Analysis of urinary S-phenylmercapturic acid and trans, trans-muconic acid as exposure biomarkers of benzene in petrochemical and industrial areas of Korea

OBJECTIVES: Recently, S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA) in urine have been proposed as reliable biomarkers for monitoring occupational exposure to benzene. The aim of this study was to test the applicability of S-PMA and t,t-MA as exposure biomarkers and to monitor the occupational exposure level and the extent of environmental contamination from benzene in Korea. METHODS: The urinary excretion of S-PMA and t,t-MA in rats after the intraperitoneal administration of benzene (0.88-800 mg/kg body weight, 7 days) was examined. These biomarkers were also validated in human urine samples collected from elementary schoolchildren in several industrial areas including chemical manufacturing plants, oil refineries, and natural gas-producing installations in Korea. Urine was collected from elementary schoolchildren in a mountain village with no known occupational exposure to benzene and air pollution as the reference group. RESULTS: In rats, there was a significant relationship between the benzene concentration and the excretion of the urinary S-PMA and t,t-MA as a function of concentration, and the excretion of benzene metabolites peaked on the first day after intraperitoneal administration. In human urine, higher levels of S-PMA and t,t-MA were detected more frequently in petrochemical industrial areas than in areas with no known occupational exposure to benzene. CONCLUSIONS: These results show that the quantitative determination of S-PMA and t,t-MA in urine can be used as a reliable exposure biomarker for benzene, and they also suggest that extensive attention to benzene exposure is needed for maintaining the health of the population in Korea.     

Soil adsorption alters kinetics and bioavailability of benzene in orally exposed male rats

A study comparing the bioavailability of pure vs soil-adsorbed benzene was conducted in adult, male rats. Animals were gavaged with an aqueous suspension of benzene alone or adsorbed to either a Keyport series (clay soil) or a Cohansey aquifer solid (sandy soil) from New Jersey. Peak plasma concentration of radioactivity was increased in the presence of either soil vs benzene alone while the sandy soil also decreased the time to reach peak vs benzene alone. Either soil produced an increase in the area under the plasma radioactivity-time curve versus benzene alone, while the clay soil did so in a statistically significant manner. The half-life (t_1/2) of absorption into plasma was not statistically different in the presence of either soil, while each soil decreased the t_1/2 of elimination vs benzene alone and clay soil did so in a statistically significant manner.Two hr after exposure, stomach tissue contained the highest amount of radioactivity followed by fat in all treatment groups. No differences were detected in the tissue concentration of radioactivity between the treatment groups.Expired air was the primary excretion route following exposure to benzene alone with lesser amounts of radioactivity eliminated in the urine during the 48 hr following exposure. The opposite pattern was detected in the presence of clay soil, while expired air and urine represented approximately equal routes of excretion in the presence of sandy soil. Unmetabolized benzene represented the bulk of total radioactivity in the expired air of all treatment groups with [¹⁴C]O₂ comprising the remainder. Less than 2% of radioactivity was eliminated by the fecal route for all treatments with significantly higher amounts in the clay soil treatment versus benzene alone.Phenol was the primary benzene metabolite detected in the 0–12 hr urines of all treatment groups. Lesser amounts of hydroquinone, catechol, and benzenetriol were also detected. No differences in the metabolite percentages were detected between the treatment groups.     

苯DNA加合物的形成特征,条件和方法探讨

为进一步探讨苯ＤＮＡ加合物的形成特征，稳定地检测苯ＤＮＡ加合物，采用３２Ｐ－后标记法对染苯小鼠体内ＤＮＡ加合物的形成特征及影响因素进行了研究。结果表明：加合物种类与染苯天数有关：５００ｍｇ／ｋｇ染苯５天组外周血白细胞可检出２个ＤＮＡ加合物斑点，而７天组可检出３个主要的和至少１个微弱的加合物斑点；染苯达一定剂量后，加合物含量和种类不再增加，１０００ｍｇ／ｋｇ与５００ｍｇ／ｋｇ染苯７天组的检测结果基本相同；苯醌可能是苯形成ＤＮＡ加合物的主要代谢产物，２．５ｍｇ／ｋｇ苯醌染毒５天的小鼠白细胞中可检出３个主要的及２个微弱的加合物斑点，其层析特性与染苯小鼠加合物的层析性质基本一致。提示：动物染苯天数及次数、层析点样量及层析时间对加合物斑点形成均有影响。     

Muconic acid determinations in urine as a biological exposure index for workers occupationally exposed to benzene.

Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure, but the same technique cannot be used to monitor low-level exposures because of the high background of phenol resulting from its presence in many foods and from metabolism of aromatic amino acids. Thus, new biological indexes for exposure to low levels of benzene are needed. Animal studies indicate that muconic acid is a metabolite of benzene that is excreted in the urine as an increasing fraction of the total benzene metabolites with decreasing dose of benzene. Thus, urinary muconic acid is potentially useful as a monitor for low levels of exposure to benzene. It is also of interest to determine the level of muconic acid in the urine of humans exposed to benzene for comparison with animal data as an aid for use of the animal studies in risk assessments for humans. This report describes the development of a gas chromatography/mass spectrometry assay to detect and quantitate the benzene metabolite, muconic acid, in urine. The internal standard used in the assay, muconic acid-d4, was biosynthesized by F344/N rats administered benzene-d6 by gavage; the muconic acid was isolated from the rat's urine. Muconic acid was measured in experimental urine samples by adding the internal standard, followed by extraction and derivatization. Phenol was also measured in urine after extraction and derivatization. The assays were applied to the urine samples from 14 workers occupationally exposed to benzene and 8 workers with no known benzene exposure. Muconic acid could be detected in all of the urine samples at levels greater than 100 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose-response relations in urinary excretion of trimethylselenonium in the rat

75Se-labeled selenite was administered to fasting rats by orogastric intubation (1.5-3000 micrograms/kg body wt). Urine was collected and characterized for total radioactivity as well as for radiolabeled trimethylselenonium (TMSe). At lower doses of selenite (up to 500 micrograms/kg body wt), 30% of the administered dose was excreted. At higher doses of selenite, fractional urine excretion decreased as a function of the dose. The observed decrease in fractional urine excretion was not caused by changes in the absorption of the administered radiolabel. There was a direct relationship between the amount of the administered dose of selenite (up to 1500 micrograms/kg body wt) and the proportion of urinary [75Se] excreted as TMSe. Pretreatment with seleno compounds (10 or 100 micrograms Se/kg body wt as selenite, or selenomethionine) for 35 d before a challenge dose of [75Se]selenite did not influence the excretion of total [75Se] or of [75Se]TMSe in urine. Ingestion of a choline-deficient diet, which should deplete the availability of methyl groups, did not have any effect on excretion of total [75Se] or of [75Se]TMSe in urine after a challenge dose of [75Se]selenite (500 micrograms/kg body wt). The data presented here permit the following conclusions: 1) Production of TMSe is dose dependent, 2) production of TMSe from a single acute dose does not depend on the history of selenium intake and 3) rats fed a methyl-deficient diet are able to eliminate Se via formation of TMSe.     

Vitamin B-6 deficiency and renal function and structure in chronically uremic rats

In preliminary studies, rats with chronic renal failure (CRF) demonstrated worsening renal function, as measured by urea clearance, when fed vitamin B-6-deficient diets. However, urea clearance is not a precise measure of glomerular filtration rate (GFR) and these studies did not indicate the mechanism for the reduced GFR. To measure renal function more precisely and to assess whether B-6 deficiency augments renal injury, we examined [14C]inulin clearance, urine oxalate excretion, and renal histopathology in rats with CRF pair fed to receive a pyridoxine-replete or -deficient diet for 3 or 6 wk. After 3 or 6 wk, pyridoxine-deficient rats had significantly lower [14C]inulin clearances and increased urine oxalate excretion. Histological evaluation indicated increased renal damage in kidneys from pyridoxine-deficient rats as compared with tissue from pyridoxine-replete rats. These findings suggest that in rats with CRF, vitamin B-6 deficiency reduces the GFR and increases renal scarring.     

Effect of dietary fiber on the disposition and excretion of a food carcinogen (2-14C-labeled MeIQx) in rats.

