Evidence that a beta-N-glucuronide of 4,4'-methylenebis (2-chloroaniline) (MbOCA) is a major urinary metabolite in man: implications for biological monitoring.

Cocker, John; Boobis, Alan R.; Wilson, H K; Gompertz, D.

doi:10.1136/oem.47.3.154

Cited by 11 publications

(18 citation statements)

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“…In this way, free MOCA, acid-labile MOCA and total MOCA determinations were performed in each urine sample; the heat-labile MOCA was determined according to the procedure described by Cocker et al (1990) in 17 urine samples of workers from the four factories.…”

Section: Urine Storage and Analysismentioning

confidence: 99%

“…On 17 of the urine samples of workers (potentially exposed to MOCA) collected without acid protection, kept frozen at A20°C until analysis, and thawed just before treatment, we also measured the MOCA released in each specimen after heat hydrolysis (``heat-labile'' MOCA) under the conditions described by Cocker et al (1990) (80°C for 45 min).…”

Section: Eciency Of Heating the Urine Samplesmentioning

confidence: 99%

“…However, Cocker et al (1990) showed that the measurement of free MOCA in worker's urine samples is greatly in¯uenced by the preanalytical treatment of the sample, leading to erroneous estimates of relative exposure; they suggested that MOCA released after heat hydrolysis of urine samples (80°C for 45 min) could be a better marker for MOCA exposure. The hydrolysis step would take account of the heat-labile N-glucuronide metabolites of MOCA, and the measurement of MOCA on heated urine samples would overcome changes in the free MOCA concentration caused by¯uctuations of urinary concentrations at ambient temperature, also due to the time between voiding and analysis of urine samples.…”

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confidence: 99%

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Biological monitoring of workers exposed to 4,4′-methylene-bis-(2-orthochloroaniline) (MOCA)

Robert¹,

Ducos²,

Francin³

1999

International Archives of Occupational and Environmental Health

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Section: Urine Storage and Analysismentioning

confidence: 99%

Section: Eciency Of Heating the Urine Samplesmentioning

confidence: 99%

mentioning

confidence: 99%

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Biological monitoring of workers exposed to 4,4′-methylene-bis-(2-orthochloroaniline) (MOCA)

Robert¹,

Ducos²,

Francin³

1999

International Archives of Occupational and Environmental Health

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“…He did not wear any personal protective equipment during work. Workers may inhale small particles of MBOCA in the air or absorb the agent through the skin if they come into contact with MBOCA dust or vapor (Chin et al 1983; Cocker et al 1988, 1990; Ichikawa et al 1990; NIOSH 1986). According to the environmental monitoring data for the patient’s factory, he may have been exposed to high concentrations of MBOCA through inhalation or dermal absorption.…”

Section: Discussionmentioning

confidence: 99%

Occupational Bladder Cancer in a 4,4′-Methylenebis(2-chloroaniline) (MBOCA)-Exposed Worker

Liu

Liou

Loh

et al. 2005

Environ Health Perspect

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A 52-year-old male chemical worker was admitted to the hospital with a history of paroxysmal microscopic hematuria for about 2 years and nocturia with gross hematuria about five times per night for 2 months. He was a nonsmoker and denied a history of any other bladder carcinogen exposure except for occasional pesticide application during agricultural work. Intravenous urogram imaging showed a mass occupying half of the bladder capacity. Cystoscopy revealed a mass over the left dome of the bladder. Cystoscopic biopsy revealed a grade 3 invasive transitional cell carcinoma with marked necrosis. From 1987 until hospital admission in 2001, the patient had worked in a company that produced the 4,4′-methylenebis(2-chloroaniline) (MBOCA) curing agent. He did not wear any personal protective equipment during work. Ambient air MBOCA levels in the purification process area (0.23–0.41 mg/m3) exceeded the U.S. Occupational Safety and Health Administration’s permissible exposure level. Urinary MBOCA levels (267.9–15701.1 μg/g creatinine) far exceeded the California Occupational Safety and Health Administration’s reference value of 100 μg/L. This patient worked in the purification process with occupational exposure to MBOCA for 14 years. According to the environmental and biologic monitoring data and latency period, and excluding other potential bladder carcinogen exposure, this worker was diagnosed as having occupational bladder cancer due to high exposure to MBOCA through inhalation or dermal absorption in the purification area. This case finding supports that MBOCA is a potential human carcinogen. Safe use of skin-protective equipment and respirators is required to prevent workers from MBOCA exposure.

