Chlorophenols in urine

R. Galve, M. Nichkova, F. Camps, F. Sanchez-Baeza, and M.P. Marco, Development and evaluation of an immunoassay for biological monitoring chlorophenols in urine as potential indicators of occupational exposure. Anal. Chem. 74, 468-478 (2002). 

Table VII. Levels of Chlorophenols in Urine of Exposed Workers.

Among the most frequently used organic solvents is chloroform, used for the determination of many analytes in various samples free cyanide and thiocyanate ions in human saliva chlorophenols in urine and Bi(III), ethambutol hydrochloride, diclofenac, phenothiazine derivatives, imipramine, warfarin, flufenamic acid, and ethylmorphine in pharmaceutical preparations. Another proposed solvent is dichloro-ethane, used for the determination of bromhexine in serum and imipramine, ambroxol, berberine, bromhexine, neostigmine, 8-chlorotheophylline, and diphenhydramine in pharmaceutical samples. 

PCDDs and PCDFs were also found at similar levels in-blood following a 6-8 months1 long period of non-exposure as compared to samples taken after one month of exposure, although the level of chlorophenols in the urine increased up to 100 times after the period of exposure. Consequently no good correlation was found between the blood and urine analyses. 

Studying occupational exposure to highly contaminated chlorophenols, the analysis of PCDDs and PCDFs in blood samples seems to be a better parameter to follow than the level of chlorophenol in the urine. 

The highest concentrations of studied chlorophenols (2,4-, 2,4,6- and 2,3,4,6-) have been found in kidney, liver and spleen and the lowest concentrations in muscle and brain, either after parenteral administration of these chlorophenols themselves or as metabolites of other organochlorine compounds. Over 80% of the dose is excreted in urine and 5-20% in faeces. Metabolism varies somewhat depending on chlorine content the low-chlorine substances tend to be excreted as glucuronide and sulfate conjugates with higher chlorine substitution, excretion of the unchanged substance tends to increase. Formation of chlorinated 1,4-quinones is a minor pathway except for 2,3,5,6-tetrachlorophenol (WHO, 1989). 

Nichkova, M. and M.R Marco. 2005. Development and evaluation of C18 and immunosorbent solid-phase extraction methods prior to immunochemical analysis of chlorophenols in human urine. Anal. Chim. Acta 533 67-82. 

Acetates of fatty [1] and polyhydric [2] alcohols, phenols [3] and chlorophenols [4] have been studied. Fell and Lee [3] described a GC method for the determination of polyhydric phenols in urine, which, having been extracted, were acetylated with acetic anhydride in the presence of 4-dimethylaminopyridine. According to these authors this substance shows much stronger catalytic effects than does the usually used pyridine. The derivatives are formed rapidly and quantitatively even in very dilute solutions. In the absence of the catalyst, bifunctional phenols provide more than one GC peak. Slightly polar OV-210 is recommended for the separation of phenol acetates, but analysis on nonpolar OV-101 leads to tailing, probably as a consequence of insufficient deactivation of the column. 

OSHA PEL TWA 0.5 mg(As)/m3 ACGIH TLV BEL 35 n (As)/L inorganic arsenic and methylated metabolites in urine SAFETY PROFILE Poison by intravenous, intraperitoneal, and possibly other routes. Moderately toxic by ingestion. Human systemic effects by parenteral route hypermotility, diarrhea, nausea, vomiting. See also ARSENIC COMPOUNDS and CHLOROPHENOLS. When heated to decomposition it emits ver toxic fumes of As, NOx, and Cl". 

Methods such as standard addition only provide good results with a relatively simple matrices. One of the main problems when a first-order multivariate model is used is the presence of unknown interferences. Mathematical models have become very important for solving this problem an example is the determination of five pollutants of the chlorophenol family in urine. The effect of the matrix is minimized by including, in the calibration step, standard samples containing the analytes in the presence of the interfering matrix. The calibration set includes 60 standard samples 50 samples of chlorophenols in water and 10 of lyophilized urine. 

