M. Sorsa et al., ASSESSMENT OF ENVIRONMENTAL AND OCCUPATIONAL EXPOSURES TO BUTADIENE AS A MODEL FOR RISK-ESTIMATION OF PETROCHEMICAL EMISSIONS, Mutagenesis, 11(1), 1996, pp. 9-17
1,3-Butadiene (BD) is an important industrial chemical and environment
al contaminant, e.g. in urban air, traffic exhausts and tobacco smoke,
It has been shown to be genotoxic in vitro and in vivo and carcinogen
ic in rodents, mice being more sensitive than rats, The present study
confirmed this species difference, Using micronuclei in erythrocytes o
r bone marrow as a marker, mice responded at an effective level of 50
p.p.m., while the highest ineffective level in rats was 500 p.p.m. (in
halation of BD for 5 days), A dose-dependent increase in N-terminal va
line haemoglobin adducts was seen in both rats and mice, but the adduc
t levels in the latter species were on average five times higher, For
the first time, specific N-6-alkyldeoxyadenosine adducts were identifi
ed in lung and liver DNA of rats exposed to BD by inhalation, No signi
ficant difference in DNA adduct level was seen in lung tissue of rats
and mice at similar exposure levels, Occupational exposure levels to B
D in the European Process industry are variable, but generally <1 p.p.
m. Haemoglobin adduct levels were seen to be increased among the worke
r groups with higher potential exposure to BD (process work, bomb void
ing and repair duties) as compared with adduct levels in less exposed
workers in maintenance and the laboratory or control personnel, Howeve
r, the N-terminal valine haemoglobin adducts measured in the workers w
ere one to two orders of magnitude lower than extrapolated for the sam
e exposure dose in mice, In the same workers no exposure-related effec
ts were seen in the cytogenetic parametres studied, i.e. chromosomal a
berrations, sister chromatid exchanges or micronuclei in peripheral bl
ood lymphocytes, or in the Ras oncoprotein levels of plasma samples, T
he studies so far conducted suggest that human exposure at the levels
seen in the present day process industry can be documented at the biol
ogical dose level using haemoglobin adduct measurement, but not at the
biological effect level using cytogenetic biomarkers, In order to qua
ntitate the human genotoxic risk of BD exposure more work needs to be
done on the role of other active BD metabolites than 1,2-epoxy-3-buten
e and on the genetic polymorphisms controlling the variability of indi
vidual responses.