicology exams

O ácido hipúrico é o principal metabólito do tolueno, solvente amplamente utilizado em processos industriais e com importantes efeitos tóxicos, fato que justifica a preocupação em monitorar regularmente sujeitos com risco de exposição ocupacional a este solvente. O objetivo deste trabalho foi avaliar os níveis de ácido hipúrico encontrados em trabalhadores submetidos à monitorização biológica. Foi realizado um estudo retrospectivo com dados dos anos de 2002 a 2005, no qual foram analisados os resultados e a situação do empregado na oportunidade do exame (periódico, demissional e admissional). Os resultados indicam uma redução significativa nos níveis de ácido hipúrico em 2005. Exames periódicos obtiveram resultados superiores aos exames admissionais e demissionais, e não foi verificada diferença significativa nas proporções dos sujeitos agrupados de acordo com a situação funcional em cada um dos intervalos estabelecidos segundo o valor de referência e o índice biológico máximo permitido. Os níveis de ácido hipúrico detectados indicam um baixo de risco de exposição ao tolueno na população avaliada, provavelmente em decorrência da preocupação crescente com a implantação de medidas de higiene ocupacional.

Hippuric acid is the primary metabolite of toluene, a solvent widely used in industrial processes with considerable toxic effects, a fact which justifies regularly monitoring individuals with occupational exposure to this solvent. This work aims at evaluating urinary hippuric acid levels found in workers subject to biological monitoring. A retrospective study was carried out with data referring from 2002 to 2005, in which exams results and employment status were analyzed (periodic, post-employment, and pre-employment exams). Results indicate a significant reduction in hippuric acid levels for 2005. Periodic exams presented higher results than pre-employment and post-employment exams. No significant difference was found in individuals grouped according to their status in each of the established intervals, their reference numbers, and maximum biological levels allowed. Hippuric acid levels detected indicate low risk of toluene exposure for the population under evaluation, probably due to a growing concern with the deployment of measures regarding occupational hygiene.

Effects of the Exposure to Polycyclic Aromatic Hydrocarbons or Toluene on Thiobarbituric Acid Reactive Substance Level in Elementary School Children and the Elderly in a Rural Area / 예방의학회지

OBJECTIVES: Polycyclic aromatic hydrocarbons (PAH) and toluene have been reported to induce reactive oxygen species and oxidative stress. This study was performed to investigate the effects of low level exposure to PAHs or toluene on the lipid peroxidation level in elementary school children and the elderly in a rural area. METHODS: Forty seven elementary school children and 40 elderly people who were living in a rural area and not occupationally exposed to PAH or toluene were the subjects of this study. Information about active or passive smoking and diet was obtained using a self-administered questionnaire. The urinary 1-hydroxypyrene (1-OHP), 2-naphthol, hippuric acid and thiobarbituric acid reactive substance (TBARS) concentrations were measured, and these values were corrected with the urinary creatinine concentration. RESULTS: In school children, the geometric means of the urinary 1-OHP, 2-naphthol, hippuric acid and TBARS levels were 0.02 ymol/mol creatinine, 0.47 micron mol/mol creatinine, 0.14 g/g creatinine and 0.95 micron mol/g creatinine, respectively. Those values for the elderly were 0.07 micron mol/mol creatinine, 1.87 micron mol/mol creatinine, 0.11 g/g creatinine and 1.18 micron mol/g creatinine, respectively. The mean levels of urinary 1-OHP, 2-naphthol and TBARS were significantly higher in the elderly subjects than in the children. The urinary TBARS level was not correlated with the urinary 1-OHP, 2-naphthol and hippuric acid, but they were correlated with the age of the subjects. CONCLSIONS: These results suggest that low level inhalation exposure to PAH or toluene does not markedly increase lipid peroxidation, and age is a significant determinant of lipid peroxidation.