Gas Chromatographic Analysis of Penta-chlorophenol in Human Urine by Formation of Alkyl Ethers Life Sci. 9(3) 121-128 (1970) CA 72 131288J... 

Most studies in TLC have been qualitative, and considerable experimentation may be necessary to obtain quantitative results, although excellent commercial layers and new equipment have aided the problem. Phenolic compounds have been analyzed by spectrophotometry off the plate at 725 nm (133) by means of Folin-Ciocalteu reagent, essentially sodium tungstate and molybdate with lithium sulfate (134). Chlorophenols have been quantified after reaction with dansyl chloride and separation (135). Channel TLC (linear relationships between spot lengths and concentration between 1 and 8 pg/spot) has been used (136). The phenols in cashew nut shell liquid have been quantified by off and on the plate methods with a flying-spot scanning procedure and densitometry (137) and the distribution of unsaturateds by TLC/MS (138). Catecholamines and their metabolites in urine have been quantified (12) and determined by on the plate fluorimetry (139). Hindered phenols have been analyzed by densitometry (140). Semiquantitative determinations of the coupling products of 4,4 -... 

Lindane metabolism in urine Chlorophenols Silufol /I-C6H 4-CtH6- EtOAc (6 4 1) AgN03/Mc2CO UV Adsorption l-D 57 Sensitivity 1 ppm (combined GC/TLC)... 

Renal Effects. Although not adverse, dark urine (as a result of oxidation products of phenol or a result of hemoglobin or its breakdown products in the urine) is a common symptom observed in humans exposed to phenol. In persons exposed to about 0.14-3.4 mg/kg/day phenol in drinking water for several weeks after an accidental spill, dark urine was reported by 17.9% of the most highly-exposed individuals, while only 3.4% of the controls reported the effect (Baker et al. 1978). This difference was not statistically significant. A 3.3-fold increase in the prevalence of dark urine was reported by persons exposed to unspecified doses of phenol after an accidental spill in Korea (Kim et al. 1994). It is not known if the chlorination process, which may have converted a majority of the phenol to chlorophenol, contributed to this effect. 

In Table VII the levels of chlorophenols found in the urine from a variety of occupationally exposed groups have been collected. 

One of the branches under study is the saw-mill industry. In Finland 2,3,, 6-tetrachlorophenol is used for bluestain control of the timber during the summer season (May - OctoberI. It is known that PCDFs are the major contaminants in this particular formulation, see Table III. The sampling was performed twice, the first set of samples was taken after 6 months of non-exposure. The other sampling was performed after one month of chlorophenol exposure. In Table VIII we have collected the levels of chlorophenols found in the urine samples as well as the levels of PCDDs and PCDFs found in the blood samples. 

The absorption of 2,4-dichloro-, 2,4,5-trichloro-, 2,4,6-trichloro-, 2,3,4,5- and 2,3,4,6-tetrachlorophenol is relatively rapid when they are given orally, dermally or by inhalation. Chlorophenols are almost exclusively metabolized to conjugates which are mainly excreted in the urine. Half-lives are from hours to days, the compounds with higher chlorine content having longer half-lives (lARC, 1986). 

Lindsay-Smith et al. (1972) reported that the major metabolites of chlorobenzene in the rabbit are p-chlorophenylmercapturic acid and conjugates of 4-chlorocatechol. Other urinary metabolites included quinol, 3- chlorocatechol, and o-and m-chlorophenylmercapturic acids. Oesch et al. (1973) studied the metabolism of chlorobenzene in rats administered chlorobenzene by intraperitoneal injection. Thirty-three percent of the administered dose was excreted in the urine, with p-chlorophenol as the major metabolite. Other metabolites included 4-chlorocatechol, o-chlorophenol, and m- chlorophenol. 

Disposition in the Body. Readily absorbed after oral administration. About 85% of a dose is excreted in the urine as a glucuronide conjugate in 24 hours together with small amounts of unchanged drug, and the oxidised metabolites, 4-chlorophenoxylactic acid, 4-chlorophenoxyacetic acid and 4-chlorophenol. 

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