Opinion on the results of the Risk Assessment of: Acrylaldehyde, CAS N° : 107-02-8, EINECS N°: 203-453-4 carried out in the framework of Council Regulation (EEC) 793/93 on the evaluation and control of the risks of existing substances - Opinion expressed at the 15th CSTEE plenary meeting, Brussels, 5th of May 2000.
Terms of reference
The CSTEE on the basis
of the examination of each Risk
Assessment Report is invited to
examine the following issues:
1. Does the CSTEE agree with
the conclusions of each 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
ENVIRONMENT
The CSTEE agrees with
the conclusion of no need for
further information on aquatic
toxicity and for sediments.
However, the high value of the
local PEC/PENEC ratio for the
environment and micro-organisms
in treatment plants requires
more information on exposure
and if confirmed there is need
for measures to reduce exposure
in this compartment.
HUMAN HEALTH
The CSTEE disagrees with
the Risk Assessment Report
conclusion for consumers and
workers that no further testing
is needed. The CSTEE concludes
that the carcinogenic
properties, the irritative
properties and the inhalatory
sensitisation potential have
not been sufficiently
addressed.
Assessment factors are
applied to calculate a "minimal
MOS". This approach is not
generally accepted and has
already been criticised by the
CSTEE in the Risk Assessment
Reports of the glycolethers
2-(2-methoxyethoxy)ethanol and
2-(2-butoxyethoxy)ethanol.
SPECIFIC COMMENTS
ENVIRONMENT
The assessment is based
on a large set of short-term
toxicity data on freshwater and
marine organisms belonging to
all trophic levels of the
aquatic ecosystem (fish,
invertebrates, algae,
bacteria). Long term toxicity
data are available for
freshwater invertebrates.
Many data are of good
quality, performed with sound
methods and with analytical
control of concentrations. The
PNECwater calculation has been
performed with two procedures:
a factor of 10 applied to the
lowest long term NOEL and a
factor of 100 applied to the
more sensitive short term
figure. The PNECwater = 0.1
microg/L can be assumed as
stringent enough. The PNEC for
micro-organisms can also be
assumed as reliable.
The PEC/PNECwater is
lower than 1 (0.8), thus the
CSTEE can agree with the
conclusion of no need for data
on aquatic organisms.
On the contrary, the
higher value (2,9) for
micro-organisms indicates a
risk and requires a further
refined risk assessment with
more exposure data.
No data on sediment
dwelling organisms are
available and no attempts are
made for an estimation with the
equilibrium partitioning
method. The CSTEE can agree
with the hypothesis of a low
concern for sediments, but an
assessment on estimated values
could be performed.
The report identifies a
critical problem, the
phytotoxicity of acrylaldehyde
due to atmospheric emissions,
and their potential
environmental consequences. The
available information is used
to conduct a preliminary
assessment. The conclusions
should be fully supported, and
the additional information
requested is considered
essential for a proper
assessment of the environmental
risk of acrylaldehyde.
In order to better
evaluate the environmental
exposure import/export data
must be made available.
HUMAN HEALTH
Several aspects have not
been properly addressed in the
RAR.
1. Carcinogenicity
The conclusion that no valid dermal and inhalation studies exist is correct. The oral studies were negative. However, there is concern about a possible local carcinogenic effect in the respiratory system via inhalation. Acrylaldehyde is highly irritative, mutagenic in vitro and forms DNA-adducts. It can be postulated that, similarly to formaldehyde, carcinogenic effects may depend on local irritation and subsequent enhanced cell proliferation. No studies exist to address this problem. A carcinogenicity study by inhalation would clarify the situation; however, as the Risk Assessment Report concludes, it is not justifiable to require such a study due to the limited use and low exposure levels. Since irritation could play a significant role should acrylaldehyde be a respiratory carcinogen, a human study to determine the threshold for nasal irritation would be desirable. A transgenic mouse mutation study by inhalation is recommended in order to reveal the potential of acrylaldehyde to induce mutations in the respiratory system.
2. Inhalatory
sensitisation
On the basis of the
available information
acrylaldehyde is considered in
the Risk Assessment Report as a
skin sensitiser. In view of the
inhalatory exposure, the skin
sensitisation and the
reactivity the possibility of
inhalatory sensitisation should
be investigated.
3. Immunotoxicity
The relevance of the
decreased resistance to
bacterial infection following
inhalation exposure of mice at
low concentrations is to be
evaluated. Laboratory studies
in mice showed that
acrylaldehyde reduces the
pulmonary bactericidal
activity, data that should be
used for human risk assessment,
in particular as effects have
been reported at very low
exposure levels.
4. Workplace
Minimal MOSs of 3-6
(short-term exposure) and 16
(repeated exposure) are
proposed. There has not been a
consensus on minimal MOSs for
workers. In general, the SCOEL
(Scientific Committee on
Occupational Exposure Limits)
regards a MOS of 2 for acute
exposure and 2 to 5 for
long-term exposure starting
from NOELs as sufficient. The
calculated minimal MOSs by the
rapporteur are not
scientifically justified.
The calculations of
"Health-based Occupational
Reference Values" on the basis
of assessment factors are not
science based and should be
deleted.
The view that "the MOS
(of 50) between background
dietary intake and oral NOAEL
is low" is not supported. This
assumption is probably based on
the ADI-approach, which is, in
this instance however, not
scientifically founded.
5. Irritant upon
inhalation:
In the description of
the study by Weber-Tschopp et
al. the fact that also in the
control group higher scores for
eye irritation were reported
than those at 0.09 and 0.17
ml/m³ acrylaldehyde is missing.
The mean of these scores did
not reach the score 2, "a
little bit". Therefore, the
result of the study of Darley
et al. 1960, on which the LOEL
of 0.06 ml/m³ for eye
irritation is based, is
considered to be doubtful. The
SCOEL did not use the Darley
study, but used the
Weber-Tschopp study for
derivation of a STEL of 0.1
ml/m³. Moreover, the study of
Darley et al. is poorly
described in the Risk
Assessment Report (number of
subjects missing). Rather than
0.06 ml/m³, the NOEL for
subjective and objective eye
symptoms seems to be 0.17
ml/m³. The NOEL for all
symptoms is 0.09 ml/m³. This
would be consistent with the
setting of the SCOEL-STEL.
6. Odour threshold/irritant
effects
There is an obvious
discrepancy in the description
of odour thresholds and nasal
irritation thresholds in
humans: whereas the odour
threshold is 0.21-0.35 ml/m³
(Leonardos 1969; Plotnikova
1957), the nasal irritation
LOEL is reported to be 0.15
ml/m³ (Weber-Tschopp et al.
1977). It is hard to believe
that the irritation threshold
should be lower than the odour
threshold.
Annex 3, p. 138: The
inconsistency of the NL
approach to apply assessment
factors to evaluate MOS can be
seen from Tables 1 and 2. In
Table 1 a factor for
intra-species differences of 3
is applied, in Table 2 a factor
of 2.