Avaliação dos riscos associados ao uso do xilol em laboratórios de anatomia patológica e citologia / Assessing risks concerning the use of xylol in cytology and pathology laboratories

Neste estudo, realizou-se uma avaliação do risco ocupacional relacionado ao uso de xilol, ao qual estão expostos técnicos de oito laboratórios de citologia e anatomia patológica que atendem a população do Recife e de cidades do interior de Pernambuco. A coleta das informações deu-se por meio de questionários que podiam ser respondidos marcando-se alternativas de múltipla escolha. Deu-se destaque às informações decorrentes do uso do xilol relacionadas à saúde ocupacional e à percepção de risco na manipulação e no descarte dos rejeitos. Os resultados mostraram que a utilização de equipamentos de proteção individual e coletiva está sendo negligenciada. Dentre os entrevistados, 80% observaram mudanças na saúde após alguns anos de exposição ao xilol. Mesmo assim, apenas 6,6% deles fazem controle anual da presença de xilol no organismo pela dosagem de ácido metilhipúrico na urina. Constatou se que 76,6% dos entrevistados descartam o resíduo diretamente na pia, pois não existe um local para descarte de rejeitos. Frente aos dados encontrados, sugere-se que há necessidade de educar o trabalhador numa visão prevencionista em relação aos riscos ocupacionais e ambientais provenientes do uso deste agente químico.

In this study a diagnosis of occupational exposure related to xylol use bytechnicians in cytology and anatomic pathology was carried out in eight laboratories which care for the population of Recife and towns in the interior of the state of Pernambuco. Data were obtained by multiple choice questionnaires. Emphasis was given to information concerning occupational health and perception of risk when using xylol and disposing waste. The results showed that personal and collective protection equipment have being neglected. Eighty percent of the people interviewed had noticed changes in health after they had been exposed to xylol for some years. However, only 6.6% of them went through annual evaluation to check the presence of xylene in their organisms, by methyl hippuric acid determination in urine. It was noticed that 76.6% of the people interviewed disposed waste directly into a sink, as there was not a proper place for waste disposal. Data showed the need for workers training on a preventive view in relation to occupational and environmental risks.

Effect of Sodium Benzoate on Change of Urinary Hippuric Acid and Methyl Hippuric Acid among Workers Coexposed to Toluene and Xylene / 대한산업의학회지

OBJECTIVES: This study was performed to investigate the effect of drink containing sodium benzoate on the change of urinary hippuric acid (UHA) and methyl hippuric acid (UMHA) excretion among workers coexposed to low toluene and xylene. METHODS: Study subjects were 55 male shipbuilders who were divided into 3 groups; nonexposed group (n=10, who were not exposed to organic solvent and had drunk sodium benzoate), exposed A group (n=24, who were coexposed to toluene and xylene, and had drunk sodium benzoate), and exposed B group (n=21, who were coexposed to toluene and xylene, and had not drunk sodium benzoate). The study methodology consisted of questionnaire survey, urinary analysis for metabolites of toluene and xylene before and after drinking with or without sodium benzoate, and personal air sampling of toluene and xylene. RESULTS: Before drinking, there was no significant difference in UHA or UMHA between the exposed A and B groups. After 1.5 hour of drinking, UHA of the exposed A group was significantly higher than that of the exposed B group. After 3 hours, however, UHA of the exposed A group was decreased to the level of the exposed B group, regardless of the ambient toluene level. UMHA exhibited no significant difference between the exposed A and B groups regardless of time and ambient toluene level. The regression model showed that drinking of sodium benzoate was positively correlated with UHA after 1.5 hours of drinking, but not after 3 hours. In addition, sodium benzoate didn't affect UMHA. CONCLUSIONS: This study showed that sodium benzoate initially increased UHA temporally but that its effect disappeared after 3 hours. In the medical examination of toluene exposure workers, the ingestion of drink containing sodium benzoate should be forbidden during the 3 hours prior to urinary sampling.

A Study on Urinary Excretion of o-Cresol and Hippuric Acid of Workers Daily Exposed to Toluene on Each Day of the Week / 항공우주의학회지

BACKGROUND: The purpose of this study is to find out the relationship between the airborne toluene concentrations and the daily urinary metabolites such as hippuric acid and o-cresol for a sequential 5 days and to provide the appropriate sampling time for a special physical examination in the workers exposed to toluene. METHODS: The volunteers of 36 workers in the shoe making company were selected to measure the concentrations of airborne toluene exposure and to sample the daily urines in pre and end-shift for sequential 5 days form Monday to Friday and to get self-administered questionnaire including the items such as job records, disease records, smoking, alcohol drinking, eating some foods containing benzoic acid before work. RESULTS: The geometric means of toluene concentrations showed 46.40 ppm as the lowest value on Monday and 62.31 ppm as the highest one on Thursday. But there is no significant difference between both of those. The concentrations of hippuric acid and o-cresol in urine sampled on end-shift were higher than that of the others and showed statistically significant differences on each day. The metabolites of toluene were not related with taking alcohol and some foods containing benzoic acid as a result of logistic regression. CONCLUSION: From the above results, it is suggested that the hippuric acid and o-cresol in urine be very useful for biological monitoring in the workers exposed to toluene. Moreover, the daily hippuric acid and o-cresol concentrations in urine are also important for toluene exposure assessment and the further study has to be conducted to find out the tendency of biological exposure indices for continuous toluene exposure.

