Development of a Biomarker for Penconazole: A Human Oral Dosing Study and a Survey of UK Residents’ Exposure

Abstract

Penconazole is a widely used fungicide in the UK; however, to date, there have been no peer-reviewed publications reporting human metabolism, excretion or biological monitoring data. The objectives of this study were to i) develop a robust analytical method, ii) determine biomarker levels in volunteers exposed to penconazole, and, finally, to iii) measure the metabolites in samples collected as part of a large investigation of rural residents' exposure. An LC-MS/MS method was developed for penconazole and two oxidative metabolites. Three volunteers received a single oral dose of 0.03 mg/kg body weight and timed urine samples were collected and analysed. The volunteer study demonstrated that both penconazole-OH and penconazole-COOH are excreted in humans following an oral dose and are viable biomarkers. Excretion is rapid with a half-life of less than four hours. Mean recovery of the administered dose was 47% (range 33%-54%) in urine treated with glucuronidase to hydrolyse any conjugates. The results from the residents' study showed that levels of penconazole-COOH in this population were low with >80% below the limit of detection. Future sampling strategies that include both end of exposure and next day urine samples, as well as contextual data about the route and time of exposure, are recommended.

Assessment of penconazole exposure in winegrowers using urinary biomarkers

“…As for urinary metabolites, PEN-OH and PEN-COOH, concentrations in the range 1.2 to 237 μg/L for PEN-OH and <1 to 54 μg/L for PEN-COOH, were found. These results confirm the previous findings on PEN-OH being much higher than PEN-COOH in human urine, even if the ratio between the two is about 5, lower than 20, the ratio previously reported , and similar to that found after oral administration of PEN to three human volunteers (Sams et al, 2016).…”

“…In study subjects, absorption of skin deposed pesticide is the major exposure route, and continues over the working time. Considering this scenario, our result is consistent with that of a study in which PEN was orally administered to three human volunteers, and a half time of few hours (3-5 h) was observed for PEN-OH in urine (Sams et al, 2016). Moreover, the kinetics study suggests that the best time for sample collection is the 24 h-interval following exposure, or in case of multiple consecutive exposures, the 24 h-interval following the last exposure.…”

“…In this study, 89 urine samples from 48 resident adults and six children were collected after the spray event; in these samples the percentage of detectable PEN-COOH was 19% (limit of detection 0.25 µg/L) and the 95th and maximum levels were 0.9 and 5.1 µg/g creatinine. These levels were slightly higher, but comparable to those obtained in background urine samples of the general population, both within and outwith the spray season (95th percentile 0.8 and 0.6 µg/g creatinine, respectively, maximum 3.3 and 4.8 µg/g creatinine, respectively) (Sams et al, 2016). As expected, these levels, were much lower than those found in the present study for agricultural workers.…”

“…Median ratio between , highlighting that in humans PEN is mostly metabolized and excreted as PEN-OH, both as glucuronide conjugated and in the free form (see Figure 1) Sams et al, 2016).…”

“…Recently, the metabolism of PEN in humans was investigated Sams et al, 2016), showing that the major urinary metabolites are the monohydroxyl-derivative PEN-OH, mostly excreted as glucuronide conjugated, and the carboxyl-derivative PEN-COOH, although with a minor contribution (see Figure 1). Based on this result, we suggested the measurement of PEN-OH concentration in urine, after the hydrolysis of the glucuronide conjugate, for the biological monitoring of PEN exposure .…”