Excretion Of Hippuric Acid Research Articles

톨루엔 폭로근로자의 요중 마뇨산 농도 및 건강장해

The relationships between subjective symptoms of toluene exposed workers and concentration of their urinary excretion of hippuric acid were investigated. The exposed groups of 146 workers exposed to toluene and the control groups of 47 workers have never been exposed to toluene in Ulsan area were selected and studied. Hippuric acid was measured by HPLC, and counts of blood cells and liver function test were also performed. The mean value of urinary hippuric acid concentration of the control group was 0.322(<TEX>$\pm$</TEX>0.267) g/L, while that of the exposed group was 1.260(<TEX>$\pm$</TEX>0.395) g/L. As the concentration of hippuric acid had statistical proximity in <TEX>$0.1\%$</TEX> level, WBC, GOT, and GPT didn't have any proximity(P>0.05). The exposed group showed lower level of leucocyte counts 6522.40(1710.3) than the control group 6891.50(1483.7). The exposed group showed higher level of GOT(25.75), GPT(27.09) than GOT(23.75), GPT(25.21) of the control group. Dried skin was the highest complained symptom of toluene exposed workers, the second strained eye, the third poor auditory function, and the fourth was headache.

Toxicology and carcinogenesis studies of microencapsulated trans-cinnamaldehyde in rats and mice

trans-Cinnamaldehyde is a widely used natural ingredient that is added to foods and cosmetics as a flavoring and fragrance agent. Male and female F344/N rats and B6C3F 1 mice were exposed to microencapsulated trans-cinnamaldehyde in the feed for three months or two years. All studies included untreated and vehicle control groups. In the three-month studies, rats and mice were given diets containing 4100, 8200, 16,500, or 33,000 ppm trans-cinnamaldehyde. In rats, feed consumption was reduced in all exposed groups. In mice, feed consumption was reduced in the highest dose groups. Body weights of all treated males were less than controls. Body weights were reduced in female rats exposed to 16,500 or 33,000 ppm and female mice exposed to 8200 ppm or greater. All rats survived to the end of the study but some male mice in the highest dose groups died due to inanition from unpalatability of the dosed feed. The incidence of squamous epithelial hyperplasia of the forestomach was significantly increased in rats exposed to 8200 ppm or greater and female mice exposed to 33,000 ppm. In mice, the incidence of olfactory epithelial degeneration of the nasal cavity was significantly increased in males and females exposed to 16,500 ppm and females exposed to 33,000 ppm. In the two-year studies, rats and mice were exposed to 1000, 2100, or 4100 ppm trans-cinnamaldehyde. Body weights were reduced in mice exposed to 2100 ppm and in rats and mice exposed to 4100 ppm. In rats, hippuric acid excretion was dose proportional indicating that absorption, metabolism, and excretion were not saturated. No neoplasms were attributed to trans-cinnamaldehyde in rats or mice. Squamous cell papillomas and carcinomas of the forestomach were observed in male and female mice but the incidences were within the NTP historical control range and were not considered to be related to trans-cinnamaldehyde exposure.

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

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

Assessment of DNA damage in glue sniffers by use of the alkaline comet assay

Toluene is used widely, not only in industry, but also in households where toluene exposure and abuse can occur. To estimate the genotoxic risk of toluene exposure, DNA damage was determined in peripheral lymphocytes of 20 glue sniffers and 20 age-matched controls by use of the alkaline comet assay. Urinary hippuric acid and o-cresol excretion rates, which are used as a marker for toluene exposure, were also measured in sniffers and compared with historical control values. The increase in genetic damage in sniffers was statistically significant as compared to control subjects ( P<0.0001). The mean values of the hippuric acid and o-cresol excretion rate for glue sniffers was 73- and 1582-fold higher, respectively, than in controls and confirms the putative exposure. Education of the general public and efforts to keep adolescents away from volatile solvent-based products, which may lead to a desire of sniffing in the future, would be advisable.

Detoxification in relation to toxin tolerance in desert woodrats eating creosote bush.