Effect of Soft Drink on Urinary Hippuric Acid Excretion in Workers Exposed to Low dose Toluene / 대한산업의학회지

OBJECTIVES: To investigate the effect of soft drink containing benzoic acid on the excretion of urinary hippuric acid after ingestion of soft drink containing benzoic acid before working (Edthe deleted section is not an objective). METHODS: Fifty workers (male, 35; female, 15) exposed to toluene in Choongchung province area were studied. Urinary samples were collected on two days. On the first day, all study subjects were required to avoid any soft drink containing benzoic acid for the 24-hour period before urine collection. After emptying their bladder before starting work, the total volume of urine for the full shift period was collected and spot urine was collected at the end of the shift. On the second day, all workers were provided with soft drink containing benzoic acid before the shift and the same urine collection procedure was applied as on the first day. The air concentrations of toluene for each workers was measured with personal air sampling with 3M organic solvent badge. Personal informations such as age, sex, smoking and drinking habit were collected by self-administered questionnaire method. RESULTS: The geometric mean of urinary hippuric acid without ingestion of soft drink containing benzoic acid was 0.49+/-0.45 g/g creatinine in total volume urine, and 0.51+/-0.53 g/g creatinine in spot urine, whereas the equivalent results with ingestion of soft drink were increased to 0.92+/-0.61 g/g and 0.96+/-0.78 g/g, respectively. Stepwise multiple regression of urinary hippuric acid with air concentration of toluene, benzoic acid and other covariates revealed that 49% and 11% of urinary hippuric acid concentration in total volume urine analysis were attributed to the air concentration of toluene and benzoic acid, respectively, compared to 45% and 6% in spot urine analysis, respectively. On the other hand, taking the difference of urinary hippuric acid before and after ingestion of soft drink containing benzoic acid as a dependent variable and taking the air concentration of toluene, benzoic acid and other covariates as independent variables, stepwise multiple regression analysis revealed that 14% and 13% of urinary hippuric acid concentration in total volume urine analysis were attributed to the air concentration of toluene and benzoic acid, respectively, whereas only 9% of urinary hippuric acid concentration in spot urine analysis was attributed to the air concentration of toluene, (Ed- note that there is no respective comparison here). CONCLUSION: Soft drink containing benzoic acid significantly affected the level of urinary hippuric acid after ingestion of soft drink before working. It is recommended that for the accurate elevation of urinary hippuric acid as an index of toluene exposure, detailed information on soft drink containing benzoic acid needs to be checked in the process of the health examination of toluene exposure workers.

Assessment of Neurobehavioral Performance Among Rotogravure Printing Workers Exposed to Toluene / 대한산업의학회지

OBJECTIVES: The aims of this study were to investigate the occupational exposure level to toluene among rotogravure printers and neurobehavioral effects among them. METHODS: Fifty rotogravure printers and 147 controls participated in this study. Environmental and biological monitoring was performed for the investigation of toluene exposure level, and neurobehavioral performance test were performed by using the Behavioral Assessment and Research System with Korean language instructions(BARS-K). RESULTS: The major results were as follows; 1. Geometric mean toluene concentrations in the ambient air of 5 rotogravure printing workplaces were 10.5 (GSD 5.9)~181.9 (GSD 17.7), with a grand total of 56.7 (GSD60.9) ppm. 2. The geometric mean urinary hippuric acid level for rotogravure printers of 5 workplaces were 0.31 (GSD 0.11)~5.14 (GSD 0.55), with the grand total of 1.87 (GSD 2.06) g/g creatinine. 3. There was a linear correlation between hippuric acid levels in urine and the exposed toluene in air: urine hippuric acid (g/g creatinine)=0.03 toluene (ppm) + 0.15 (r=0.899, p<0.01, n=50). 4. After adjustment for confounders, significant associations were found between toluene exposure and Digit span forwards, Digit span backwards, Tapping preferred hand, Symbol digit and Selective attention trials. CONCLUSIONS: 1. Rotogravure printers were occupationally exposed to relatively high concentration to toluene, and their neurobehavioral performances were decreased. 2. The BARS neurobehavioral testing program, which minimizes the use of text in the instructions, was very effective in overcoming the cultural barriers in neurobehavioral testing.

