Opinion on the results of the Risk Assessment of : Alkanes, C10-13, chloro {SCCP} 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 6th CSTEE plenary meeting, Brussels, 27 November 1998
CSTEE Opinion on the Risk Assessment of Short Chain Length Chlorinated Paraffins
Introduction
The CSTEE has been asked to give its
opinion on the risk assessment on short chain
length chlorinated paraffins produced within
the EU Programme for Existing Chemicals.
Chlorinated paraffin products are based on
polychlorinated alkanes and they are divided
into three categories depending on the carbon
chain length, short (C
10-C
13),
medium (C
14-C
17) and
long (C
20-C
30), and the
reviewed document deals with the first of
these categories. A working group within CSTEE
was established and it has reviewed the Final
draft (dated May 1998) of the risk assessment.
General substance information
This chapter deals with the identity and
properties of the chemicals. The commercial
products are extremely complex mixtures of
mainly n-alkanes with different chlorine
content. The many different compounds in the
products make the risk assessment difficult in
several ways, something which is obvious
already from the section on physico-chemical
properties. In the text the chlorinated
paraffins are described as hydrolytically
stable, in a table it is mentioned that the
water solubility is 0.15-0.47 mg/l "with
partial hydrolysis" with a reference to the
IUCLID database. In the CD-ROM version of this
base, however, the data for water solubility
are in the range 0 - 0.01 mg/l. Other
published data range from 0.00049 to 1.26
mg/l. Water solubility is an essential
parameter in this risk assessment and the
uncertainty in the data base will influence
the final result.
Large variation can also be found for other
parameters, such as vapour pressure and
partition coefficients. Different compounds in
the product may thus be distributed
differently in the environment and it is not
possible to find the same mixture everywhere.
This means that the test results for different
effects of the original product will not
necessarily be valid for the composition
present in a specific environmental
compartment. An important parameter for these
substances is the chlorine content. The
commercial short chain length products can
contain between 49 and 71% chlorine as an
average, which makes the heterogeneity of this
group still more pronounced. These
difficulties could have been more clearly
pointed out in the risk assessment document.
The report approaches these problems by a
straightforward application of the protocols
stated in the Technical Guidance Document, in
the same way that should be applied to a pure
chemical substance. Taking into account the
available information this is the only
possible solution, but clearly the high level
of uncertainty produced by this approach
and/or the specific application of the
Precautionary Principle (i.e. when taking out
a value from the range of physical-chemical
properties) should be clearly identified.
General information on exposure
Less than 15000 tonnes were, according to
the industry, produced in 1995 at two sites
within the EU. Nothing is said in the
assessment about export from or import to the
EU of these chemicals. The applications of
short chain length chlorinated paraffins are
described and the metal working sector is
using more than 70% of these products. Other
important applications are in rubber, paints,
sealants, leather and textiles.
Some qualifying statements in the text,
such as "is reported to be low", would have
gained strength if their sources had been
referenced.
Environmental exposure assessment
Emission factors for production of short
length chain chlorinated paraffins have been
taken from the Technical Guidance Document.
The values used are: 0 to air, 0.003 to
wastewater and 0.0001 to soil. A release
factor of 0.0001 to wastewater, referring
(indirectly) to unpublished data from
Gesellschaft Deutscher Chemiker, is also used
in the following calculations. Information,
not available to CSTEE, from the two
manufacturers in the EU indicate, however,
that the present emissions to waste water are
much lower than these figures and estimated to
be less than 9.9-26.7 kg/year.
In the estimation of emissions from
metalworking, the fate of short chain length
chlorinated paraffins on the swarf is a
special problem. About 90% of these are
re-used and it is claimed that the additives
are destroyed in this process. This is not
necessarily true as the swarf often is
pre-heated with hot air before added to the
melting process. These sites may thus be point
sources for chlorinated paraffins in the air.
There is also a possibility for the formation
of more toxic compounds from the chlorinated
paraffins in this heating process. Formation
of PCN and PCB have been reported in pyrolysis
experiments, a formation that also may take
place in the metal working operations.
The emissions from paint is, with reference
to a Canadian report, expected to be minimal.
However, in a recent report, which was not
available to the risk assessor, the emission
from surfaces with a paint containing short
chain length chlorinated paraffins was
measured. Extrapolation of the results to the
1150 tonnes used annually in paint within the
EU, gives a continental emission of about 9
tonnes. There are probably also contributions
from the surfaces painted last year and so on,
so this source may be significant.
Due to the many assumptions that have to be
made, the release estimates are subject to a
large uncertainty. The dominating source is
not unexpectedly the use in metal working with
emissions of about 1700 of the total 1800
tonnes per year in the EU.
The chemical analysis of the complex
chloroparaffin products is difficult and most
of the levels reported on environmental
concentrations are determined with a low
precision. Recently an elaborated method using
HRGC-ECNI-HRMS was described. This would be
able to give more exact results if pure
reference compounds were available.
In spite of the analytical difficulties
some levels of chlorinated paraffins have been
reported and in the following table some of
these are compared to the regional levels
predicted by the EUSES model. It can be seen
that the predictions after all are close to or
within the reported data sets.