We studied to what extent dietary fiber may affect uptake, retention, and excretion of a food carcinogen (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, MeIQx) occurring in fried meat. Four diets--one fiber-free control and three containing either insoluble dietary fiber isolated from sorghum (100 g/kg) and wheat bran (100 g/kg) or the highly soluble pectin (50 g/kg)--were investigated. The fiber diets were given in amounts of 10 g/day to rats. Thus, each rat received 1 or 0.5 g fiber and 100 micrograms 2-14C-labeled MeIQx uniformly mixed in its daily diet. A 4-day adaptation period with unlabeled MeIQx was followed by a 5-day experimental period with 14C-labeled MeIQx, during which urine and feces were collected separately for analysis of radioactivity and mutagenicity. Furthermore the composition and the fermentability of the dietary fiber were determined. The present study shows that a diet containing fiber, especially fiber isolated from sorghum and wheat bran, affects the excretion pattern of the food carcinogen MeIQx in a manner suggesting a lower uptake and a decreased transit time through the gastrointestinal tract in a more diluted form than a nonfiber diet. Furthermore, less radioactivity was retained in the kidneys with sorghum and wheat bran than with the other two diets. On the other hand, none of these types of dietary fiber affected the retention of the hepatocarcinogen MeIQx in the liver 24 hours after the last oral intake. DNA adducts were formed to a higher extent in the kidney than in the liver. The highest levels were found in animals given the wheat bran diet.     

Effect of nicotinamide intake on urinary excretion of N1-methylnicotinamide and oxidation of [7a-14C]tryptophan in the rat

Oxidation of tryptophan and urinary excretion of N1-methylnicotinamide were studied in weanling rats fed ad libitum for 10 days 12% casein diets containing from 0 to 500 mg of nicotinamide per kilogram of diet. N1-methylnicotinamide was measured in urine collected during the last 3 days of the experiment. After the feeding period, rats fed the niacin-free and 500 mg nicotinamide diets were placed in metabolic cages, and each rat was given 4 g (dry weight) of diet containing a tracer dose of DL-[7a-14C]tryptophan. Expired CO2 was collected hourly for 10 hours. From rats consuming levels of nicotinamide ranging between 20 and 150 mg/kg of diet, N1-methylnicotinamide excretion increased linearly with increasing nicotinamide intake. From these results and others from this laboratory (4), it was calculated that an additional 10--11 mg of dietary tryptophan above the approximately 20 mg/day essential for growth are needed by the growing rat for the formation of 1 mg of nicotinamide. The addition of 500 mg of nicotinamide per kilogram of diet to a niacin-free diet had no effect on the oxidation of DL-[7a-14C]tryptophan.     

Folic acid, 5-methyl-tetrahydrofolate and 5-formyl-tetrahydrofolate exhibit equivalent intestinal absorption, metabolism and in vivo kinetics in rats.

The intestinal absorption and in vivo kinetics of (6S)-[3H]-5-methyl-tetrahydrofolate (5-methyl-H4folate), (6S)-[3H]-5-formyl-H4folate and [3H]folic acid were investigated to determine whether inherent differences exist in the overall bioavailability of these folates in rats. Adult rats (n = 9 per group) were given an intragastric dose of the appropriate folate (50 pmol/100 g body wt) in 50 mmol/L ascorbate (pH 7). Each compound underwent nearly complete absorption within 8 h, and there was no significant difference in the excretion kinetics in relation to the form of folate administered. A biphasic pattern of excretion was observed over the following 8 d. Both urine and feces were important excretory routes. The rapid phase of total isotopic excretion (urinary and fecal) exhibited a half time (t1/2) of 0.11-0.12 d, whereas the t1/2 of the slower phase was 13.4-15.9 d. Isotopic distributions and the pattern of labeled folates in urine and tissues were similar regardless of the form administered. These results indicate that the bioavailability of orally administered folic acid, 5-methyl-H4folate and 5-formyl-H4folate is equivalent in rats under the conditions of this study.     

Metabolism and disposition of erythritol after oral administration to rats.

The metabolism and disposition of erythritol was studied using [14C]erythritol in rats. When [14C]erythritol was administered orally at a dose of 0.1 g/kg body wt to male rats, only 6% of the total radioactivity was excreted as expired 14CO2 and 88% was excreted in the urine within 24 h. The excreted metabolite in the urine consisted of a single component identified as intact [14C]erythritol. The excretion of 14CO2 and the incorporation ratios of radioactivity into tissues increased with the oral dosage. After rats were given an intravenous injection of [14C]erythritol, approximately 1% was excreted as 14CO2 and greater than 94% was excreted in the urine as intact [14C]erythritol. The excretion of 14CO2 within 24 h was increased to approximately 10% when [14C]erythritol was administered to rats that had been adapted to erythritol by feeding a diet containing 10% erythritol for 2 wk. When [14C]erythritol was incubated in vitro with the cecal contents from rats adapted to erythritol, greater than 20% was fermented to 14CO2 and 60% to short-chain fatty acids in 6 h. These results indicate that most orally administered erythritol was excreted in the urine without any degradation and that the remainder was transferred to the lower intestine and fermented by microbes.     