Effects of Respirator Use Evaluated by Urinary Hippuric Acid Concentration in Toluene-Exposed Workers / 대한산업의학회지

OBJECTIVES: This study was carried out in order to raise workers'recognition of the effects of respirator use by providing concrete and practical data. METHODS: Twenty-six workers who dealt with toluene based ink and diluents at a gravure printing office in Seoul were investigated. The toluene exposure level and urinary hippuric acid level were monitored under respirator non-wearing(RNW) and under respiratory wearing(RW) conditions. RESULTS: The mean concentrations of toluene exposed to each worker through the air of gravure printing office were 147.52+/-57.34 and 134.55+/-52.44 ppm on respirator non-wearing day and respirator wearing day, respectively. There was no significant difference in toluene exposure concentration for the two days. The mean concentration of urinary hippuric acid in RNW and RW groups were 1.51 (0.53) g/L and 0.49 (0.14) g/L, respectively, as measured at the end of the workday. There was a significant difference seen in urinary hippuric acid concentration between the two days. The urinary hippuric acid concentration began to increase at 4 hours after the start of the workday(13:00) in RNW. However, there was no significant increase until the end of the workday in the case of RW. The urinary hippuric acid concentration in RW reduced 89.3% as compared with the concentration seen in RNW. There was a significant correlation between the toluene concentration and the urinary hippuric acid concentration in RNW. The regression equation was Y (urinary hippuric acid concentration, g/L) = 0.007 X x(toluene concentration in the air, ppm) + 0.665. CONCLUSIONS: Our results indicate that the respirator intercepted most toluene that may have been absorbed into the respiratory organs, and suggested that properly wearing a respiratory such as wearing the respirator during the entire workday and performing a proper fit test played an important role in the protection from toluene exposure

Effects of Genetic Factor, Life Styles, and Diet on Urinary Hippuric Acid Excretion in Toluene Exposed Workers / 대한산업의학회지

OBJECTIVES: The purpose was to investigate the distributions and the effects of genetic polymorphism of aldehyde dehydrogenase 2(ALDH2), cytochrome P450 1A1(CYP1A1), and cytochrome P450 2E1(CYP2E1) on the toluene metabolism. METHODS: The subjects consisted of 160 workers who were exposed to toluene in different industries such as paint manufacturing, painting on steel and wood products, printing, bonding, and coating. The exposed toluene level was monitored by passive air sampler, and the questionnaire variables were age, sex, smoking, drinking, previous nights drinking, use of personal protective equipment, work duration, and taking benzoic acid containing food. The urinary hippurric acid collected in the end of shift was corrected by urinary creatinine concentration. The genotypes of ALDH2, CYP1A1, and CYP2E1 were investigated using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) methods with DNA extracted from venous blood. RESULTS: The geometric mean and the geometric standard deviation of urinary hippuric acid concentration were 0. 44 g/g creatinine and 2. 80. The urinary hippuric acid concentration was significantly related to personal exposed toluene level among personal exposed toluene level, use of personal protective equipment, and benzoic acid containing food diet. The slope differences of the regression for ALDH2, CYP1A1, and CYP2El genetic polymorphism, age, smoking, and work duration tended to be significant. In multiple regression analysis, the regression coefficient of toluene, ALDH2, CYP1A1, CYP2E1 genetic polymorphism were significant. CONCLUSIONS: Prom the above results, urinary hippuric acid level after toluene exposure was significantly affected by the genetic polymorphism of ALDH2, CYP1A1, CYP2E1. It is needed further investigation of the urinary hippuric acid level considering the effect of genetic polymorphism.