Medium | PEC (EUSES)
regional | Measured
concentration | Unit |
Air |
12 |
No data |
ng/m3 |
Surface water |
0.33 |
0.05-4.0 |
µg/L |
Sediment |
1.2 |
0.05-15 |
mg/kg ww or dw |
Soil |
11 |
0.10 |
mg/kg ww or dw |
Fish |
2.6 |
0.025-3.3 |
mg/kg ww |
Meat |
0.15 |
0.032-0.088 |
mg/kg ww |
Recently high levels of short chain
chlorinated paraffins were reported in
biological samples from the Arctic indicating
that these chemicals are effectively
transported over long distances.
The EUSES model was also used to predict
local scenarios for the concentrations of
short chain length chlorinated paraffins in
different matrices. The outcome indicates high
concentrations in almost all matrices,
especially plant roots, which are expected to
contain more than g/kg concentrations. It is
obvious that this is wrong and it is also
explained as being the effect of unrealistic
partition coefficients being used for the
soil-root distribution. It is obvious that
EUSES has a problem with the highly lipophilic
compounds in these calculations.
Environmental effects assessment
The effect assessment clearly reflects the
lack of information for essential
environmental compartments such as sediments
and soils, as well as the difficulties in the
toxicological interpretation of some
toxicological studies.
The toxicity values selected in the report
and used for the risk assessment are
considered appropriate. Most (all) reported
acute toxicity values for aquatic organisms
are above the expected water solubility limit
(clear values for this essential parameter are
not available), however, these values are not
used in the final assessment.
The NOAEL of 166 ppm selected from the bird
reproduction study and its comparison with
mammalian toxicological information is also
well justified. However, the value is
restricted to a single mixture with a C
10-12,
58% Cl chlorinated paraffin. The avian
reproduction toxicity of other mixtures in
unknown.
Environmental risk characterisation
The methodology for PNEC derivation and the
application of uncertainty factors are in
agreement with the protocols stated in the TGD
for chemical substances.
Taking into account all mentioned problems,
the use of equilibrium partitioning for
sediment- and soil-dwelling organisms is
clearly not recommended, but as stated in the
report there is no other possibility with the
present level of information.
Human exposure assessment
No measured data for occupational health
exposures was found for the short chain length
chlorinated paraffins and therefore these were
modelled by the use of EASE. The outcome seems
reasonable, but it is surprising that people
working with manufacturing and formulation are
exposed to ten times higher dermal exposure
than those working in the metal working
sector.
Also consumer exposure had to be estimated.
It is claimed that chlorinated paraffins are
used infrequently in leather treatment as they
are relatively expensive. This may be argued,
as a recent investigation showed that the
emission from three different shoes all
contained chlorinated paraffins. The rest of
the estimates seem to be worst case types and
the most predominant sources found to be
leather clothing and metal working fluids.
The EUSES model outcome was used to predict
indirect exposure via the environment. The
extremely high levels predicted for root crops
indicate that this exposure route corresponds
to about 99% of the human intake. There are no
measured data for this matrix so the assessor
had to eliminate it by declaring it as
unrealistic. The CSTEE agrees with this
assumption, realising that we then accept that
this route does not contribute at all which is
unsatisfactory. The few measured data seem to
support the rest of the model outcome to some
extent.
Human health effects assessment
The report gives an acceptable presentation
of the available documentation on animal and
human toxicity of short-chain chlorinated
paraffins. These compounds are of very low
acute toxicity. Treatment with the chlorinated
paraffins may lead to skin irritation upon
repeated application, whereas they may cause
mild eye irritation. The paraffins do not
appear to induce skin sensitisation.
The liver and thyroid are target organs in
repeated dose studies with rats and mice. The
liver damage is associated with peroxisome
proliferation, whereas the thyroid effects are
correlated to altered thyroid hormone status
and glucuronyl transferase induction. Humans
would be much less sensitive to peroxisome
proliferation and thyroid hormone perturbation
than rats and mice.
In rats, neoplastic effects are seen in the
liver, the thyroid (females) and the kidneys
(males) as well as mononuclear cell leukaemia.
There was poor survival in this experiment. In
order to elucidate the mechanism underlying
the renal tumorigenic effect, there were
indications that a 58% chlorinated paraffin
caused hyaline droplet formation in male rats,
but this could not be confirmed by
immunocytochemical techniques. In mice,
neoplastic effects were again seen in the
liver and the thyroid (females). In male mice
there was a dose-related increase (control 0%,
low dose 6%, high dose 12%) in
alveolar/bronchiolar carcinomas. The report
states that no significance for human health
can be read into this pattern of results. This
statement is overly strong, it presumably
takes into account that the control animals in
this experiment did not show any evidence of
lung tumours, whereas the historical control
incidence was 5.8%.
There were no studies specifically
investigating effects on fertility. In rats,
signs of developmental toxicity were only seen
at maternally toxic doses.
It could have been mentioned that
chlorinated paraffins induce gap junctional
intercellular communication between cells in
culture.