We studied the relationship between the use of three detoxification pathways and urine pH and the tolerance of desert woodrats from two populations to a mixture of naturally occurring plant secondary metabolites (mostly phenolics) in resin from creosote bush (Larrea tridentata). The two populations of desert woodrats came from the Mojave desert (Mojave woodrats), where woodrats consume creosote bush, and from the Great Basin desert (Great Basin woodrats), where the plant species is absent. We fed woodrats alfalfa pellets containing increasing levels of the phenolic resin and measured three detoxification pathways and urine pH that are related to detoxification of allelochemicals. We found that the excretion rate of two phase II detoxification conjugates, glucuronides and sulfides. increased with increasing resin intake, whereas excretion of hippuric acid was independent of resin intake, although it differed between populations. Urine pH declined with increasing resin ingestion. The molar proportion of glucuronides in urine was three times that of the other conjugates combined. Based on an evaluation of variation in the three detoxification pathways and urine pH in relation to resin intake, we rejected the hypotheses that woodrats' tolerance to resin intake is related to capacity for amination, sulfation, or pH regulation. However, Mojave woodrats had higher maximum glucuronide excretion rates, and we accepted the hypothesis that within and between populations woodrats tolerate more resin because they have a greater capacity for glucuronide excretion.

Urinary Excretion of Hippuric Acid after Consumption of Nonalcoholic Beverages

To investigate the types and quantities of beverages that increase urinary hippuric acid (HA) excretion, the authors recruited 137 healthy medical students and divided them into quintiles according to consumption of benzoic acid (BA) in beverages. Using chromatography, urinary HA before and 1.5 hours and 3 hours after consumption of various beverages and BA consumption in the beverages were measured. The mean age of the group was 24.2 years; 21 were female. The range of BA in 13 beverages was 0-1.02 mg/mL. The geometric means of urinary HA before consuming them in five groups were 0.276, 0.270, 0.207, 0.262, and 0.316 g/L, respectively (p = 0. 567); 1.5 hours after consuming the beverages, they were 0.210, 0. 603, 1.026, 1.066, and 1.688 g/L, respectively, and significantly increased after adjustment for urinary HA before ingestion (p < 0. 001). Three hours after ingestion, the geometric means were 0.160, 0. 232, 0.306, 0.287, and 0.337 g/L, respectively (p < 0.001). The authors estimate that beverages that contain more than 100 mg BA could increase urinary HA excretion significantly, up to 1.12 g/L without toluene exposure. Checking dietary and beverage-intake histories is essential in the interpretation of urinary HA concentrations in population studies.

Effect of dietary glycine and benzoate level on benzoate metabolism in mink (Mustela vision), blue fox (Alopex lagopus), and raccoon dog (Nyctereutes procyonoides).

Three 2 x 4 factorial experiments were carried out from August to September with 30 juvenile male mink, 24 raccoon dogs, and 24 blue foxes to investigate the effect of dietary glycine supply (low or high) on the efficiency of these species to excrete hippuric acid with incremental benzoate intake (0, 1, 2, or 4 mmol/kg BW). For mink, two additional treatments with 1 or 2 mmol/kg BW of ethyl benzoate were included. A basal low-glycine diet was formulated to meet the minimum protein requirements of fur animals (30% of ME). This diet was supplemented with 0 or 3 g/kg of glycine, or with 0, 1.0, 2.07, or 4.15 g/kg of sodium benzoate for mink and blue foxes, and with 0 or 4.5 g/kg of glycine and 0, 1.58, 3.17, or 6.34 g/kg of sodium benzoate for raccoon dogs, respectively. Two additional diets with .76 or 1.53 g/kg of ethyl benzoate were made for mink. Fecal and urinary benzoic and hippuric acid excretion were measured for 3 d. The 24-h recovery of [14C]benzoic acid injected intraperitoneally was measured from urine, the liver, and the kidneys. All animals appeared healthy and no clinical signs of benzoate overdose were observed. Dietary benzoate level did not affect ADFI or ADG in any species. Glycine supplementation lowered ADFI in mink. The majority of ingested benzoates were absorbed from the gut (over 95%), except in blue foxes, which excreted 6 to 15% of ingested benzoates in feces with incremental increases in benzoate intake. Urinary free benzoic acid excretion accounted for 10% of the ingested benzoates in blue foxes but less than 5% in mink and raccoon dogs. When benzoate intake was 1 mmol/kg BW, mink, blue foxes, and raccoon dogs excreted 71, 77, and 34% of ingested benzoates as hippuric acid in urine, respectively. With higher benzoate intakes, urinary hippuric acid excretion decreased quadratically with mink to 20%, and linearly with blue foxes and raccoon dogs to 45 and 16%, respectively. The hippuric acid pathway appears to be the principal route of benzoate elimination in the mink and blue fox, whereas, in the raccoon dog, other pathways appear to be more important. In mink, the elimination of ethyl benzoate did not differ from that of sodium benzoate. Because glycine conjugation is the primary route of benzoate elimination, it is recommended that benzoate content in fur animal feeds should not exceed 1 g/kg feed on an as-fed basis.