A Study on the Effects of Taking the Drink Containing Benzoic Acid on Analysis of Hippuric Acid in Urine

BACKGROUND: Benzoic acid contained in some food can hinder the biological monitoring of hippuric acid in urine, which is frequently used as an exposure index of toluene and xylene. METHOD: 20 male examinees who are not exposed to organic solvents in their jobs were given a bottle of drink containing benzoic acid(70 mg/dl) and took it. Urine samples were taken from every person just before, in 1.5 hrs after, and in 3 hrs after taking the drink. Hippuric acid in urine was analyzed with improved Ogata and Taguchi method and creatinine with Jaffe method. RESULT: Mean hippuric acid concentrations in urine just before, in 1.5 hrs after, and in 3 hrs after taking the drink were 0.59+/-0.21 g/g creatinine, 2.75+/-0.98 g/g creatinine, 1.04+/-0.58 g/g creatinine, respectively. And, each group had statistically significant differences (p<0.01). There were no statistically significant differences between two groups categorized by age, smoking, and drinking. CONCLUSION: From the results, we suggest that when hippuric acid concentration in urine is used as a exposure index of toluene, it should be surveyed whether the food containing benzoic acid was taken or not.

The Relationship Between Hippuric Acid in Blood Plasma and Toluene Concentration in the Air of Workplace / 예방의학회지

OBJECTIVES: This study was undertaken to evaluate correlation between the levels of hippuric acid in blood plasma (HAP) and those of toluene concentration in the workplace air. METHODS: Study subjects were composed of two groups; 21 workers who were occupationally exposed to toluene and 25 rural-area residents who were not exposed to any known occupational toluene source, as an exposed group and a reference group, respectively. Mean age and work duration of the exposed was 42 years and five years, respectively. Mean age of the reference was 42 years. To determine toluene concentrations in the workplace air, air sampling has been conducted for more than six hours using a personal sampler, and analyzed by a gas chromatography-flame ionization detector. Concentrations of hippuric acid in biological samples were determined by a high performance liquid chromatography-ultraviolet detector. RESULTS: Geometric mean(geometric standard deviation) of HAP and hippuric acid in urine(HAU) for the exposed was 1.39(2.21) mg/L and 2.77(1.46) g/L, respectively, which were significantly different from those of the reference [HAP, 0.45(2.94); HAU, 0.37(0.45)]. Toluene concentration in the workplace air was 86.92(range: 45.18~151.23) ppm. The level of HAP or HAU was significantly correlated (r=0.70 and r=0.63, respectively) with that of toluene in the workplace air. The estimated regression equation was logHAP(mg/L)=-3.60+1.93 log(toluene, ppm) or logHAU(g/L)=-0.85+0.67 log(toluene, ppm). The magnitude of correlation was further enhanced when analyzing relationship between toluene concentrations lower than 100 ppm and its corresponding HAP levels. CONCLUSION: Overall, plasma hippuric acid levels were well correlated with toluene concentrations in the workplace air, and a statistically significant correlation was observed for the samples with toluene concentration lower than 100 ppm.

Urinary hippuric acid excretion by intake of food and drink / 대한산업의학회지

OBJECTIVES: Urinary hippuric acid levels have been usually determined to ' evaluate workers exposed to toluene. Food and drink intake could affect urinary hippuric acid excretion and this study was carried out to investigate what kinds of food and drink would affect urinary hippuric acid excretion. METHODS: The subjects were 136 medical school students. Authors measured urinary hippuric acid levels three times from 10 a. m. to noon; before, one hour after and two hours after food or drink-intake, and they were asked not to eat from the previous night (9 p. m) of testing. We selected six diets (bread and coffee, brown sauce noodle, Korean style meal, noodle, pork'galbi and rice and soybean stew and rice), six fruits (apple, grape, orange, pear, persimmon and plum) and five beverages (Alps-D(R), Demisoda(R), Orange juice(R), Pear juice(R) and Pocari sweat(R)). Analysis of urinary hippuric acid was performed by high performance liquid chromatography. RESULTS: Intake of popular Korean diets, fruits and some drinks didn' t affect urinary hippuric acid excretion. But intake of sodium benzoate-contained Alps-D(R) increased urinary hippuric acid excretion. CONCLUSIONS: For the health examination on workers exposed to toluene, the history of diet and fruit intake can be negligible, but that of beverage intake should be included.

