Opinion on the results of the Risk Assessment of: 1,4-DIOXANE - CAS N° : 123-91-1 - EINECS N°: 204-661-8. Report version : Final Version, 5 November 1999 carried out in the framework of Council Regulation (EEC) 793/93 on the evaluation and control of the risks of existing substances 1. Opinion expressed at the 19th CSTEE plenary meeting, Brussels, 9 November 2000./br/>
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.
Introduction.
1,4-Dioxane is used as a
solvent in the production
processes of various
pharmaceuticals pesticides,
magnetic tapes, paper, cotton,
textile and adhesives. It is
also found in cosmetics
(shampoos and baby lotions). In
most cases, 1,4-dioxane will
not be present in the end
product. Its usage is slightly
but steadily decreasing since
several years.
There is a single site
of production within Europe
(2500t/y), no information is
available about possible import
volume (in 1990, the total
production volume in the US was
between 5000 and 9000 tons).
GENERAL COMMENTS.
The CSTEE agrees with
the general conclusions of the
RAR. However, this report
suffers from some
inconsistencies in the text. A
particular attention should be
paid to the reference section
which is to be carefully
checked as many references are
misquoted, incomplete,
difficult to get, out dated or
contain typing mistakes. This
is especially the case for the
Human health section.
The CSTEE draws
attention to that, review of
the report is hampered by the
hidden annexes; as an example,
calculations of releases are
based on confidential, not
communicated data which makes
them impossible to check!
There is no scientific
consensus about the
quantitative risk
characterisation methodology
that has been used in this
report by calculation of the
Margin Of Safety and comparing
this value to a minimal MOS.
Environment.
The release from use/end
products is neglected. If the
conclusions for magnetic tapes
and pharmaceuticals, and may be
pesticides, are acceptable,
products like glue and paint,
which certainly release their
solvents, have been neglected.
This could make a significant
difference and should be
re-assessed.
On page 19 the release
as a by-product in various
surfactants (mostly Alkyl Ether
Sulphates) is calculated to 3
tons/y in Germany and 0,7
tons/y in The Netherlands, but
in Table 3.1.1 the local
release is down to 4 g/d. This
is a site specific situation
indeed, but why have the
aggregated data not been used
even if the difference is not
expected to be large.
Due to lack of relevant
measurements, the comparison
between predicted and measured
data is difficult. The use of
unidentified measured data from
the Internet should be avoided.
1,4-Dioxane is not
readily degradable, this, taken
together with its easy capacity
to leach should be regarded as
a potential for contamination.
These points have not been
discussed in the report.
PEC and PNEC are
properly calculated.
Human Health.
The supporting evidence
for the R 66 proposal are not
clear from the text.
Consumers and workplace
exposures did not mention the
preferential uptake of
1,4-dioxane in the milk of
lactating women which should
lead, at least in the
workplace, to measures limiting
exposure of these women. This
together with the reasons put
forward in the RAR is an
additional matter for reaching
conclusion (iii) for workers.
Due to a low partition
coefficient, contamination of
the food chain by 1,4-dioxane
is likely to be very limited,
conversely, contamination of
drinking water is highly
relevant.
According to IARC,
1,4-dioxane is classified in
group 2B, however, this is
neither specified nor mentioned
in the document even though the
IARC evaluation has been done
at the same time as this
report.
SPECIFIC COMMENTS.
Environment.
On the basis of the
exposure scenarios used in the
RAR, conclusion of little if
any, risks to aquatic
ecosystems is acceptable.
As mentioned in the
document, there are no data
available as regard sediment
and sediment dwelling organisms
; however a low absorption
potential make this compartment
not of relevant concern.
The risk assessment for
the terrestrial (soil)
environment has been conducted
using the equilibrium
partitioning method due to the
lack of standardised tests on
soil dwelling organisms.
1,4-Dioxane is a liquid
miscible with water. Its
toxicological profile is
suggestive of a similar (and
very low) acute and chronic
toxicity to aquatic species
(fish, invertebrates and
algae). In addition other
studies indicate that
micro-organisms, terrestrial
invertebrates (contact toxicity
test on flesh fly) and
terrestrial plants (agar test
on Lactuca sativa) are not
particularly sensitive.
Therefore, the CSTEE considers
that the use of the equilibrium
partitioning method for the
PNEC soil derivation is
appropriate indeed.
The reference to
Denliger et al (1980) p35 is
not quoted in the reference
list.
Human Health.
In a simulated exposure
of a lactating woman to a
threshold limit value
concentration, in contrast to
15 other Volatile Organic
Compounds, 1,4-dioxane exceeded
the U.S. Environmental
Protection Agency non-cancer
drinking water ingestion rates
for children (Fisher, J. et al.
Lactational transfert of
volatile chemicals in breast
milk. Am. Ind. Hyg. Assoc. 58
(6) : 425-431.(1997); this
should be discussed.
An IARC evaluation of
the carcinogenic risk of
1,4-dioxane was ongoing during
drafting of this RAR and it has
been published the same year
(IARC Monographs on the
evaluation of the carcinogenic
risk of chemicals to humans.
1999, 71 : pp 589-602). This
evaluation which led to a
classification of 1,4-dioxane
in group 2B « possible
carcinogen » for human is not
quoted in the RAR. This is
unfortunate as some valuable
data which are available in the
IARC evaluation have not been
used in the RAR. However, in
the light of the EU criteria
for classification of
substances into Carc Cat. 3,
the CSTEE supports the EU
classification for the
following reasons that are
presented in the report :
- Carcinogenic effects
occurred only at high doses, at
which also organ toxicity
(liver, kidney, nose) was
observed, together with reduced
body weights and survival
rates.
- Based on the weight of
evidence CSTEE considers the
substance a non-genotoxic
compound
- The existence of a non
genotoxic mechanism of action
is proposed with the
implication of a practical
threshold above a certain dose
level (chronic stimulation of
cell proliferation): At low
dose 1,4-dioxane is rapidly
metabolized to
ß-hydroxyethoxyacetic acid
(HEAA) and 1,4-dioxane-2-one.
At higher doses (10 - 100 mg/kg
bw/d) this metabolism is
saturated, resulting in
decreased urinary excretion of
metabolites and increased
1,4-dioxane in expired air.
Also a shift in the ratio of
oxidation products of HEAA and
1,4-dioxane-2-one to the
possible reactive intermediate
products 1,4-dioxane-2-ol and
ß-hydroxyethoxy acetaldehyde is
proposed.
The work by Young et
al., 1978 cited p.64 and 65 as
an experimental study in the
rat is referenced in the list
as a human report; this should
be clarified.
In the report,
quantitative risk
characterisation is performed
by calculation of the MOS and
comparing this value to a
minimal MOS. This minimal MOS
has been established using
assessment factors which takes
into account the following :
- Inter- and
intraspecies differences
- experimental
conditions versus the
exposure pattern of the
worker,
- type of critical
effect,
- dose response
relationship,
- confidence in the data
base,
- correction for route
to route extrapolation.
However, there is
to-day, no scientific consensus
about both the use of such
assessment factors and this
concept.
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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.