Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 202-476-7
CAS number: 96-09-3
of mutation in bacteria
several studies, styrene oxide was mutagenic in Salmonella typhimurium
strain TA100 without metabolic activation at concentrations ranging from
0.6 μg/mL to 12,000 μg/mL. Styrene oxide also was mutagenic in various
studies without metabolic activation in strain TA1530 at a concentration
of 768 μg/mL, strain TA104 at a concentration of 120 μg/mL, and strain
TA1535 at concentrations ranging from 0.6 μg/mL to 5000 μg/mL. The
mutagenic activity of styrene oxide was reduced by the presence of
glutathione or S9 liver homogenate. The R enantiomer of styrene oxide
was found to be more mutagenic in S. typhimurium strain TA100 than the S
enantiomer. In different studies, styrene oxide was not found to be
mutagenic in S. typhimurium strains TA1537, TA98, or TA97 with metabolic
activation when tested over a concentration range of 250 to 6,000 μg/mL.
It is remarkable that styrene oxide was predominantly tested positive in
S.typhimurium strains sensitive for base pair mutations, suggesting this
to be the predominant mechanism of mutagenicity.
styrene oxide was found to be mutagenic in Escherichia coli strain WP2
uvrA without metabolic activation at concentrations ranging from 480
μg/mL to 720 μg/mL. This suggests that a crosslinking effect is involved
in the mechanism of mutagenicity.
of mutation in yeasts
oxide caused mitotic gene conversions in Saccharomyces cerevisiae at a
concentration of 1,200 μg/mL without metabolic activation and induced
forward mutations in Schizosaccharomyces pombe at a concentration of 600
et al. 1976).
of mutation in mammalian cells
oxide induced a positive response in L5178Y (TK+/-) cells in the mouse
lymphoma assay at a concentration of 13.80 μg/mL without metabolic
activation. Metabolic activation reduced the mutagenic activity of
styrene oxide in this study (Amacher
and Turner 1982, cited in IARC 1994a).Styrene
oxide induced forward mutations at the hprt locus in Chinese hamster V79
cells at concentrations ranging from 100 μg/mL (Nishiet
al. 1984, cited in IARC 1994a) to
1,020 μg/mL without metabolic activation (Loprieno
et al. 1976, cited in IARC 1994a).
human T-lymphocytes treated with styrene oxide for 24 hours or 6 days at
concentrations of 0.2 to 0.4 mM, the maximal dose-dependent mutation
frequency at the hprt locus was10 to 20 mutants per 106 clonable cells.
This is approximately fourfold higher than background in human T
lymphocytes. No increase in hprt mutation frequency was seen at the
lowest concentration tested (0.05 mM) (Bastlova
et al. 1995).A
subsequent, similarly conducted study found that styrene oxide induced
mutations at the hprt locus at a frequency 3.6 to 4.8 times higher than
background in human T-lymphocytes (Bastlova
and Podlutsky 1996).
oxide induced an increased frequency of chromosomal aberrations without
metabolic activation in Chinese hamster V79 cells at a concentration of
cited in IARC 1994a)and
in human lymphocytes at concentrations ranging from 3.00 μg/mL to 80.00
and Sram 1985;(Linnainmaaet
al. 1978; Fabry et al 1978).
oxide induced increased micronucleus formation in cultured human cells
at a concentration of 80 μg/mL without metabolic activation(Linnainmaa
et al. 1978a,b, cited in IARC1994a).
mammalian cell cytogenetics (SCE) assay, primary lymphocyte cultures
were exposed to styrene oxide dissolved in DMSO at concentrations of 0,
10, 20, 50, 100, and 200 µM without metabolic activation. There was a
concentration related positive response of SCE induced over background
(Laffon B et al 2001).
oxide induced an increased frequency of sister chromatid exchanges (SCE)
without metabolic activation in Chinese hamster ovary (CHO) cells at a
concentration of 50.00 μg/mL (de
in cultured human lymphocytes at concentrations ranging from 1.00 μg/mL
to 8.4 μg/mL (Linnainmaa
et al. 1978).
