Stephan Koslitz

The contribution of diet to total bisphenol A body burden in humans: results of a 48 hour fasting study.

Human biomonitoring studies measuring bisphenol A (BPA) in urine have shown widespread exposure in the general population. Diet is thought to be a major route of exposure. We studied urinary BPA patterns in five individuals over a 48-h period of fasting (bottled water only). Personal activity patterns were recorded with a diary to investigate non-dietary routes of exposure. All urine void events during the fast were collected, as well as events before and after the fast. The pattern of BPA concentrations was similar for all participants: they rose near the beginning of the fast (after the pre-fast meal), declined over the next 24h, fluctuated at lower levels during the second day, and then rose after the post-fast meal. Concentrations (~2 μg/g creatine) and calculated BPA intakes (~0.03 μg/kg-day) in these individuals during the first 24h were consistent with general population exposures. For the second 24h, concentrations and intakes declined by about two-thirds. One of the individuals had an extraordinary pre-fast exposure event with concentrations rising as high as 98 μg/g creatine but declining to <5 μg/g creatine by day 2. Given patterns found in day 1 and the subsequent decline to lower levels in day 2, we hypothesize that BPA exposures in these individuals were diet-driven. No events in the diary (use of personal care products, e.g.) appear associated with exposures. On day 2, non-dietary sources may still be present, such as from dust. Another hypothesis is that small reservoirs of BPA from past exposures are released from storage (lipid reservoirs, e.g.) and excreted.

Quantification of four major metabolites of embryotoxic N-methyl- and N-ethyl-2-pyrrolidone in human urine by cooled-injection gas chromatography and isotope dilution mass spectrometry.

N-Methyl- and N-ethyl-2-pyrollidone (NMP and NEP) are frequently used industrial solvents and were shown to be embryotoxic in animal experiments. We developed a sensitive, specific, and robust analytical method based on cooled-injection (CIS) gas chromatography and isotope dilution mass spectrometry to analyze 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI), two newly identified presumed metabolites of NEP, and their corresponding methyl counterparts (5-HNMP, 2-HMSI) in human urine. The urine was spiked with deuterium-labeled analogues of these metabolites. The analytes were separated from urinary matrix by solid-phase extraction and silylated prior to quantification. Validation of this method was carried out by using both, spiked pooled urine samples and urine samples from 56 individuals of the general population with no known occupational exposure to NMP and NEP. Interday and intraday imprecision was better than 8% for all metabolites, while the limits of detection were between 5 and 20 μg/L depending on the analyte. The high sensitivity of the method enables us to quantify NMP and NEP metabolites at current environmental exposures by human biomonitoring.

Exposure of aircraft maintenance technicians to organophosphates from hydraulic fluids and turbine oils: a pilot study.

Hydraulic fluids and turbine oils contain organophosphates like tricresyl phosphate isomers, triphenyl phosphate and tributyl phosphate from very small up to high percentages. The aim of this pilot study was to determine if aircraft maintenance technicians are exposed to relevant amounts of organophosphates. Dialkyl and diaryl phosphate metabolites of seven organophosphates were quantified in pre- and post-shift spot urine samples of technicians (N=5) by GC-MS/MS after solid phase extraction and derivatization. Pre- and post shift values of tributyl phosphate metabolites (dibutyl phosphate (DBP): median pre-shift: 12.5 μg/L, post-shift: 23.5 μg/L) and triphenyl phosphate metabolites (diphenyl phosphate (DPP): median pre-shift: 2.9 μg/L, post-shift: 3.5 μg/L) were statistically higher than in a control group from the general population (median DBP: <0.25 μg/L, median DPP: 0.5 μg/L). No tricresyl phosphate metabolites were detected. The aircraft maintenance technicians were occupationally exposed to tributyl and triphenyl phosphate but not to tricresyl phosphate, tri-(2-chloroethyl)- and tri-(2-chloropropyl)-phosphate. Further studies are necessary to collect information on sources, routes of uptake and varying exposures during different work tasks, evaluate possible health effects and to set up appropriate protective measures.

Biomonitoring of N-ethyl-2-pyrrolidone in automobile varnishers.