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“…MOCA is an aromatic amine and a suspected human carcinogen (IARC 1993). It is excreted mainly as N-glucuronide in urine of exposed workers (Cocker et al 1990). Creosote oil is also suspected for human carcinogenicity (IARC 1987) and it is a likely inducer of pyrene metabolism as it contains a number of PAH compounds, including pyrene itself.…”

Section: Discussionmentioning

confidence: 99%

Characterization of 1‐Hydroxypyrene as a Novel Marker Substrate of 3‐Methylcholanthrene‐Inducible Phenol UDP‐Glucuronosyltransferase(s)

Luukkanen

Elovaara

Lautala

et al. 1997

Pharmacology & Toxicology

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Rats were treated with acetone, pyrazole, phenobarbital, 4,4'-methylenebis-(2-chloroaniline) (MOCA), 3-methylcholanthrene, creosote oil, or a mixture of polychlorinated biphenyls (Aroclor 1254) to study the inducibility and enzyme kinetics of UDP-glucuronosyltransferases towards 1 -hydroxypyrene, which is a human metabolite and a urinary biomarker of exposure to pyrene. The rate of I-hydroxypyrene glucuronidation was analysed in rat liver microsomes by a fluorometric HPLC assay of the formed glucuronide. The apparent K, and V, , , values in untreated controls (K,= 0.27 mM; Vm,,=31 nmol/min./mg protein) did not differ markedly from those in rats treated with acetone, pyrazole or phenobarbital, whereas the significantly decreased K, and increased V, , , values of the rats treated with the carcinogenic chemicals, MOCA (0.11; 51), creosote (0.06; 137), 3-methylcholanthrene (0.07; 141) or the Aroclor-1254 polychlorinated biphenyl (PCB) mixture (0.08; 226), implicated major changes in the hepatic expression of UDP-glucuronosyltransferases. I-Hydroxypyrene proved to be a high affinity substrate and a sensitive marker of the polycyclic aromatic hydrocarbon (PAH) metabolizing UDP-glucuronosyltransferase(s). Catalytically, the most efficient isoforms were induced in creosote, 3-methylcholanthrene and PCB-treated rats showing V,,,/K,,, ratios which were 22-27 times greater than in untreated controls. Our findings suggest the existence of a 3-methylcholanthrene type inducible and a functionally efficient low-K,/ high-V,,, form(s) of UDP-glucuronosyltransferase(s) that detoxify 1-hydroxypyrene and probably other polycyclic aromatic hydrocarbons as well.

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Evidence that a beta-N-glucuronide of 4,4'-methylenebis (2-chloroaniline) (MbOCA) is a major urinary metabolite in man: implications for biological monitoring.

Abstract: Urine samples from workers exposed to 4,4'-methylenebis (2-chloroaniline) (MbOCA) contain a labile metabolite(s) that, on hydrolysis, yields the parent compound at concentrations two to three times those of free MbOCA. Evidence has now been obtained that the

Cited by 11 publications

References 11 publications

Biological monitoring of workers exposed to 4,4′-methylene-bis-(2-orthochloroaniline) (MOCA)

Biological monitoring of workers exposed to 4,4′-methylene-bis-(2-orthochloroaniline) (MOCA)

Occupational Bladder Cancer in a 4,4′-Methylenebis(2-chloroaniline) (MBOCA)-Exposed Worker

Characterization of 1‐Hydroxypyrene as a Novel Marker Substrate of 3‐Methylcholanthrene‐Inducible Phenol UDP‐Glucuronosyltransferase(s)

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