Human risk characterisation
The report presents exposure estimates to
short-chain chlorinated paraffins for workers
(manufacture and use) and consumers
(inhalation and dermal exposure from use of
metal working fluids and leather and textile
clothing) as well as indirect exposure of man
via the environment. The CSTEE judges the
estimates presented in the report to be
reasonable.
The report suggests that the dose-related
increases in the incidence of adenomas and
carcinomas observed in the liver, thyroid and
kidney are not relevant to human health,
considering the likely underlying mechanisms
for these tumours. The CSTEE agrees that
peroxisome proliferation may be a plausible
mechanism for the liver tumours and that
altered thyroid hormone homeostasis may be a
plausible mechanism for the thyroid tumours,
respectively. One cannot totally discount the
possibility that such tumours could arise in
humans, but there would be very large
differences in carcinogenic sensitivity
towards the short-chain chlorinated paraffins
between rats and mice vs. humans with respect
to induction of such neoplasms. There is a
possibility that the kidney adenomas which
were observed, may be linked to the male
rat-specific phenomenon associated with
a
2u-microglobin accumulation in hyaline
droplets. However, hyaline droplet nephropathy
was not clearly demonstrated. Thus, the CSTEE
agrees with the view of the Specialised
Experts that the consequences of the finding
of kidney adenomas in male mice cannot be
ruled out. The CSTEE is in agreement with the
use of a NOAEL of 100 mg/kg/day for kidney
carcinogenicity.
It is the opinion of the CSTEE that the
finding of alveolar/bronchiolar carcinomas in
male mice should not totally be discounted, as
has been done in this report. A dose-related
trend was seen with the lowest effective dose
of 125 mg/kg/day. The underlying mechanism for
this finding is not known, although it should
be noted that the chlorinated paraffins are
not genotoxic. It is the view of CSTEE,
although the finding of lung tumours in male
mice may be of importance for humans, that it
would not substantially alter the outcome of
the risk characterisation.
CSTEE conclusions
The report, as a whole, is a good document
that tries to summarise the available
information on these substances/mixtures,
applying the principles set out by the
Technical Guidance Document to assess the
environmental risks associated to the life
cycle of the short chain length chlorinated
paraffins.
The CSTEE realises that the risk assessment
of the short chain length chlorinated
paraffins is a difficult task. The complex
nature of these products makes both exposure
and effect assessments complicated. The amount
and quality of data on the environmental
levels and effects of this group of compounds
are limited. This puts the models in focus and
the outcome of their estimates important. Some
shortcomings of EUSES are obvious and it may
be discussed if the risk assessment should
have been supported by a few measurements in
critical media.
In the exposure assessment the emissions
from goods containing short chain length
chlorinated paraffins are only discussed very
briefly. It has recently been realised that
several other persistent organic compounds
such as PCB and DEHP are emitted from a number
of different matrices. Even if the information
for chlorinated paraffins is very limited, it
may have been possible to extrapolate some
knowledge from other compounds.
The risk assessment can be considered as
the best possible solution for the
environmental effects assessment and risk
characterisation of these mixtures, taking
into account the available information. The
uncertainty in the process is higher than that
expected for pure chemicals, not only in
relation with the lack of ecotoxicological
information, but also with the problems
associated with the lack of characterisation
and comprehensive understanding of
physical-chemical vs. toxicological
relationships.
The generation of additional information is
considered essential to increase the
scientific basis of this assessment and to
reduce the level of uncertainty. Nevertheless,
the conclusion of potential unacceptable
environmental risks associated to the life
cycle of these chlorinated paraffins is
considered scientifically sound and in
agreement with an acceptable use of the
Precautionary Principle.
The CSTEE agrees with the conclusions of
the human risk characterisation that with
respect to workers there is at present no need
for further information and/or testing or for
risk reduction measures beyond those which are
being applied already. Furthermore, the use of
short-chain chlorinated paraffins poses no
significant risk for consumers or for man
exposed via the environment.
The main comments of the CSTEE can be
summarised in the following points:
- Products
based on chlorinated paraffins are very
complex and their properties (physical,
chemical and biological) will cover wide
ranges which makes an evaluation very
difficult which could have been more clearly
explained in the report
- Due to
difficult chemical analysis, exposure data
are scarce
- TGD has
been followed in most instances but a lower
release factor (provided by industry) was
used for production
- Emissions
from goods (e.g. shoes and paint) may have
been underestimated
- The EUSES
model seems to give acceptable results for
several compartments, but the uptake in e.g.
plant roots is probably a dramatic
overestimation resulting in the assumption
that root crops is responsible for the major
(99%) human intake of chlorinated paraffins
- The risks
identified in some local aquatic
environments is judged to be an appropriate
result of the risk assessment
- No
measured data for occupational health was
found and the outcome of the EASE model
surprisingly predict a ten times higher
exposure in the production of the compounds
than in their use in metal workshops
- The
report gives an acceptable presentation of
the available documentation on animal and
human toxicity, although it could have been
mentioned that these substances induce gap
junctional intercellular communication
between cells in culture
- The
finding of lung tumours in male mice may be
of importance for humans, but it would not
alter the outcome of the risk
characterisation