Determination of Polycyclic Aromatic Hydrocarbons (PAH) and Their Metabolites in Blood, Feces, and Urine of Rats Orally Exposed to PAH Contaminated Soils

Polycyclic aromatic hydrocarbons (PAH) have become an ubiquitous upper soil component as a consequence of industrialization involving a multitude of combustion processes. Ingestion of PAH contaminated soil is considered to be a major exposure route, specifically for small children living on these soils. Health risk assessment is based on extrapolations from data obtained via studies performed with pure chemicals. Additionally it is assumed that after oral intake all PAH present in the soil will be absorbed by the human body. Interactions with the soil matrix, however, may modulate the bioavailability of PAH. In this study, we examined the absorption and excretion of PAH in rats orally exposed either to industrially contaminated soils or pure model compounds as anthracene, pyrene and benzo(a)pyrene (B[a]P). The model compounds and the metabolites, 1-hydroxypyrene (1-OH-pyrene) and 3-hydroxybenzo(a)pyrene (3-OH-B[a]P), were measured in blood, feces or urine by means of HPLC with fluorescence detection. Because of rapid biotransformation only minimal levels of unmetabolized anthracene, pyrene and B[a]P in blood could be detected. The pharmacokinetic parameters were nonlinear and suggestive of enterohepatic cycling. Only low levels of the compounds were excreted unchanged in feces whereas the levels of the metabolites were considerably higher in feces and urine. These results indicate that the dosed PAH are largely absorbed by the gastrointestinal tract, subsequently metabolized and excreted as metabolites via urine and feces. Significant differences between the soil-treated group and the pure mixture-treated group could be observed; the soil-treated group showed higher fecal excretion of unchanged pyrene (0.5 versus 0.2% of the original dose) and B[a]P (1 versus 0.3%), lower excretion of 1-OH-pyrene in feces (5.1 versus 17.0%), and lower excretion of 1-OH-pyrene in urine (0.2 versus 3.4%). The fecal excretion of 3-OH-B[a]P between the two groups was similar (8.8 versus 8.8%). These results suggest that the soil matrix is capable of reducing the absorption of at least pyrene. Therefore, exposure risk assessment models assuming complete bioavailability of soilmatrix-bound PAH probably overestimate the endogenous dose. Received: 18 April 1996/Accepted: 27 March 1997     

Determination of haemoglobin adducts of acrylamide and glycidamide in smoking and non-smoking persons of the general population

Acrylamide (AA) is a food-borne toxicant suspected to be carcinogenic to humans. It is formed in the heating process of starch-containing food. Currently, there is a great discussion about the possible human health risks connected with the dietary uptake of acrylamide. Haemoglobin adducts of acrylamide and its oxidative metabolite glycidamide are both markers of biochemical effect. However, because glycidamide has a higher carcinogenic potency than acrylamide itself, the glycidamide adduct might mirror the genotoxicity better than acrylamide adducts. In order to gain more information about the human metabolism of acrylamide, we investigated a small group of persons for the effective internal doses of acrylamide and glycidamide using haemoglobin adducts as parameters of biochemical effect.

The collective was subdivided into non-smokers (n=13) and smokers (n=16) by determining the smoking-specific acrylonitrile haemoglobin adduct (N-cyanoethylvaline, CEV). The mean values for the adducts of acrylamide (N-2-carbamoylethylvaline, AAVal) and glycidamide (N-(R,S)-2-hydroxy-2-carbamoylethylvaline, GAVal) in nonsmokers was 19 pmol/g globin AAVal (range 7 – 31 pmol/g globin) and 17 pmol/g globin GAVal (range 9 – 23 pmol/g globin). For smokers mean levels of AAVal were 80 pmol/g globin (range: 25 – 199 pmol/g globin) and those of GAVal were 53 pmol/g globin (range: 22 – 119 pmol/g globin). Metabolism to glycidamide turned out to be significantly more effective in non-smokers than in the higher exposed smokers. Compared with studies in rats, the metabolic conversion of acrylamide to glycidamide as measured by haemoglobin adducts seems to occur to a similar extent in humans as in rats. Risk estimations on acrylamide based on experimental data obtained in rats obviously did not overestimate the cancer risk for the general population. Furthermore, our results might indicate that the dose-response curve for acrylamide is not linear. This would be in line with the results of animal experiments on rodents.     