N-alkyl-2-pyrrolidones are important organic solvents for varnishes in industry. This study investigates exposure to N-ethyl-2-pyrrolidone (NEP) in varnishing of hard plastic components in an automobile plant. Two specific biomarkers of exposure, 5-hydroxy-N-ethyl-2-pyrrolidone (5-HNEP) and 2-hydroxy-N-ethylsuccinimide (2-HESI), were analyzed in urine samples of 14 workers. For this purpose, pre-shift, post-shift and next day pre-shift urine samples were collected midweek. Twelve workers performed regular work tasks (loading, wiping and packing), whereas two workers performed special work tasks including cleaning the sprayer system with organic solvents containing N-alkyl-2-pyrrolidones. Spot urine samples of nine non-exposed persons of the same plant served as controls. Median post-shift urinary levels of workers with regular work tasks (5-HNEP: 0.15 mg/L; 2-HESI: 0.19 mg/L) were ∼5-fold higher compared to the controls (0.03 mg/L each). Continuously increasing metabolite levels, from pre-shift via post-shift to pre-shift samples of the following day, were observed in particular for the two workers with the special working tasks. Maximum levels were 31.01 mg/L (5-HNEP) and 8.45 mg/L (2-HESI). No clear trend was evident for workers with regular working tasks. In summary, we were able to show that workers can be exposed to NEP during varnishing tasks in the automobile industry.

Reply to the letter of Anderson J entitled “Comment on Schindler, BK; Weiss, T; Schütze, A; et al. Occupational exposure of air crews to tricresyl phosphate isomers and organophosphate flame retardants after fume events, Arch Toxicol (2013) 87:645–648”

with creatinine concentrations above 3.0 g/L or below 0.3 g/L are considered as either highly concentrated or, in turn, diluted they are still suitable to identify exposure. Consequently, we decided not to exclude outlying values from data evaluation. However, a total number of 37 samples contained urinary creatinine levels above 3 g/L (2 samples) or below 0.3 g/L (35 samples). With respect to the presented statistical data of the organophosphate metabolites of tributyl (TBP), tris-(2-chloroethyl) (TCEP) and triphenyl (TPP) phosphates, there was no significant influence by the chosen approach. Ms. Anderson states that there are a total of ten isomers of TCP; four are meta and para isomers, and the remaining six are ortho isomers. This statement is misleading. Although TCP consists of ten isomers in total, there are six ortho, six meta and six para isomers. Three TCP isomers are “pure” isomers (o,o,o-, m,m,mand p,p,p-TCP). Seven isomers are “mixed” isomers, from which six contain two equal cresyl substituents (o,o,p-, o,o,m-, o,m,m-, m,m,p-, o,p,pand m,p,p-TCP) and one contains all three possible cresyl substituents (o,m,p-TCP). Consequently, each “mixed” isomer belongs to at least two groups of position isomers, e.g., o,o,p-TCP is an ortho isomer as well as a para isomer. According to common nomenclature, we used “o-TCP” for the sum of all six o-cresyl containing isomers (o,o,o-, o,o,m-, o,o,p-, o,m,m-, o,p,pand o,m,p-TCP). But o-TCP must not be mistaken for “ToCP” which is commonly used for o,o,o-TCP. Anyway, we agree with Ms. Andersons perception that “there is little if any ToCP in aviation oils.” Furthermore, there is very little o-TCP as already quoted in our paper (<0.01 % according to Craig and Barth 1999). In her letter to the editor, it is pointed out that “the three urinary metabolites alone [used in our survey] are insufficient to characterize onboard exposure to TCPs in aircraft In a letter to the editor, the industrial hygienist Ms. J. Anderson from the American Association of Flight Attendants-CWA (AFA) raised concerns in reference to our article (Schindler et al. 2013, DOI 10.1007/s00204-012-0978-0). We thank the editors of Archives of Toxicology for offering us the opportunity to reply to the remarks addressed by Ms. Anderson as follows: It is correct that the 332 pilots and flight attendants included in our survey represent 51 flights in total—the most extensive survey on aircrew exposure to tricresyl phosphates (TCP) so far. All subjects experienced a smell event (oil smell, stinky socks or other smells) which was considered to be serious enough to visit the airport physician directly after landing for a medical examination. Solely subjects issued with an accident notification for the responsible German statutory accident insurance (BG Verkehr) were included in our survey. The fact that in all cases at least several persons from the same flight took part in such medical examinations strengthens the self-reported statements of the participants and confirms that in each case there was a notable event in reality. However, the severity of the self-reported events cannot be assessed so far. The prime reason to conduct our survey was to answer the question whether there was a fume or smell eventrelated exposure to TCP or not. Even though urine samples