Opinion on the results of the Risk Assessment of: METHACRYLIC ACID - Cas N° : 79-41-4 - EINECS N°: 201-204-4. Report version : Draft of 13.04.2000 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 19th CSTEE plenary meeting, Brussels, 9 November 2000.
Terms of reference
In the context of
Regulation793/93 (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.
Introduction
Methacrylic acid is used
as an internal and external
intermediate in the chemical
industry for the production of
methacrylic acid esters and as
monomer in different kinds of
polymers. The main use of
methacrylic acide is in the
preparation of ethyl
methacrylate and higher
homologues. Methacrylic acid is
also used in the preparation of
carboxylated polymers and
emulsion polymers for paints,
adhesives and textile
applications.
GENERAL COMMENTS
The environmental part
of the document is of good
quality. The CSTEE agrees with
the conclusion that there is no
need for further information
and that risk reduction
measures may be needed only in
particular conditions (use of
grouting agents and high
release via drainage water).
The CSTEE agrees with
the conclusion that there is a
need for limiting the risks
from short term inhalation
exposure in the chemical
industry and the intermittent
use of adhesives in the skilled
trade sector, although the
CSTEE questions some of the
scientific arguments on which
this conclusion is founded. The
CSTEE agrees with the
conclusions that there is at
present no need for further
information and/or testing with
respect to consumer exposure or
man indirectly exposured via
the environment.
SPECIFIC COMMENTS
Environment
Exposure assessment
PECs in all
environmental compartments
seems properly calculated,
using conservative worst case
scenarios in case of lack of
information. Nevertheless,
details of calculations are
reported in appendices, not
provided with the document.
Effect assessment
The toxicity of
methacrylic acid is relatively
low on aquatic animals. For
algae, there are some
controversial data,
nevertheless the reasons for
not considering a surprisingly
low figure is acceptable.
No data are available
for terrestrial animals,
besides mammals. Nevertheless,
due to many aspects of
environmental fate, methacrylic
acid can be considered as a low
concern chemical for
terrestrial (soil and air)
compartments.
Risk characterisation
Low or negligible risk
was calculated, with the
exception of some very specific
conditions. Risk for the
atmospheric compartment and for
secondary poisoning were not
calculated due to the low
persistence in the atmosphere
and to the negligible
bioaccumulation potential.
Considering the toxicological
and physical-chemical profile
of methacrylic acid, the use of
the equilibrium partitioning
method for the estimation of
PNEC for soil organisms is
acceptable.
The absorption
coefficient (Kp) for
methacrylic acid ranging from
0.076 to 0.24 l/kg indicates
that it has a high mobility
through soils and may leach to
groundwater. Thus, the
potential for leaching to
groundwater should be included
in the conclusions of the risk
assessment.
Human Health
Exposure assessment
Occupational:
Methacrylic acid is a chemical
intermediate which is further
processed to methacrylic
esters, homo- and co-polymers.
It is also used in reactive
adhesive preparations.
Methacrylate esters are used as
grouting agents for tunnelling
and sewer processes.
Methacrylic acid may be formed
from hydroxyethylesters in
alkaline environment.
Consumers: Polymers
manufactured with methacrylic
acid as co-monomer are used in
consumer products. When using
dispersion paints, lacquers and
2-component adhesives,
consumers may be exposed by the
inhalation route only to
residual monomer.
Indirect: There is a
possible intake of a total
daily dose of 0.15 m g
methacrylic acid/kg bw/day from
drinking water.
Effects assessment
There is very little
long-term toxicity data on
methacrylic acid. However, the
methyl ester of methacrylic
acid can be used as a model
substance in toxicological
studies, since methyl
methacrylate is rapidly
hydrolysed in the body to
methacrylic acid. Thus, results
obtained from the ester can be
regarded as worst case
assumptions as the ester is
likely to be absorbed more
readily and to a much higher
extent than the acid due to its
higher lipophilicity.
Methacrylic acid is a
corrosive substance/severe
irritant at the site of
application. On the other hand,
it has low acute toxicity.
There is no indication that
methacrylic acid has a
sensitising potential in guinea
pig tests or patch testing in
humans. However, it should be
noted that there is some
evidence for a sensitising
effect of methyl methacrylate
in experimental animals,
Further, there are reports of
allergic dermatitis and
allergic respiratory reactions
in humans.
Irritation of nasal
mucosa and degenerative lesions
of the olfactory epithelium are
seen in 90-day inhalation
studies with methacrylic acid
in rats and mice. The CSTEE
does not agree with the
conclusion that no clear-cut
experimental NOAEC can be
identified and that it is
"slightly below 20 ml/m3. The
report states that rats had
rhinitis from 20 ml/m3 exposure
and no lesions of the oflactory
epithelium at 300 ml/m3,
whereas mice had rhinitis and
lesions of the olfactory
epithelium at 300 ml/m3. It is
noted, however, that control
rats also had rhinitis in an
incidence comparable to rats in
the 20 and 100 ml/m3 groups.
Only in male F-344 rats was the
severity of rhinitis
dose-related, with an increase
at 300 ml/m3. The CSTEE would
regard 100 ml/m3 as the NOAEC
for the rat. The degeneration
of olfactory epithelium was
already present at 100 ml/m3 in
female mice (3/10 animals),
thogh not statistically
significant. Therefore, the
CSTEE would regard 20 ml/m3
NOAEC for the mouse. Overall, a
clear NOAEC of 20 ml/m3 has
been obtained for local
effects.