Excretion of PFOA and PFOS in Male Rats During a Subchronic Exposure

Perfluorinated compounds (PFCs), a class of synthetic surfactants that are widely used, have become global environmental contaminants because of their high persistence and bioaccumulation. An increasing number of studies have described the pharmacokinetics of PFCs following in vivo exposure, however, few papers have focused on the excretion of these compounds during a period of consecutive exposure. In this study, the excretions of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in male Sprague–Dawley rats gavaged consecutively for 28 days were investigated and compared. The faster elimination rate in urine compared to feces indicated that urinary excretion is the primary clearance route in rats for either PFOA or PFOS. During the first 24 h after administration of PFOA (5 and 20 mg/kg body weight/day), about 24.7–29.6% of the oral dose was excreted through urine and feces, while for PFOS, the excretion amounts were only 2.6–2.8% of the total gavaged doses (5 and 20 mg/kg body weight/day). The excretion rates of both PFCs increased with increasing exposure doses. The higher elimination rate of PFOA through excretion indicated its lower accumulation in rats, thus inducing possible lower toxicities compared to PFOS.     

The effect of a single oral dose of ethyl linoleate on urinary prostaglandin E2 excretion in essential fatty acid-deficient rats

The effects of a single oral dose of ethyl linoleate on urinary prostaglandin E2 (PGE2) excretion and urine output were investigated in essential fatty acid (EFA)-deficient rats. Weanling male rats were fed a fat-free diet. After 13 wk of feeding, eight rats received an oral dose of 400 mg of ethyl oleate. Seven days later the same eight rats received 400 mg of ethyl linoleate. The oleate dosage served as control. Another seven EFA-deficient rats received an oral dose of 100 mg of ethyl linoleate. The 24-h urine collections from each animal were analyzed for PGE2 by radioimmunoassay. Within 24 h the oleate dose resulted in a 1.3-fold increase in urinary PGE2 excretion. The 400-mg dose of ethyl linoleate induced a 2- to 3-fold increase in urinary PGE2 excretion during 7 d. The 100-mg dose of ethyl linoleate resulted in a 1.3- to 1.5-fold increase for 2 d. Neither the ethyl oleate dose nor the low dose of ethyl linoleate had any effect on urine output, whereas the high dose of ethyl linoleate induced a slow increase during the following 6 d. The present results show that a single dose of 400 mg of ethyl linoleate increased urinary PGE2 excretion and urine output in EFA-deficient rats. However, these two parameters do not seem to be correlated. The amount of urinary PGE2 excreted in excess of baseline urinary PGE2 excretion accounted on a molar basis for less than 1 ppm of the administered dose of ethyl linoleate.     

Biomarkers of individual susceptibility to carcinogens: Application for biological monitoring

In order to develop new markers of individual susceptibility to various human carcinogens, we studied some parameters of formation and metabolism of carcinogens, as well as DNA adducts formation and DNA repair in animals and humans. Following an i.p. administration of benzo(a)pyrene (BP) to the rats, levels of urinary excretion of BP-7,8-diol correlated with tumour latency. A high correlation was found between excretion of this metabolite and BP-DNA adducts level in the liver. Healthy smokers excreted higher quantities of BP-7,8-diol, than smoking lung cancer patients, thus confirming the suggestion on existence of cancer-prone phenotype. N-nitroso compounds formed most efficiently in stomach juice of children with superficial gastritis who therefore could be at high risk of stomach cancer. N-ethyl-N-nitro-N-nitrosoguanidine induced stomach cancer earlier in monkeys with a low level of DNA repair enzyme, O⁶-alkylguanine-DNA alkyltransferase (AGT) in gastric mucosa. Overall, these markers can be helpful in predicting individual susceptibility to carcinogens.     

GC/MS determination of N-phenylvaline,a possible biomarker for benzene exposure in human hemoglobin by the “N-alkyl Edman method”

Summary We report the application of a modified Edman degradation procedure to the analysis of benzene oxide adducts at the N-terminal valine of human hemoglobin (Hb). Benzene oxide is thought to be formed in the liver from benzene and adduct formation with macromolecules is therefore likely to occur. We assumed that benzene oxide could covalently bind to hemoglobin after leaving the hepatic tissue. The N-alkyl Edman method was adapted for the approach to investigate this hypothesis. Using capillary gas chromatography/mass spectrometry (GC/MS) with negative chemical ionization, we could not detect N-phenylvaline in blood samples from persons occupationally exposed to benzene. We conclude that adducts of benzene oxide to the N-terminal valine of Hb are not formed in detectable amounts in vivo and consequently are not suitable for biomonitoring purposes. This result clearly indicates that other reactive benzene metabolites have to be taken into account not only in the search for a biomarker but also as the ultimate carcinogenic species.     