of cultured human lymphocytes to a styrene oxide concentration of 100 μM
for 22, 36, 48, or 72 hours resulted in a six-fold increase in the
induction of SCE at 22 hours of exposure. However, there was a clear and
significant inverse relationship between exposure time and SCE frequency
(r = -0.9337, P = 0.0018). No relationship between the replication index
and the frequency of SCE was seen (r = -0.36, P > 0.05), although cell
viability was decreased 74% relative to the control(Chakrabartiet
study was conducted with cultured lymphocytes from human donors to
determine the influence of glutathione S-transferase M1 (GSTM1) genotype
on SCE induction by styrene oxide. In cultured human lymphocytes treated
with styrene oxide at concentrations of 50 or 150 μM for 48 hours, the
frequency of SCE was significantly increased (P < 0.001). The GSTM1
genotype had no influence on SCE induction by styrene oxide (Uuskula
et al. 1995).
subsequent, similarly conducted study to determine the influence of
glutathione S-transferase T1 (GSTT1) genotype on SCE induction by
styrene oxide also found increased frequency of SCE induction following
treatment with styrene oxide. In lymphocytes from individuals lacking
the GST1 gene, the mean numbers of SCE/cell were 1.7 and 1.4 times the
control values at styrene oxide concentration of 50 μM (2.78 and 4.83)
and 150 μM (13.74 and 18.98), respectively. In lymphocytes from
individuals with the GST1 gene, the mean numbers SCE were 2.78 and 13.74
times the control values at concentrations of 50 μM and 150 μM,
et al. 1998).
In a mammalian single cell gel (Comet) assay, primary lymphocyte
cultures were exposed to styrene oxide dissolved in DMSO at
concentrations of 0, 10, 20, 50, 100, and 200 µM without metabolic
activation. Tail length, percentage of DNA in the comet tail, and tail
moment are all increased in those cultures exposed to styrene oxide
concentrations equal to or higher than 50mM (Laffon B et al 2001, Laffon
B et al 2002).
oxide induced DNA single-strand breaks in human lymphocytes and calf
thymus cells in culture in a Comet assay. Styrene oxide was tested at
concentrations of 0.05 to 0.6 mM for periods ranging from 1 to 24 hours
(in a series of six experiments) and at concentrations of 0.1 or 0.2 mM
for 6 days (in a series of three experiments). Overall, styrene oxide
treatment decreased the survival of clonable cells. Styrene oxide formed
O6-guanine DNA adducts at a level of 1 to 4 adducts per 108 nucleotides
at concentrations of 0.2 to 0.6 mM in 24 hours. Styrene oxide -induced
single-strand DNA breaks occurred at all concentrations tested; the
breaks in DNA were repaired within 24 hours(Bastlova
et al. 1995).
oxide did not induce dominant lethal mutations or reciprocal
translocations in meiotic germ cells of male BALB/c mice administered
styrene oxide by intraperitoneal injection at a dose of 250 mg/kg (Fabry
et al. 1978).
oxide induced an increased frequency of sex-linked recessive lethal
melanogaster when administered as a vapor at a concentration of 200 ppm
mg/m3), six hours per day for four days, or orally at a dose of 200
mg/kg in the feed
hours without metabolic activation (Donner et al. 1979)
oxide administered by intraperitoneal injection at a dose of 250 mg/kg
had no effect on the frequency of micronuclei in polychromatic
erythrocytes of BALB/c mice (Fabry et al. 1978). Intraperitoneal
injection of 100, 200, or 400 mg/kg (single dose for evaluation of
peripheral blood, two injections for evaluation of bone marrow), did not
increase the number of micronuclei in erythrocytes of male ICR mice.
(Hagiwara et al, 1996)
The same result was obtained by Morita et al. (1997) after
intraperitoneal injection of 100, 200 and 400 mg/kg of styrene oxide to
male CD-1 mice.
treatment of CD-1 mice with 50, 500, or 1,000 mg/kg of styrene oxide
resulted in increased incidences of chromosomal aberrations (CA) in bone
marrow cells at all dose levels tested
(Lopreino et al. 1978, cited in IARC 1985, 1994a).
In vivo inhalation exposure to styrene oxide (25, 50,75 and 100
ppm) for 2, 4 or 20 days (25 ppm only) had no effects on chromosomal
aberration rates or sister chromatid exchange frequencies in the bone
marrow cells of Chinese hamsters. The only positive response in
aberration frequency was obtained when styrene oxide was injected in
lethal concentration (500 mg/kg body weight, i.p.) into the animal.