The CSTEE does not agree
with the statement that "It may
be assumed that the nasal
irritation threshold for
methacrylic acid will not
substantially change with
longer duration of exposure".
This fact is illustrated with
data on methyl methacrylate,
acrylic acid and methyl
acrylate. None of these
comparisons support the
assumption that there would be
no change of nasal irritation
threshold from subchronic to
chronic exposure:
- The methyl
methacrylate data show a NOAEL
of 500 ml/m3 (LOAEL 1000 ml/m3)
subchronic versus 25 ml/m3
(LOAEL 100 ml/m3) chronic for
the rat; howdver, the ester
data cannot be directly
compared to the acid
- For acrylic acid,
there is no chronic data to
compare to the subchronic data
- For methyl acrylate 20
month results (not 3 month) are
compared to 24 month results
Therefore, a decrease in
the irritation threshold for
chronic exposure is to be
expected as a worst-case
assumption as long as no
chronic toxicity study is
available.
The conclusions of the RAR state that the PBPK model (originally developed for acrylic acid and adopted to methacrylic acid) constructed for interspecies extrapolation, is not considered to be valid. Thus, the model has not been taken into account for deriving a NOAEC for humans, instead the NOAECs of the animal studies were used. The model for methacrylic acid has not been published, therefore the CSTEE cannot comment on the model and its reliability. However, the CSTEE understands that the model for acrylic acid was accepted by the US EPA (see minutes TM IV'99). The CSTEE would not put much weight in the argument of missing variability parameters for interindividual and interspecies toxicodynamic differences, as was done in the report. In view of the fact that mice and rats are obligatory nose-breathers, the comparability to humans regarding nasal effects is limited per se. There are even large differences in the irritation thresholds for rats and mice for acrylic acid and methacrylic acid, so the quantitative extrapolation to humans is in any case difficult. According to the above arguments, and the fact that always the most sensitive species is used for evaluating the margins of safety and since methacrylic acid does not require metabolic activation/inactivation, the CSTEE feels that most of the uncertainties in extrapolating stem from fundamental species differences and not from the human variability. Finally, the report itself does not address the above problems when evaluating the MOS values.
The CSTEE agrees with
the assumption that there is no
concern for carcinogenic
properties of methacrylic acid
based on structural
similarities with methyl
methacrylate for which there
are acceptable studies
available (the cited NTP study
cannot be found in the
reference list).
With respect to
genotoxicity, only a negative
bacterial gene mutation test is
available for methacrylic acid.
High concentrations of methyl
methacrylate caused chromosomal
aberrations and marginal
increases in sister chromatid
exchanges in mammalian cells in
culture.A bone marrow
micronucleus test and a
dominant lethal assay in mice
was negative with methyl
methacrylate, whereas a bone
marrow chromosomal aberration
test in rats were inconclusive.
The CSTEE considers that
methacrylic acid will not
express genotoxic activity
under in vivo conditions.
There are no data on
reproductive toxicity of
methacrylic acid. However,
since methyl methacrylate
(without a reproductive toxic
potential) is rapidly cleaved
to methacrylic acid, no concern
in relation to developmental
toxicity is assumed based on
teratogenicity studies with
methyl methacrylate. There is a
deficiency in that no data on
possible impairment of
fertility by methacrylic acid
(or methyl methacrylate) are
available. Given the low
margins of safety with respect
to methacrylic acid exposure in
a number of occupational
settings (vide infra), such
data are deemed necessary,
although there were no evidence
of changes in the reproductive
organs of rats after 90-days
inhalation. According to the
RAR, a 2-generation
reproductive study by
inhalation is being planned in
the US for the near future.
Risk characterisation
Workers: Overall, the
CSTEE agrees to the conclusion
iii) that there is a need for
limiting the risks based on
margins of safety of up to 3
for repeated inhalation
exposure. But as outlined
above, the supporting arguments
would in several instances be
contrary to those given in the
report. On the other hand, the
CSTEE does not agree with a
conclsion iii) for short or
intermediate exposure (Chapter
4.3.1), because in this case
the 3 month study is
representative for the exposure
scenario.
As methacrylic acid is a
corrosive substance, it would
be expected to produce sensory
irritation as well as local
lesions when inhaled. The
report focuses only on the
latter aspect, There are no
data on irritation in humans.
The RD50 as a measure of
sensory irritation in mice is
with 22000 ml/m3 surprisingly
high. At 4900 ml/m3 there was
only minor irritation in mice.
Therefore, it seems that the
discussed NOAEC of 20 ml/m3 is
also protective against sensory
irritation in humans.
Consumers: Only a
possibility for local effects
in the upper respiratory tract
from exposure to methacrylic
acid has been considered. Due
to similarity with methyl
methacrylate, no concern for
chronic effects or reproductive
toxicity is expressed
(conclusion ii)). The CSTEE
agrees to this conclusion.
Indirect exposure: No
concern is expressed for the
low exposure from drinking
water (conclusion ii)). The
CSTEE agrees to this conclusion
(possible revision, dependent
on data from grouting
episodes).
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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.