Hippuric acid as a major excretion product associated with black tea consumption

1. Nine habitual tea-drinking volunteers were recruited and asked to follow a low-polyphenol and low-caffeine diet for 6 days and to provide daily 24-h urine samples. On day 4 of the experiment strong black tea brewed under standardized conditions was reintroduced to the volunteers' diet. 2. 1H-NMR and HPLC profiling of the urine samples indicated that consumption of black tea (6-10 mugs per day) was associated with a significant (p=0.00017) increase in hippuric acid excretion relative to control, increasing from 153-512 to 742-1374 mg day-1. The excretion of substantial amounts of hippuric acid has not previously been associated with black tea consumption. 3. For some volunteers, the quantity of benzoic acid processed exceeded the acceptable daily intake (ADI), but this is not considered to constitute any hazard. 4. A mass-balance analysis indicated that the necessary quantity of benzoic acid could not be obtained from the contents of gallic acid, flavanols, flavonol glycosides and theaflavins in black tea even if 100% transformation was obtained, suggesting that the thearubigins (the major and chemically ill-defined polyphenols of black tea) may be an important source.

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

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

Possible Effects of Drinking and Smoking Habits on Hippuric Acid Levels in Urine of Adults with No Occupational Toluene Exposure

Drinking and Smoking Habits and Urinary Level of Hippuric Acid in Adults not Exposed to Toluene: Edna Maria Alvarez‐leite, et al. Department of Clinical Chemistry and Toxicology, College of Pharmacy, Federal University of Minas Gerais‐UFMG, Brazil—Hippuric acid (HA) is still the biomarker most used for monitoring exposure to toluene, but it is produced by the body even in the absence of this solvent, and has the disadvantage of showing significant variation in and between individuals, depending on environmental factors and individual characteristics. A number of studies have reported the influence of individual drinking and smoking habits on toluene metabolism, but the effect on urinary excretion of HA is still controversial. This study was conducted in an attempt to examine whether these individual habits also affect HA excretion in individuals not exposed to toluene. Urine sample from 195 people (99 women and 96 men), ranging in age from 17 to 46 years old, were collected. The individuals were classified in groups according their drinking and smoking habits. The data from the current study indicate that these two social habits, either separately or combined, do not influence basal urinary HA levels in this study group.

Urinary hippuric acid excretion by intake of food and drink

Urinary hippuric acid excretion by intake of food and drink

Occupational Exposure to Low Concentrations of Organic Solvents in Shipyards

Occupational Exposure to Low Concentrations of Organic Solvents in Shipyards: Hironobu Katsuyama, et al. Department of Public Health, Kawasaki Medical School—Because shipbuilders have to use organic solvents in very confined spaces, they have a higher risk of inhaling the solvents than workers working in an open space. The working environment at 14 workplaces with very limited space was examined and biological monitoring was performed on 18 workers who worked in such places. Out of 14 workplaces, only 4 did not exceed the assessment criterion. Although exhaust ventilation fans and chemical cartridge respirators were used to avoid exposure to solvent vapor irrespective of the concentrations of solvents, biological samples revealed inhalation of solvent vapor. Urinary excretion of hippuric acid and methylhippuric acid varied from 0.07 to 0.92 g/ g Cr and 0.02 to 0.42 g/g Cr at the end of the shift, respectively. Concentration of toluene and xylene in the end‐exhaled air varied from &lt;0.1 to 5.0 ppm and &lt;0.1 to 10.6 ppm, respectively. The concentration of metabolites in urine and the concentration of solvent in the end‐exhaled air revealed a strong correlation in the case of xylene but not toluene. Because of the limitation of space, the mean concentration of solvents in the working environment is not always available in shipyards, which make it difficult to estimate the amounts inhaled by workers. Biological monitoring of the end‐exhaled air provides useful information to make it possible to avoid continuous and/or unexpected exposure of workers who have to work in a very limited space.