(Norppa et al, 1979).
Sinsheimer et al (1993) found, that only the S-enantiomer revealed
a statistically significant effect on chromosome aberrations and sister
chromatid exchanges if injected intraperitoneally at a dose of 100 mg/kg
to male CD-1 mice.
exposure of mice to SO vapor at a concentration of 50 ppm (245 mg/m3)
induced a slight increase in SCE in regenerating liver cells and
alveolar cells, but not in bone marrow cells (Conner et al. 1982, cited
in IARC 1985, 1994a). However, no increases in the incidence of SCE were
observed in the bone marrow cells of male Chinese hamsters exposed to SO
vapor by inhalation at concentrations of 25, 50, 75, or 100 ppm (122,
245, 368, or 490 mg/m3)
for 2, 4, and 21 (25 ppm only) days (Norppaet al.
blood lymphocytes, liver cells, and kidney cells obtained from mice
exposed to SO showed evidence of DNA damage (DNA single-strand breaks)
upon analysis with the alkaline version of the single cell gel
electrophoresis (Comet) assay. In the study, female C57BL/6 mice were
given intraperitoneal injections of SO (in corn oil) at doses of 50,
100, 150, or 200 mg/kg four to six hours before sacrifice. Increased DNA
damage, though not statistically significant (P < 0.05) in a one-tailed
Kolmogorov-Smirnov two sample test was observed in all cell types tested
from the 50-mg/kg dose level.
significant (P < 0.001) damage in DNA occurred in lymphocytes, liver,
and kidney cells at doses ≥ 100 mg/kg. Statistically significant
increases in the frequency of DNA
damage in the bone marrow were seen only at the two highest doses tested
injection of a single dose of 400 mg/kg styrene oxide to male mice
caused chromosome strand breaks in stomach, colon, liver, kidney,
bladder, lung, brain, and bone marrow in a single cell gel
electrophoresis (Comet) assay (Tsuda et al, 2000).
injection of a single dose of 400 mg/kg styrene oxide to male CD1 mice
resulted in a significant increase of chromosome strand breaks as shown
by the means of a comet assay. (Sasaki et al, 1997).
oxide caused single-strand DNA breaks in the liver, lung, kidney,
testis, and brain of male mice administered SO by intraperitoneal
injection at doses of 1.8 to 7.0 mM/kg (Walles and Orsen 1983, cited in
doses of 100 mg/kg of SO to male Swiss albino mice increased the
frequencies of gene conversion in Saccharomyces cerevisiae and of
forward mutations in Schizosaccharomyces pombe in a host-mediated assay
(Loprieno et al. 1976).
cited in RoC 11thedition, styrene oxide was mutagenic to
bacteria, yeast and insects; it induced chromosomal aberrations and
micronuclei in plants. The compound was mutagenic to mammalian cells in
induced DNA damage in mammalian cells both in
aberrations and sister chromatid exchanges in
several studies in mice and hamsters in
dominant lethal mutations, chromosomal aberrations, micronuclei or
sister chromatid exchanges were induced; however, in one study in mice,
styrene oxide induced chromosomal aberrations.
Negative data for in vivo heritable germ cell
mutagenicity in mammals are available from a dominant lethal test in
mice and a translocation assay in pre-meiotic male mice.
In-vivo studies were both positive and
negative. Styrene oxide induced DNA damage in mammalian cells in vivo
(positive UDS and Comet assay). In several studies in mice and hamsters
in vivo, no chromosomal aberrations, micronuclei or sister chromatid
exchanges were induced; however, in one study in mice, styrene oxide
induced chromosomal aberrations in bone marrow cells after gavage
application. Therefore there is some evidence that styrene oxide has the
potential to cause mutations to germ cells.
Styrene oxide was positive in various
in-vitro test systems. It was mutagenic to bacteria, yeast and insects;
it induced chromosomal aberrations and micronuclei in plants. The
compound was mutagenic to mammalian cells and induced DNA damage in
In conclusion positive results from in vivo
somatic cell mutagenicity tests in mammals, in combination with some
evidence that the substance has potential to cause mutations to germ
cells require classification for germ cell mutagenicity for styrene
oxide. Category 1B is justified according to GHS Regulation EC No
1272/2008 and category 2 (R46) according to directive 67/548/EEC.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Do not show this message again