PMID- 36717398
OWN - NLM
STAT- MEDLINE
DCOM- 20230321
LR  - 20230322
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 97
IP  - 4
DP  - 2023 Apr
TI  - Excretion kinetics of 1,3-dichlorobenzene and its urinary metabolites after 
      controlled airborne exposure in human volunteers.
PG  - 1033-1045
LID - 10.1007/s00204-023-03447-x [doi]
AB  - The solvent 1,3-dichlorobenzene (1,3-DCB) is formed during thermal decomposition 
      of the initiator 2,4-dichlorobenzoylperoxide in the production of silicone rubber 
      with potential exposure of production workers as shown in previous works. Despite 
      a threshold limit value (MAK value) of 2 ppm in air, there are currently no data 
      about the corresponding internal exposure that would allow for the derivation of 
      a biological limit value. In the present study, we have investigated the 
      absorption of 1,3-DCB and urinary kinetics of its metabolites in 10 human 
      volunteers after controlled inhalative exposure. Due to the strong odour of 
      1,3-DCB, a subjective evaluation of odour nuisance was also performed. Ten male 
      human volunteers (23-36 yrs.) were exposed 6 h/day to a concentration of 0.7 ppm 
      and 1.5 ppm in the Aachen workplace simulation laboratory (AWSL) with one week 
      between each experiment. In order to investigate potential dermal absorption, the 
      volunteers were exposed to 1.5 ppm wearing a suitable filter mask that prevented 
      inhalative exposure in a third exposure. 1,3-DCB in blood was measured after 3 
      and 6 h exposure and the urinary metabolites 3,5-dichlorocatechol (3,5-DCC), 
      2,4-dichlorophenol (2,4-DCP) and 3,5-dichlorophenol (3,5-DCP) were measured over 
      24 h after exposure via LC/MS/MS. There were clear dose-response relations for 
      all investigated parameters. The maximum excretion of the metabolites was reached 
      at the end of exposure and corresponded to 5.2 +/- 0.7 mg/g crea, 
      1.5 +/- 0.35 mg/g crea and 0.07 +/- 0.011 mg/g crea at 0.7 ppm and to 
      12.0 +/- 3 mg/g crea, 3.5 +/- 1.1 mg/g crea and 0.17 +/- 0.05 mg/g crea at 1.5 ppm for 
      3,5-DCC, 2,4-DCP and 3,5-DCP, respectively. The use of filter masks decreased the 
      internal exposure for about 85-90%, indicating substantial dermal absorption. 
      Odour perception did not show a dose-response, probably due to fast olfactory 
      adaption. The human study presented here provides an excellent basis for deriving 
      a biological limit value for 1,3-DCB.
CI  - (c) 2023. The Author(s).
FAU - Schettgen, T
AU  - Schettgen T
AUID- ORCID: 0000-0003-1256-1713
AD  - Institute for Occupational, Social and Environmental Medicine, Medical Faculty, 
      RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany. 
      tschettgen@ukaachen.de.
FAU - Bertram, J
AU  - Bertram J
AD  - Institute for Occupational, Social and Environmental Medicine, Medical Faculty, 
      RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
FAU - Krabbe, J
AU  - Krabbe J
AUID- ORCID: 0000-0003-4205-9783
AD  - Institute for Occupational, Social and Environmental Medicine, Medical Faculty, 
      RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
FAU - Christoforou, R
AU  - Christoforou R
AUID- ORCID: 0000-0003-0176-0434
AD  - Institute for Occupational, Social and Environmental Medicine, Medical Faculty, 
      RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
FAU - Schweiker, M
AU  - Schweiker M
AUID- ORCID: 0000-0003-3906-4688
AD  - Institute for Occupational, Social and Environmental Medicine, Medical Faculty, 
      RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
FAU - Esser, A
AU  - Esser A
AD  - Institute for Occupational, Social and Environmental Medicine, Medical Faculty, 
      RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
FAU - Moller, M
AU  - Moller M
AD  - Institute for Occupational, Social and Environmental Medicine, Medical Faculty, 
      RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
FAU - Ziegler, P
AU  - Ziegler P
AD  - Institute for Occupational, Social and Environmental Medicine, Medical Faculty, 
      RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
FAU - Kraus, T
AU  - Kraus T
AUID- ORCID: 0000-0001-9747-3776
AD  - Institute for Occupational, Social and Environmental Medicine, Medical Faculty, 
      RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
LA  - eng
GR  - SCHE 1623/2-1/Deutsche Forschungsgemeinschaft/
GR  - ZI 1553/5-1/Deutsche Forschungsgemeinschaft/
PT  - Journal Article
DEP - 20230130
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - FG32L88KO9 (3,5-dichlorophenol)
RN  - 75W0WNE5FP (1,3-dichlorobenzene)
RN  - 0 (Chlorophenols)
RN  - K18102WN1G (chlorobenzene)
SB  - IM
MH  - Humans
MH  - Male
MH  - Healthy Volunteers
MH  - Tandem Mass Spectrometry
MH  - *Chlorophenols
MH  - *Occupational Exposure/analysis
PMC - PMC10025240
OTO - NOTNLM
OT  - Dichlorocatechol
OT  - Dichlorphenol
OT  - Human biomonitoring
OT  - Silicone
OT  - Toxicokinetics
EDAT- 2023/01/31 06:00
MHDA- 2023/03/22 06:00
PMCR- 2023/01/30
CRDT- 2023/01/30 23:13
PHST- 2022/10/10 00:00 [received]
PHST- 2023/01/17 00:00 [accepted]
PHST- 2023/01/31 06:00 [pubmed]
PHST- 2023/03/22 06:00 [medline]
PHST- 2023/01/30 23:13 [entrez]
PHST- 2023/01/30 00:00 [pmc-release]
AID - 10.1007/s00204-023-03447-x [pii]
AID - 3447 [pii]
AID - 10.1007/s00204-023-03447-x [doi]
PST - ppublish
SO  - Arch Toxicol. 2023 Apr;97(4):1033-1045. doi: 10.1007/s00204-023-03447-x. Epub 
      2023 Jan 30.