Inhalation exposure to 1,3-dichloropropene in the Dutch flower-bulb culture. Part II. Biological monitoring by measurement of urinary excretion of two mercapturic acid metabolites

Abstract

A biological monitoring study was carried out in the Dutch flower-bulb culture to determine the relationship between respiratory occupational exposure to Z- and E-1,3-dichloropropene (Z- and E-DCP) and urinary excretion of two mercapturic acid metabolites, N-acetyl-S-(Z- and E-3-chloropropenyl-2)-L- cysteine (Z- and E-DCP-MA). Urinary excretion of Z- and E-DCP-MA, either based on excretion rates or on creatinine excretion, followed first order elimination kinetics after exposure. Urinary half-lives of elimination were 5.0 +/- 1.2 hr for Z-DCP-MA and 4.7 +/- 1.3 hr for E-DCP-MA and were not statistically significantly different. Calculated coefficients of variation indicated that the half-lives of elimination of Z- and E-DCP-MA were quite consistent inter- and intra-individually. Strong correlations (r greater than or equal to 0.93) were observed between respiratory 8-hr time weighted average (TWA) exposure to Z- and E-DCP and complete cumulative urinary excretion of Z- and E-DCP-MA. Z-DCP yielded three times more mercapturic acid than E-DCP, probably due to differences in metabolism. Z- and E-DCP were excreted 45 and 14% as their respective mercapturic acid metabolites. A respiratory 8-hr TWA exposure to the Dutch occupational exposure limit of 5 mg.m-3 DCP would result in a complete cumulative excretion of 14.4 mg (95% confidence interval: 11.7-17.0 mg) Z-DCP-MA and 3.2 mg (95% confidence interval: 2.3-4.1 mg) E-DCP-MA.

Personal air sampling and biological monitoring of occupational exposure to the soil fumigantcis-1,3-dichloropropene

“…These data are in good agreement with the results of Van Welie et al 2. The correlation between the 8 hour TWA air concentration of cis -DCP and the concentration of cis -DCP-MA in urine, found by these investigators were r =0.71 in end of shift urine samples and r =0.94 in 24 hour urine samples.…”

“…2 Brouwer et al 3 reported that 8 hour time weighted average (TWA) exposures to cis/trans -DCP ranged from 1.9 to 18.9 mg/m 3 . The Dutch OEL of 5 mg/m 3 (1 ppm) was exceeded during 30% of the observed working days.…”

Analyses of representative biomarkers of exposure and effect by chromatographic, mass spectrometric, and nuclear magnetic resonance techniques: Method development and application in life sciences

“…Therefore, though urinary MAs are frequently used as biomarkers of internal dose, they are sometimes also classified as biomarker of effect [22]. Several recent and older examples of MAs used in the BM of human exposure or in biotransformation studies are: N-acetyl-S-(9,10-dihydro-9-hydroxy-10-phenanthryl)-L-cysteine, which originates from a polycyclic aromatic hydrocarbon, phenanthrene, present in cigarette smoke [23], four structurally different mercapturates derived from the herbicides atrazine, acetochlor, metolachlor, and alachlor [24], S-acetamidomethylmercapturic acid, in response to exposure to the industrial solvent N,N-dimethylacetamide [25], N-acetyl-S-(p-chloro- phenylcarbamoyl)cysteine, derives from the anticancer agent sulofenur [26], phenyl mercapturic acid, in response to benzene exposure in industry [27], 3,4-dihydroxybutylmercapturic acid as an environmental and biological monitoring indicator of non-occupational exposure to 1,3-dichloropropene [28], 3-chloro-2-hydroxypropylmercapturic acid and allylmercapturic acid as urinary biomarkers of human exposure to allyl chloride [29], and N-acetyl-S-(Z-and E-3-chloropropenyl-2)-L-cysteine as a biomarker for agricultural soil fumigant 1,3-dichloropropene [30]. In the first part of the studies summarized in this Review, attention is paid to MA derivatives of volatile anesthetics in humans, and whether they are applicable as biomarkers of effect.…”

1,3-Dichloropropene

“…The mercapturic acid conjugate of 1,3-D has also been identified in the urine of human subjects exposed to mixed isomer vapors of 1,3-D under field application or laboratory conditions and has been utilized as a biomonitor of 1,3-D exposure (Kezic et al, 1996;Osterloh and Feldman, 1993;Osterloh et al, 1984;van Welie et al, 1991;Waechter et al, 1992). Consistent with the earlier rat data, Waechter et al (1992) found that humans excrete approximately 45% and 14% of absorbed cis-and trans-isomers of 1,3-dichloropropene, respectively, as the cis-and transmercapturates, a 3.2:1 ratio.…”

“…Based upon these data, it has been proposed that 1,3dichloropropene is primarily metabolized in rats and mice, and humans, by conjugation with glutathione and by hydrolysis of the 3-position chlorine (Bartels et al, 2004;Dietz et al, 1984;Fisher and Kilgore, 1988a;Hutson et al, 1971;IPCS, 1993;Onkenhout et al, 1986;Osterloh et al, 1984;van Welie et al, 1991;Waechter et al, 1992). The end-product of the latter pathway is CO 2 .…”