Biomarkers of exposure, effect, and susceptibility in workers exposed to nitrotoluenes.
Nitrotoluenes, such as 2-nitrotoluene, 2,4-dinitrotoluene (24DNT), and 26DNT, are carcinogenic in animal experiments. Humans are exposed to such chemicals in the workplace and in the environment. It is therefore important to develop methods to biomonitor people exposed to nitrotoluenes to prevent the potential harmful effects. For the present study, workers exposed to high levels of these chemicals were investigated. The external dose (air levels), the internal dose (urine metabolites), the biologically effective dose [hemoglobin (Hb) adducts and urine mutagenicity], and biological effects (chromosomal aberrations and health effects) were determined. Individual susceptibility was assessed by determining genetic polymorphisms of enzymes assumed to function in nitrotoluene metabolism, namely glutathione S-transferases (GSTM1, GSTT1, GSTP1), N-acetyltransferases (NAT1, NAT2), and sulfotransferases (SULT1A1, SULT1A2). The levels of urinary metabolites did not correlate with the air levels. The urinary mutagenicity levels determined in a subset of workers correlated with the levels of a benzylalcohol metabolite of DNT. The Hb-adducts correlated with the urine metabolites but not with the air levels. The frequency of chromosomal aberrations (gaps included) was increased (P < 0.05) in the exposed workers in comparison with a group of factory controls and correlated with the level of 24DNT Hb-adducts in young subjects (<31 years). The GSTM1-null genotype was significantly more prevalent in the controls than in the exposed group, which probably reflected an elevated susceptibility of the GSTM1-null genotype to adverse health effects of DNT exposure, such as nausea (odds ratio, 8.8; 95% confidence interval, 2.4-32.2). A statistically significant effect was seen for SULT1A2 genotype on a 24DNT Hb-adduct; GSTP1 genotype on a 2,4,6-trinitrotoluene Hb-adduct; and SULT1A1, SULT1A2, NAT1, GSTT1, and GSTP1 genotypes on chromosomal aberrations in the exposed workers.
Institute of Environmental and Occupational Toxicology, Casella Postale 108, 6780 Airolo, Switzerland. gabriele.sabbioni@bluewin.ch
Gabriele
G
Sabbioni
Christopher R
CR
Jones
Ovnair
O
Sepai
Ari
A
Hirvonen
Hannu
H
Norppa
Hilkka
H
Järventaus
Hansruedi
H
Glatt
Doreen
D
Pomplun
Huifang
H
Yan
Lance R
LR
Brooks
Sarah H
SH
Warren
David M
DM
Demarini
Yu-Ying
YY
Liu
D000328:Adult; D000395:Air Pollutants, Occupational / Q000009:adverse effects* / Q000032:analysis / Q000737:chemistry; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002617:Chemical Industry; D004198:Disease Susceptibility / Q000175:diagnosis*; D004784:Environmental Monitoring; D062665:Epidemiological Monitoring; D005260:Female; D005500:Follow-Up Studies; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D006403:Hematologic Tests; D006454:Hemoglobins / Q000032:analysis*; D006801:Humans; D008297:Male; D008452:Maximum Allowable Concentration; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014050:Toluene; D016482:Urinalysis; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000453:epidemiology
D000395:Air Pollutants, Occupational; D015415:Biomarkers; D005982:Glutathione Transferase; D006454:Hemoglobins; D014050:Toluene