Sister chromatid exchanges in rotogravure printing plant workers.

The individual burden of inhaled ambient-air toluene and its link to genotoxic phenomena in exposed printing workers. The influence of toluene on sister chromatid exchange (SCE) was investigated by monitoring of the individual toluene burden of 42 exposed printing workers. Therefore, the urinary hippuric acid (HA) excretion was measured directly after the work shift. The results were compared with those recorded for a control group consisting of 45 blood donors. SCE frequencies were determined from peripheral lymphocytes for both groups. The median HA excretion of the exposed and nonexposed groups amounted to 1.94 and 0.45 g/g creatinine, respectively. For both groups, different SCE rates were detected: 10.13 and 6.84 counts/lymphocyte for exposed and nonexposed persons, respectively. The independence of the measured values proved to be significant at a high confidence level (P = 0.000) for both groups. The influences of smoking and alcohol consumption on SCE as well as on HA values could be clearly separated from those induced by toluene. The results of our study indicate a strong relationship between the individual toluene burden and the genotoxic risk of the exposed persons. Since toluene was used for dilution of the letter-press ink, the influence of ink mist on the genotoxic effects could not be completely excluded.

周期性四肢麻ひを反復したトルエン中毒による尿細管性アシドーシスの１例

A 25-year-old man with a history of toluene sniffing was admitted to the hospital because of tetraparesis. Laboratory examination revealed severe hypopotassemia, hyperchloremia, metabolic acidosis with a normal anion gap, elevation of serum GOT, GPT, CK, and alkaluria, and incresed urinary excretion of hippuric acid. Alkaluria despite metabolic acidosis and severely decreased serum bicarbonate were consistent with distal renal tubular acidosis. Increased urinary excretion of hippuric acid indicated exposure to toluene, and these findings were highly suggestive of toluene-induced renal tubular acidosis. He gradually recovered with abstinense from toluene sniffing and oral supplement with potassium and bicarbonate.

Effect of diet on the urinary excretion of hippuric acid and other dietary-derived aromatics in rat. A complex interaction between diet, gut microflora and substrate specificity

1. A combined in vivo and in vitro study has been devised to investigate an observation, obtained by 1H NMR of urine, that AlpfAp SD (Wistar derived) rats kept under standard husbandry conditions did not excrete urinary hippuric acid (HA). meta-(hydroxyphenyl)propionic acid {m-HPPA} was identified as the major aromatic component inurine samples lacking HA. 2. Examination of urine from Alp:APfSD and Zücker (obese negative) rats fed various diets showed that the lack of HA/presence of m-HPPA was due to diet and not to the strain of animal.This observation was reinforced by the demonstration that the administration of benzoic acid (BA) to rats not previously excreting urinary HA resulted in the return of this component to the urinary excretion profile. Thus rats receiving the standard diet were still capable of glycine conjugation. 3. Changing the diet of rats excreting m -HPPA led to the cessation of m-HPPA excretion and the return of HA urine excretion. Interestingly, switching back to the original diet did not cause the loss of HA and the re-emergence of m-HPPA. 4. In vitro studies on the two enzyme systems responsible for glycine conjugation (benzoyl CoA:synthetase and benzoyl CoA:glycine N-acyltransferase) in isolated liver mitochondria showed that m-HPPA did not inhibit either enzyme. However, m-HPPA was not found to be a substrate for the first reaction step explaining why it was found in the urine as the free acid and not as a glycine conjugate. 5. The absence and presence of m-HPPA and hippuric acid is suggested to be due to a combination of differences in dietary precursors of substrates for glycine conjugation and a dietary dependent redistribution of theintestinalmicroflora responsible for breakdownof plant phenolics and aromatic amino acids. Taken collectively this study emphasises how a simple diet change can cause a profound change in metabolism.

Excretion of benzoic acid derivatives in urine of sheep given intraruminal infusions of 3-phenylpropionic and cyclohexanecarboxylic acids.

