Ulrich Müller-Herold, Marco Morosini, Olivier Schucht Abstract The present case study develops and applies a systematic approach to the precautionary pre-screening of xenobiotic organic chemicals with respect to large-scale environmental threats. It starts from scenarios for uncontrollable harm and identifies conditions for their occurrence that then are related to a set of amplifying factors, such as characteristic isotropic spatial range F. The amplifying factors related to a particular scenario are combined in a pre-screening filter. It is the amplifying factors that can transform a potential local damage into a large-scale threat. Controlling the amplifying factors means controlling the scope and range of the potential for damage. The threshold levels for the amplifying factors of each filter are fixed through recourse to historical and present-day reference chemicals so as to filter out as many as possible of the currently regulated environmental chemicals and to allow the economically important compounds that pose no large-scale environmental concern. The totality of filters, with each filter corresponding to a particular threat scenario, provides the filter series to be used in precautionary regulation. As a demonstration, the filter series is then applied to a group of nonreferential chemicals. The case study suggests that the filter series approach may serve as a starting point for precautionary assessment as a scientific method of its own.

1. Choosing Chemicals for
Precautionary Regulation: A Filter
Series Approach
U L R I C H M U¨ L L E R - H E R O L D , *
M A R C O M O R O S I N I , A N D
O L I V I E R S C H U C H T
Swiss Federal Institute of Technology Zurich (ETH),
8092 Zurich, Switzerland
The present case study develops and applies a systematic
approach to the precautionary pre-screening of xenobiotic
organic chemicals with respect to large-scale environmental
threats. It starts from scenarios for uncontrollable harm
and identifies conditions for their occurrence that then are
related to a set of amplifying factors, such as characteristic
isotropic spatial range F. The amplifying factors related
to a particular scenario are combined in a pre-screening
filter. It is the amplifying factors that can transform a potential
local damage into a large-scale threat. Controlling the
amplifying factors means controlling the scope and range
of the potential for damage. The threshold levels for the
amplifying factors of each filter are fixed through recourse
to historical and present-day reference chemicals so as
to filter out as many as possible of the currently regulated
environmental chemicals and to allow the economically
important compounds that pose no large-scale environmental
concern. The totality of filters, with each filter corresponding
to a particular threat scenario, provides the filter series
to be used in precautionary regulation. As a demonstration,
the filter series is then applied to a group of nonreferential
chemicals. The case study suggests that the filter
series approach may serve as a starting point for
precautionary assessment as a scientific method of its
own.
Introduction
On February 2, 2000, the European Commission informed
theinterestedpartiesofthemannerinwhichtheCommission
applied or intended to apply the precautionary principle (1).
In its attempts to compose a European policy on the
application of the precautionary principle, the Commission
has funded PrecauPri, a thematic network project conducted
under the auspices of the EC’s STRATA Programme. The
particular aim of the project was to develop a scientifically
sound, politically feasible, legally unambiguous, and demo-
cratically legitimated concept of precaution. The concept
should provide a policy framework for the implementation
of the precautionary principle in different risk areas and
ensure specificity and predictability for the various actors
involved. Within PrecauPri, the regulation of chemicals was
selectedasatestcaseforthedesignofappropriateprocedures
in the application of precautionary reasoning.
Although there is no single authoritative definition of the
precautionary principle, in many of its various formulations
four dimensions can be identified (2): (i) a dimension of
threat; (ii) a dimension of ignorance, concerning the limits
ofscientificknowledge;(iii)adimensionofaction,concerning
the response to the threat; and (iv) a dimension of command,
concerning the way in which the action is prescribed. By
“threat”, in this context, is meant one or another undesired
state of the world. “Ignorance” has a wide range of different
meanings, from milder forms of uncertainty about prob-
abilities or incomplete proof of supposed cause-and-effect
relations to the most extreme form of “ignorance of igno-
rance” where the kind of possible unwanted effects itself is
unknown (3). This last possibility typically applies to
environmental chemicals, where the complete spectrum of
possible negative effects is but insufficiently known.