ALDH2 Genetic Polymorphism and Urinary Hippuric Acid Concentration in Toluene Exposed Workers / 대한산업의학회지

In this study we evaluated the effects of the genetic polymorphism of aldehyde dehydrogenase2 (ALDH2) on toluene metabolism and determined biological exposure indices (BEIs) for toluene by the genotypes of ALDH2. The study subject were 77 men workers who are handling toluene in a video tape manufacturing factory and a textile company. Through the face-to-face interview, the information about smoking and drinking behavior wag obtained. For determination of ALDH2 poly morphism, 5 ml of venous blood sample was obtained from each subject after informed consent. DNA was extracted from the buffy coat and ALDH2 genotyping were performed using a polymerase chain reaction (PCR) method. The genotype of ALDH2 was classified into the homozygous genotype of normal ALDH2 (NN), and the heterozygous genotype of normal and inactive ALDH2 (ND), and homozygous genotype of an inactive ALDH2(DD). The concentration of hippuric acid (HA), the main metabolite of toluene, was determined in urine specimens collected at the end of shift, corrected with creatinine (HA/C), and compared with BEI for toluene, which is 2.5 g/g creatinine. The personal exposure level of toluene were monitored, using personal air sampler and analyzed by gas chromatography. The frequencies of the three genotypes in this study subjects were, NN : 45 (58.4%), ND : 26 (33.8%) and DD : 6 (7.8%), and frequencies of the genotypes in the middle or heavy toluene exposure workers were not significantly different from those in the mild toluene exposure workers. The frequencies of the DD type of ALDH2 was lower among alcohol drinkers than among non-drinkers. The urinary HA concentration of DD group was significantly lower than that of the NN or ND group, which suggests that the HA formation from toluene decreased in DD group. Regression lines were used to estimate the BEIs of the NN, ND, and DD groups. NN : y = 0.0085x + 0.23, r = 0.90 ND : y = 0.0074x + 0.21, r = 0.85 DD : y = 0.0041x + 0.82, r = 0.83 The three regression lines revealed that the estimated urinary HA concentration of NN, ND, and DD groups at 377 mg/m3 toluene(TLV-TWA) exposure were 3.43, 3.00, and 2.37 g/g creatinine, respectively. The HA concentration of the NN, and ND group were higher than that of the ACGIH BEI (2.5 g/g creatinine) ; however, the HA level of DD group was lower than the BEI. These results suggests that the ACGIH BEI is not adequate to estimate the toluene exposure of the NN, ND and DD groups at the same time. Based upon those results, a new BEI for ALDH2 deficient workers may be necessary.

Effect of Aldehyde dehydrogenase2 (ALDH2) Genotypes in Urinary Hippuric Acid Excretion as a Biological Exposure Index of Toluene / 대한산업의학회지

We investigated toluene exposure level, urinary hippuric acid concentrations, subjective symptoms and genotype of ALDH2 DNA in 134 exposed workers and 53 nonexposed workers for evaluating the effect of ALDH2 polymorphism on toluene metabolism and urinary hippuric acid concentration as biological exposure indices (BEI) of toluene. The results were as follows; 1. The percentage of inactive genotype of ALDH2 in exposed workers was lower than that of exposed (P=0.081). 2. The percentages of exposed workers with inactive genotype did not have any significant difference by the increase of toluene exposure level or work duration. 3. The frequency of drinking, monthly and maximum amount of alcohol intake in workers with normal genotype were significantly higher than those with inactive genotype. 4. The urinary hippuric acid concentration of nonexposed workers ,with inactive genotype was significantly lower than that with normal genotype. Under 100 ppm of toluene, similar but statistically insignificant trends were found, while above that concentration of toluene, reverse but statistically insignificant trends were found. 5. The number of acute and chronic subjective symptoms were increased positively with the concentration of toluene in workers with normal genotype, but ho such trends were found in workers with inactive genotype. 6. The result of simple linear regression between toluene and urinary hippuric acid concentrations showed a very significant positive linear relation-ship. The mean hippuric acid concentration of nonoccupational exposure was 0.289+/-0.227 (0.062-0.516) g/l. Toluene exposure level unable to discriminate with nonoccupational exposure estimated from regression equation, it range from 7.29 to 9.87 ppm. Considering above all things, it was useful to estimate the exposure level of toluene by means of analysing urinary hippuric acid concentration in both genotype workers, but the biological exposure indices (BEI) of both genotypes were different from each other. The BEI of the total exposed workers was 2.76 g/ I, which was lower than current criteria 3.0g/ I (2.5 g/g Cr), and it also suggest that the BEI for the exposed workers in our country be lowered to the appropriate level after further study.