The quantitative relationship between the urinary excretion of benzoic acid (BA) and the uptake of 3-phenylpropionic (PPA) and cyclohexanecarboxylic (CHCA) acids was assessed. PPA and CHCA are produced in the rumen by microbial fermentation of lignocellulosic feeds and metabolized, after absorption, to BA which is excreted in the urine mainly as its glycine conjugate hippuric acid (HA). Four sheep nourished by intragastric infusions of all nutrients were given continuous ruminal infusions of PPA (8, 16 or 24 mmol/d) either alone or with CHCA (8 or 16 mmol/d) in a factorial experiment. The treatments were allocated to ten consecutive 6 d periods, with a control being repeated at periods 1, 5 and 10. PPA and CHCA ruminal absorption rates, estimated using the liquid-phase marker Cr-EDTA, were 0.78 (SD 0.29)/h and 0.88 (SD 0.28)/h respectively. For the control, HA excretion was only 0.22 (SD 0.33) mmol/d and free BA was absent. For the other treatments, both HA and free BA were present and HA accounted for 0.85 (SD 0.05) of total BA: The urinary excretion of total BA showed a significant linear correlation (r = 0.997, P < 0.001) with the amounts of PPA and CHCA infused. The urinary recovery of infused PPA and CHCA as total BA was 0.79 (SE 0.01). Faecal excretion of BA and its precursors was negligible. Results of this study show that urinary total BA is a potential estimator of the absorption of PPA + CHCA produced in the rumen.

Urinary excretion of benzoic acid and hippuric acid in sheep given ruminal infusion of 3-phenylpropionic and cyclohexanecarboxylic acids

Microbial fermentation of lignoceluUosic feeds in the rumen produces 3-phenylpropionic (PPA) and cyclohexanecarboxylic (CHCA) acids. Feed phenolic cinnamic acids are regarded as the main precursors of PPA upon microbial action (Martin 1982b). CHCA can be produced by microbial metabolism of dietary alicyclic compounds such as quinic and shikimic acids (Balba and Evans, 1977; Martin, 1982a). Following absorption CHCA and PPA are subjected to metabolism mainly in the liver yielding benzoic acid (BA) which is extensively excreted in urine mainly as its glycine conjugate hippuric acid (HA). The aim of this work was to assess the quantitative relationship between the urinary excretion of total BA (free BA + HA) and the uptake of PPA and CHCA.

Urinary excretion of benzoic acid and hippuric acid in sheep given ruminal infusion of 3-phenylpropionic and cyclohexanecarboxylic acids

Microbial fermentation of lignoceluUosic feeds in the rumen produces 3-phenylpropionic (PPA) and cyclohexanecarboxylic (CHCA) acids. Feed phenolic cinnamic acids are regarded as the main precursors of PPA upon microbial action (Martin 1982b). CHCA can be produced by microbial metabolism of dietary alicyclic compounds such as quinic and shikimic acids (Balba and Evans, 1977; Martin, 1982a). Following absorption CHCA and PPA are subjected to metabolism mainly in the liver yielding benzoic acid (BA) which is extensively excreted in urine mainly as its glycine conjugate hippuric acid (HA). The aim of this work was to assess the quantitative relationship between the urinary excretion of total BA (free BA + HA) and the uptake of PPA and CHCA.

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

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

Dose-dependent suppression of toluene metabolism by isopropyl alcohol and methyl ethyl ketone after experimental exposure of rats

In order to examine possible suppression of toluene metabolism due to coexposure to other solvents, female Wistar rats were exposed for 8 h to toluene alone (at 50 or 100 ppm), or in combination with either methyl ethyl ketone (at 50, 100, 200 or 400 ppm) or isopropyl alcohol (at 50, 100, 200, 400, 800 or 1600 ppm). Urine samples were collected for 24 h after initiation of each exposure, and subjected to analysis for two toluene metabolites, hippuric acid and o-cresol, both by HPLC. The excretion of hippuric acid, a major metabolite, was not modified when the concentrations of methyl ethyl ketone or isopropyl alcohol were low, i.e. 100 ppm or below, whereas it was reduced when methyl ethyl ketone or isopropyl alcohol concentrations were twice or more times higher than that of toluene. There were no changes in any cases in excretion of o-cresol, a minor metabolite. The observation after coexposure to methyl ethyl ketone or isopropyl alcohol at low concentration is in line with the negative interaction between toluene and methyl ethyl ketone as well as between toluene and isopropyl alcohol after occupational exposures at low concentrations. Metabolic interaction may take place when the exposure intensity is high, as observed in the present study and also after experimental exposure of volunteers to toluene and m-xylene, or occupational exposure to benzene and toluene.