Opinion on the results of the Risk Assessment of: TOLUENE - Human health and Environment - CAS No.: 108-88-3 - EINECS No.: 203-625-9 - Report version : Final report March 2001 carried out in the framework of Council Regulation (EEC) 793/93 on the evaluation and control of the risks of existing substances1. Opinion expressed at the 24th CSTEE plenary meeting, Brussels, 12 June 2001
Terms of reference
In the context of
Regulation 793/93 (Existing
Substances Regulation), and on
the basis of the examination of
the Risk Assessment Report the
CSTEE is invited to examine the
following issues:
1. Does the CSTEE agree
with the conclusions of the
Risk Assessment Report?
2. If the CSTEE
disagrees with such
conclusions, the CSTEE is
invited to elaborate on the
reasons for this divergence of
opinion.
GENERAL COMMENTS
Toluene is a high
production volume (HPV)
substance. In 1995, the
estimated EU consumption was
2800 Ktonnes, including a
production of 2600 Ktonnes.
Once isolated from refinery
streams of crude oil, it is
used in a large number of
industrial branches and
consumer products such as in
closed system to manufacture
other chemicals and as a
solvent carrier in paints ,
thinners, adhesives, inks and
pharmaceuticals products and as
an additive in cosmetic
preparations. In addition,
toluene is also released
naturally e.g. by volcanoes and
forest fires.
Once emitted to the air, toluene combines with oxygen to form benzaldehyde and cresol. In addition, it contributes to the tropospheric formation of ozone. Some of these degradation and reaction products have been identified by the authors of the RAR but they have not been evaluated. It is the CSTEE opinion that they should be assessed. Last but not least, as also mentioned in the RAR, the production and use of gasoline (120,000 Ktonnes containing approximately 14,000 Ktonnes of toluene) has not been included in the present risk assessment of toluene. Given that the effects of toluene on humans and the environment are the same whatever its origin, the choice not to take into account the presence of toluene in gasoline makes the assessment of limited relevance to the actual impact of toluene on both the environment and the human health. Furthermore in one exposure scenario for consumers, filling gasoline at self-service gas station is considered. This is contradictory to the above mentioned statement to not consider toluene in gasoline, in addition, in this context, exposure of workers should be considered as well.
As a consequence, more
studies are needed indeed, to
assess the risk of toluene in
the air compartment for the
environment and the human
health. The CSTEE fully agrees
with the conclusion that, a) on
the basis of the available
data, b) considering some very
low MOS and in addition, due to
the predictable other risks
presented by toluene exposures
that are not taken into
consideration in the present
RAR, there is a need for
limiting the risk in both cases
in this compartment.
Because it is a HPV
chemical, and if one accepts
that gasoline should not be
considered in the RAR, the
consequences of the presence at
0.02% of impurities such as
benzene and xylene are relevant
and should be assessed.
With the exception of
the above remarks, both parts
(environment and human health)
of the RAR are of good quality
and the CSTEE generally agrees
with the conclusions. However,
it is noticed that the version
made available to the CSTEE
which is dated 2001, does not
include a number of relevant
studies issued in 1999 and
2000.
Environment
The CSTEE stress that in
the absence of TGD
recommendations, the RAR's
authors have presented a sound
evaluation of the available
information for addressing the
atmospheric compartment issue.
Because very few data are
available in order to assess
the effects on the air
compartment more studies are
needed.
Human Health
References to the
evaluations of toluene
published by the IARC in 1999,
and the Nordic Expert Group in
2000 should be included and
their content discussed.
Due to very low MOSs,
conclusion, that there is a
need for limiting the risk is
justified. In addition, the
need for more information is
further supported by the fact
that assessment of the risk of
toluene due to its extensive
use in gasoline as an
alternative to lead for
blending gasoline has not been
conducted in the present
report. Similarly, because
exposure of workers to toluene
is often associated with
exposure to other chemical
substances or physical
pollutants, synergistic or, at
least, additive effects which
have been reported in the
literature could have been
mentioned.
Human data as well as
studies in rodents provide
evidence of developmental
effects, i.e. lower birth
weight, delayed postnatal
development and developmental
neurotoxicity. The CSTEE agrees
with the assessor that the
compound is to be labelled
reproductive category 3, R63
(Possible risk of harm to the
unborn child).
The results of
neurotoxicity studies are
extensively discussed in the
report. The ototoxic effect is
well described. The CSTEE
supports the proposed
classification and labelling R
67 : vapours may cause
drowsiness and dizziness.
SPECIFIC COMMENTS
Environment
Exposure assessment
Toluene is emitted in
large quantities. Because it is
a volatile organic compound
emission is mostly to the air
compartment, however water
contamination is also possible
through discharges from
industrial sources. Toluene
binds loosely to soil and
therefore through leakage, may
enter groundwater. These
various possibilities have been
properly assessed in the
document.
Effects assessment
Even if difficulties to
test its biodegradation in
water arise from the volatility
of this substance, the
available results tend to
ascertain that toluene is
readily biodegradable. Due to
its Kow of 2.6 it has a low
bioaccumulation potential and
experimental results show a low
BCF and an elimination
half-life > 2. Altogether
these information demonstrate
that toluene is unlikely to
bioconcentrate in the aquatic
food chain.
As it is conceivable
with such a volatile substance,
the results from static tests
have not been considered for
effects assessment.
Effects of toluene to
the aquatic environment are
assessed on the basis of a
large number of data on algae,
crustaceans and fish (short and
long term). Many toxicity data
are produced in experimental
conditions suitable for this
highly volatile chemical
(flow-through, closed systems,
measured concentrations, etc).
Moreover, the variability of
experimental data within the
same taxonomic group is
relatively low and results are
generally in acceptable
agreement with QSAR
estimations.
