Urinary levels

Neurological effects related to cholinesterase depression occurred in seven children acutely exposed to methyl parathion by inhalation as well as orally and dermally (Dean et al. 1984). The children were admitted to a local hospital with signs and symptoms of lethargy, increased salivation, increased respiratory secretions, and miosis. Two of the children were in respiratory arrest. Two children died within several days of each other. All of the children had depressed plasma and erythrocyte cholinesterase levels (Table 3-2). These effects are similar to those occurring in methyl parathion intoxication by other routes (see Sections 3.2.2.4 and 3.2.3.4). Three adults exposed in the same incident had normal plasma (apart from one female) and red blood cell cholinesterase, and urinary levels of 4-nitrophenol (0.46-12.7 ppm) as high as some of the ill children. 

Hauser, R., Meeker, J.D., and Singh, N.R et al. (2007). DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Human Reproduction 22, 688-695. 

As the name implies, the odor of urine in maple syrup urine disease (brancbed-chain ketonuria) suggests maple symp or burnt sugar. The biochemical defect involves the a-keto acid decarboxylase complex (reaction 2, Figure 30-19). Plasma and urinary levels of leucine, isoleucine, valine, a-keto acids, and a-hydroxy acids (reduced a-keto acids) are elevated. The mechanism of toxicity is unknown. Early diagnosis, especially prior to 1 week of age, employs enzymatic analysis. Prompt replacement of dietary protein by an amino acid mixture that lacks leucine, isoleucine, and valine averts brain damage and early mortality. 

Decarboxylation of histidine to histamine is catalyzed by a broad-specificity aromatic L-amino acid decarboxylase that also catalyzes the decarboxylation of dopa, 5-hy-droxytryptophan, phenylalanine, tyrosine, and tryptophan. a-Methyl amino acids, which inhibit decarboxylase activity, find appfication as antihypertensive agents. Histidine compounds present in the human body include ergothioneine, carnosine, and dietary anserine (Figure 31-2). Urinary levels of 3-methylhistidine are unusually low in patients with Wilson s disease. 

An update of a previous study (Axelson et al. 1978), Axelson (1986) evaluated an expanded cohort of 1,424 men (levels of trichloroethylene exposure inferred from measured urinary metabolite concentrations) and found a significant increase in incidences of bladder cancer and lymphomas, and a lower than expected incidence of total cancer mortality. A further update of this work (Axelson et al. 1994) expanded the cohort to include 249 women, tracking cancer morbidity over 30 years, and found no correlation between exposure concentration or exposure time and cancer incidence at any site. The highest standardized incidence ratio noted in this study was 1.56 (95% Cl of 0.51-3.64) for 5 cases of non-Hodgkin s lymphoma observed in men. Although four of these cases occurred in persons exposed for at least 2 years, and 3 cases had a latency of 10 years or more, urinary levels of TCA showed that 4 of the 5 cases were exposed to the lowest levels of trichloroethylene (urinary levels of TCA 0-49 mg/L). The study authors mentioned that a urinary TCA level below 50 mg/L corresponds to a trichloroethylene exposure concentration of about 20 ppm. The study authors concluded that "this study provides no evidence that trichloroethylene is a human carcinogen, i.e., when the exposure is as low as for this study population."... 

Sex differences in the urinary excretion of metabolites of trichloroethylene have been reported (Inoue et al. 1989 Nomiyama and Nomiyama 1971). In trichloroethylene-exposed workers, urinary levels of trichloro compounds and trichloroethanol were significantly higher in men than in women, while urinary levels of TCA did not differ between the two sexes (Inoue et al. 1989). However, it was reported that excretion of TCA in urine was greater in women than in men within 24 hours of exposure (Nomiyama and Nomiyama 1971). 

In a clinical trial performed in China, the administration of 300 mg/day of copper chlorophyllin to humans who had detectable levels of serum aflatoxin due to unavoidable food contamination resnlted in a 50% reduction of median urinary levels of aflatoxin-DNA adducts. If health benefits from consuming natural chlorophylls were confirmed, it wonld be easy to add green leafy vegetables to a daily diet to obtain the benefit. Since leafy vegetables contain usually up to 200 mg chloro-phylls/100 g fresh weight, the intake of approximately 1 to 2 cups of raw spinach/day... 

During a 16-day vacation and plant shutdown, urinary excretion accounted for 90% elimination in those with high initial PCP levels (i.e., >0.1 mg/L) to 67% elimination in those with initial urinary levels of 0.02-0.1 mg PCP/L, and to 34% reduction in workers with <0.02 mg/L Tb 1/2 was estimated at 33 h in urine and 30 h in plasma (Kalman and Horstman 1983)... 

Hsueh, Y.M., Y.L. Huang, C.C. Huang, W.L. Wu, H.M. Chen, M.H. Yang, L.C. Lue, and C.J. Chen. 1998. Urinary levels of inorganic and organic arsenic metabolites among residents in an arseniasis-hyperendemic area in Taiwan. Jour. Toxicol. Environ. Health 54A 431-444. 

A decrease in the amplitude of the sensory nerve action potential has also been observed in a group of 20 asymptomatic workers exposed to -hexanc (Pastore et al. 1994). The subjects of this study were selected on the basis of urinary levels of the n-hexane metabolite 2,5-hexanedione (See Sections 2.3 and 2.7) exceeding 5 mg/L and compared to a group of unexposed laboratory workers. Mean years worked was 8.13 (range, 1.5—23 years). Sensory and motor nerve conduction velocities and distal latencies were normal in all nerves tested. However, significant decreases were found in sensory nerve action potential amplitude in the median, sural, and ulnar nerves. Neither the level of 2,5-hexanedione in urine nor age correlated with the changes in amplitude however, there was a significant correlation between years worked and amplitude. 

Following chronic occupational exposure to 0.19-0.75 ppm hydrogen cyanide, 24-hour urinary levels of thiocyanate were 6.23 (smokers) and 5.4 pg/mL (nonsmokers) in exposed workers as compared with 3.2 (smokers) and 2.15 pg/mL (nonsmokers) in the controls (Chandra et al. 1980). This study demonstrates that tobacco smoking contributes to higher thiocyanate levels excreted in the urine. No studies were located regarding excretion of cyanide in animals after inhalation exposure to cyanide. 

A study of workers from phenol production facilities did not find an association between phenol and mortality from various causes, including cancer (Dosemeci et al. 1991). Urinary levels of total phenol have been shown to correlate with atmospheric phenol concentration when there is limited dermal exposure, and no exposure to benzene (ACGIH 1991 Ohtsuji and Ikeda 1972). 

---