Effect of Benzoic Acid Containing Foods on the Urinary Hippuric Acid Concentration in Workers Exposed to Toluene / 대한산업의학회지

This Study was performed to investigate the effect of foods containing benzoic acid on the urinary hippuric acid concentration in the toluene exposed workers. The urinary hippuric acid concentration were measured at 0, 30, 60, 90, 120, and 150 minute after intake of soft drink and bread containing benzoic .acid: in volunteers,: who did not have been exposed toluene occupationally. After that urinary hippuric: acids also were measured at the end of shift in toluene exposed workers. And also the concentration of toluene in air were analysed! by gas chromatography. So the relationships between urinary hippuric acid concentration and age, work duration, concentration of toluene in air and intake of benzoic acid containing food were observed. The results were as follows: 1. The urinary hippuric acid concentration reached the highest level at 30 minute after intake of soft drink with bread at a level of 1.41g/g creatinine and soft drink; alone at a level of 1.04g/g creatinine which contained benzoic acid among unexposed toluene, and then gradually decreased. 2. In toluene exposed group no significant effect of general; characteristics siich; as gender, age, work duration, drinking and smoking on urinary: hippuric acid concentration was showed in toluene exposed group. 3. The mean value of urinary hippuric acid concentration of group taking benzoic acid containing foods was significantly higher than that of group not taking. 4. Multiple regression analysis showed that toluene concentration in .air and benzoic acid containing foods were together significantly influence on urinary ; hippuric acid concentration. And the function between variables is Y = 0.014Tpluene +0.489Benzoic acid +0.745 and the contribution rates were 31%. In conclusion, it was suggested that the information on intake of benzoic acid containing foods should be considered in measurement of urinary hippuric acid for the more accurate toluene exposure evaluation.

A Study on the Correlation of Ambient Toluene and Xylene with Biological Monitoring Index / 대한산업의학회지

In order to study the correlation of ambient toluene and xylene exposure with their biological monitoring indices, we measured the concentration of toluene and xylene in the workplace. We also measured their biological monitoring indices of workers from August to November in 1994. The exposed group consisted of 103 male workers and the non-exposed group consisted of 34 male workers. The ambient concentration of toluene was 44.7 +/-55.4 ppm and that of xylene was 2.35+/-2.15 ppm. The urinary concentration of hippuric acid in exposed group was 1.72+/-1.53 g/g creatinine and that of non-exposed group was 0.34+/-0.28 g/g creatinine. The difference was statistically significant between two groups (p0.05). When compensated with urinary creatinine, the correlation coefficient of ambient toluene with urinary hippuric acid and ocresol were 0.63(p=0.0001) and 0.65(p=0.0001), respectively. When compensated with urinary specific gravity, the correlation coefficient of ambient toluene with hippuric acid and ocresol were 0.525 (p=0.0001) and 0.547 (p=0. 0001), respectively. The compensation method using urinary creatinine provided a higher correlation coefficient. We could not find any statistically significant differences between the duration of work and other variables (urinary hippuric acid, o-cresol and methylhippuric acid). In order to monitor biological indices of toluene-exposed workers, we suggest the measurement of urinary hippuric acid rather than o-cresol. As the compensation method, we suggest to use urinary creatinine rather than urinary specific gravity.

Validation of New Derivatization Procedure for the Determination of Hippuric Acid in Urine Using Gas Chromatography / 대한산업의학회지

Urinary hippuric acid was analyzed by gas chromatography/mass spectrometry method. A simple and economical derivatization procedure using excessive methanol in acidic condition was adopted to esterify hippuric acid. Quantitative analysis was performed with two internal standards, heptadecanoic acid and hydrocinnamic acid, to evaluate the derivatization procedure as an analytical method. Using the standard addition method, linear and reproducible calibration curves were obtained for both internal standards. Calibration experiment showed that good quantitative result could also be obtained with the calibration curve obtained without urine matrix. Recovery rates for the urine samples were in the range of 95.6~111.4%. Using hydrocinnamic acid as internal standard, analysis time could be reduced.