Effect of dietary fiber on the disposition and excretion of a food carcinogen (2‐14c‐labeled MeIQx) in rats

We studied to what extent dietary fiber may affect uptake, retention, and excretion of a food carcinogen (2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline, MeIQx) occurring in fried meat. Four diets—one fiber‐free control and three containing either insoluble dietary fiber isolated from sorghum (100 g/kg) and wheat bran (100 g/kg) or the highly soluble pectin (50 g/kg) — were investigated. The fiber diets were given in amounts of 10 g/day to rats. Thus, each rat received 1 or 0.5 g fiber and 100 μg 2‐¹⁴C‐labeled MeIQx uniformly mixed in its daily diet. A 4‐day adaptation period with unlabeled MeIQx was followed by a 5‐day experimental period with ¹⁴C‐labeled MeIQx, during which urine and feces were collected separately for analysis of radioactivity and mutagenicity. Furthermore the composition and the ferment‐ability of the dietary fiber were determined. The present study shows that a diet containing fiber, especially fiber isolated from sorghum and wheat bran, affects the excretion pattern of the food carcinogen MeIQx in a manner suggesting a lower uptake and a decreased transit time through the gastrointestinal tract in a more diluted form than a nonflber diet. Furthermore, less radioactivity was retained in the kidneys with sorghum and wheat bran than with the other two diets. On the other hand, none of these types of dietary fiber affected the retention of the hepatocarcinogen MeIQx in the liver 24 hours after the last oral intake. DNA adducts were formed to a higher extent in the kidney than in the liver. The highest levels were found in animals given the wheat bran diet.     

Fate of the mushroom hydrazine agaritine in the rat and mouse

The fate of the mushroom hydrazine [14C]agaritine was investigated in the mouse and rat strains previously employed in carcinogenicity studies with the edible mushroom Agaricus bisporus. Agaritine was rapidly absorbed in both species, achieving higher blood levels in the mouse, but with similar area under the curve. Covalent binding of agaritine material to proteins was detected only in the liver and kidney, but the extent of binding was the same in the rat and mouse. Most of the radioactivity was excreted during the first 24 hours in both animal species: in the rat it was distributed equally between urine and feces, whereas in the mouse more of the radioactivity was excreted in the urine. No qualitative differences in the metabolic profile were evident, but quantitative differences were observed. Treatment of the urine with deconjugating enzymes did not reveal the presence of any conjugates. Agaritine, N'-acetyl-4-(hydroxymethyl)phenylhydrazine, and 4-(hydroxymethyl)benzene diazonium ion were not detected in the urine or in the plasma of either species. No mutagens or promutagens were detected by the Ames mutagenicity assay in the urine of either species after exposure to agaritine. Repeated administration of agaritine to rats and mice did not alter the urinary metabolic profile and excretion of radioactivity. Similarly, feeding mice a raw mushroom diet, according to the protocol employed in the carcinogenicity studies, did not modulate the excretion of radioactivity or the urinary metabolic pattern. No major species differences in the fate of agaritine in rat and mouse were noted that could provide a rationale for the carcinogenicity of A. bisporus in the mouse, but not in the rat.     

Urinary excretion of n-hexane metabolites in rats and humans

Summary The urinary excretion of n-hexane metaboites was studied in rats which were either treated or not with phenobarbital before n-hexane treatment and in workers occupationally exposed to n-hexane.A new hexane metabolite, 3-hexanol, and 2-hexanol were found in rat urine, but not in workers' urine. The amount of 2-hexanol excreted during 24 h after n-hexane administration, was equal to 1.2 – l.7 % of the dose. The ratio between 3-hexanol excreted and n-hexane injected was much less than 1 %. Phenobarbital affected 3-hexanol excretion but not 2-hexanol excretion.The lack of n-hexane metabolites in workers' urine, which can be explained by the low ratio of metabolite excretion to the n-hexane absorbed, suggests that urine analysis is unsuitable for monitoring hexane exposure during work.