Therefore, even if the
chemical could be problematic,
due to its physical-chemical
properties, toxicity data may
be assumed as enough reliable
and PNEC for the aquatic
environment is properly
calculated.
Although the TGD does
not include guidance for the
atmospheric compartment, the
RAR authors have presented the
available information and
proposed a case-specific
assessment. The assessment is
considered scientifically
sound. The CSTEE recognises the
effort and agrees with the
conclusions presented in the
risk assessment.
The derivation of the
PNECsoil organisms has been
done on the basis of actual
data and is supported by the
CSTEE.
Risk characterisation
A very detailed study of
the various PEC/PNEC ratio for
the different compartments has
been conducted in the report
and the conclusions are sound.
Even if, due to
degradation and volatility, the
half-life of toluene in the
aquatic environment is
relatively low, the high level
of emissions may produce
relatively high concentrations
at local level. Therefore,
PEC/PNEC values higher than 1
can be calculated in various
site-specific conditions.
The risk
characterisation combines
generic and specific
assessments when the
information is available. The
conclusions are considered
scientifically sound.
The CSTEE agrees with
conclusion iii (need for
limiting the risk) applied to
some site-specific production,
processing and downstream use
conditions.
The report states that
as regard indirect human
exposure via the food chain,
the contribution of toluene to
formation of ozone and other
harmful substances has not been
done on purpose. This is
questionable.
Human Health
Exposure assessment
This section on exposure
of workers and consumers is
especially well detailed and
conducted. Toluene is so widely
used that it is not surprising
that data are not available for
all toluene uses. Evaluation of
exposure to toluene in
photocopy centres have been
published (Stefaniak, AB et al.
2000, Envir. Res. 83: 162-173).
Effects assessment
Mutagenicity /
Genotoxicity
Toluene was not
mutagenic in bacterial and
mammalian cell gene mutation
and chromosomal aberration
assays in vitro. A few positive
results were observed at
cytotoxic concentrations. At
non-cytotoxic doses it did not
induce sister chromatid
exchanges, micronuclei or DNA
damage in vitro. It did not
induce DNA repair in various
bacteria nor gene conversions
in yeast and had no genotoxic
effects in Drosophila.
No cytogenetic changes
were seen in the bone marrow of
rodents and no DNA damage was
found in peripheral blood
cells, bone marrow and liver of
mice. Some positive results
were seen in studies where
benzene was present as a
contaminant. Toluene was not
mutagenic to the sperm of mice
in a dominant lethal test.
Equivocal results were
obtained in monitoring studies
with peripheral blood
lymphocytes from workers
co-exposed to toluene; no
sister chromatid exchanges,
however, were observed in
peripheral blood of volunteers
after prolonged exposure to 50
ppm.
The CSTEE agrees with
the assessor that toluene can
be considered to be
non-genotoxic.
Carcinogenicity
In F344 rats no increase
in the incidence of tumours was
found in a NTP 2-yr inhalation
study after exposures to 600
and 1200 ppm. No effects were
observed in another study after
2 years inhalation of 300 ppm;
however, as the MTD was not
achieved, this study is not
considered valid for the
assessment of a potential
carcinogenic effect.
In mice exposed for 2
years to 120, 600 and 1200 ppm,
non-malignant pituitary
adenomas in the pars intermedia
were found in all exposed
groups without a dose-response
relationship (1 adenoma each in
all groups of females and 1 in
the high dose male group).
An oral study in SD-rats
(Maltoni, 1983/5) where
haemolymphoreticular neoplasia
and "an increase in the total
number of malignant tumours"
were reported, was considered
invalid by the assessor due to
inadequate reporting (e.g. no
information on tumour types and
incidences, no historical
control data).
Toluene, used as a
vehicle in various dermal
carcinogenicity studies in
mice, did not induce a clear
increase in dermal tumours. One
skin-painting study (Primate
Research Institute, 1988)
showed skin irritation and
tumour development, the
difference in tumour incidence
was just below statistical
significance.
Human data do not show
an excess of tumours in
toluene-exposed workers.
Though there will be no
change in the conclusions, the
RAR should take account of the
latest IARC evaluation (1999).
In particular, there is
additional human
carcinogenicity data presented
in the IARC report that would
further support the conclusions
of the RAR.
The CSTEE agrees with
the assessor in that it cannot
be concluded that toluene is
carcinogenic.
Risk characterisation
Relevant exposure routes
are inhalation and dermal
exposures.
Mutagenicity
As toluene is considered
to be non-genotoxic, there is
no concern for this endpoint.
The CSTEE agrees with the
conclusion (ii) for this
endpoint for all scenarios
(workers, consumers).
Carcinogenicity
There is no concern for
carcinogenicity via the
inhalation route for workers
and consumers. Though there is
some uncertainty as to a
possible weak carcinogenic
effect of toluene via the
dermal route, conclusion (ii)
is reached as toluene is
labelled as irritating to skin
and therefore dermal exposure
is anticipated to be very low.
Consumers would only be exposed
intermittently to the
substance.
No risk characterisation
was performed for scenario U5
(filling gasoline at
self-service stations), as the
production and handling of
gasoline is not formally part
of the toluene risk assessment.
The CSTEE agree with the
conclusion (ii) for this
endpoint for all scenarios
(workers, consumers).
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1 Regulation 793/93
provides a systematic framework
for the evaluation of the risks
to human health and the
environment of those substances
if they are produced or
imported into the Community in
volumes above 10 tonnes per
year. The methods for carrying
out an in-depth Risk Assessment
at Community level are laid
down in Commission Regulation
(EC) 1488/94, which is
supported by a technical
guidance document.