However, even if negative effectsssuch as plant toxicity,
thinning of eggshells of sea eagles, endocrine disruption,
weakening of the immune systemsare largely unknown,
there may be sufficient knowledge of so-called amplifying
factors that can serve as a basis for precautionary action. It
is the amplifying factors that transform, for example, toxicity
into a large-scale environmental threat. Toxicity, by its very
nature, is first of all a local phenomenonsone organism is
exposed to a possibly toxic dose of a substance at a given
instance and a given place. However, amplifying factors such
as mobility, bioaccumulation, and persistence of a substance
can transform its toxicity into a nonlocal, possibly global
large-scale problem. The amplifying factors then generate
the large-scale nature of the respective management prob-
lems. If, eventually, perhaps even a long time after release,
an apparently innocuous persistent and mobile chemical
has negative biological effects, it is impossible to eliminate
it from the environment. The resulting situation would be
uncontrollable because even immediate phasing out may
not ameliorate the situation quickly enough for some species.
The PCBs and the extinction of the European otter (Lutra
lutra) can be regarded as an example of this behavior (4).
This leads to the central idea of precautionary regulation.
It considers large-scale threats arising from uncontrollable
situations in case of eventually discovered adverse effects.
It is a regulation based on reliable scientific knowledge of
amplifying factors but prior to knowledge of adverse effects.
It is tailored to situations where no immediate action would
solve the problem if any novel adverse effect is discovered.
Although persistence is an amplifying factor of this kind,
one has to recognize that the long-term presence of a
chemical or product alone does not lead to possibly
uncontrollable environmental situations of said type. (This
can be seen from the examples of concrete, bitumen, plastics,
etc.) Only in combination with other amplifying factors, such
as mobility, does persistence play a significant role as
indicatorforlarge-scalechemicalthreats.Theseobservations
are used to propose a general approach to precautionary
regulation by controlling amplifying factors of adverse effects
instead of controlling adverse end points directly (5).
Precaution and Chemical Risk Assessment
The current practice of chemical risk assessment centers
around the identification of risks for human health and the
environment (6). The detailed outcome of the assessment
procedure then leads to specific regulations depending on
exposure, tonnage, and use pattern. The present case study
aims at complementing this procedure by a precautionary
pre-screening stage (Figure 1).
Regulations on the basis of precautionary assessment are
necessarily controversial, mainly due to the dimension of
ignorance and uncertainty. Since stakeholders in public
* Corresponding author phone: +41-44-6324403; fax: +41-44-
6331136; e-mail: mueller-herold@env.ethz.ch.
Environ. Sci. Technol. 2005, 39, 683-691
10.1021/es049241n CCC: $30.25 © 2005 American Chemical Society VOL. 39, NO. 3, 2005 / ENVIRONMENTAL SCIENCE & TECHNOLOGY 9 683
Published on Web 12/24/2004

2. debates or in courts of law are not experts in this field,
arguments and methods have to be transparent, simple, and
intuitivesin addition to being scientifically correct. This
excludes black-box-type computer calculations, highbrow
mathematics, and esoteric chemical details. Furthermore,
measures should concentrate on serious threats where “wait-
and-see” strategies cannot be justified. The history of the
MontrealProtocolonozone-depletingsubstancesshowsthat
restrictions on the basis of precautionary arguments can be
accepted even by stakeholders with opposite interests if the
threats are important and action is urgent.
Along these lines, we present a filter series procedure for
precautionary pre-screeening of organic chemicals with
respect to large-scale environmental threats. Each filter is
designed to screen for one particular threat scenario (which
helps intuition). Accordingly, there is a one-to-one cor-
respondence between threat scenarios and filters. The
amplifying factors entering the filters are calculated by
inserting measurable physicochemical constants into simple
and theoretically sound formulas (transparence), and the
calibration of the filters makes optimal use of historical
experience with environmental chemicals (relevance). The
overall outcome is independent of the filter ordering, and
new threat scenarios can be taken into account without
questioning earlier results that led to the elimination of
suspect compounds (upward compatibility). Substances not
filtered out by any of the filters continue on to standard
chemical assessment.
Large-Scale Threat Scenarios and Filters
Originally, the PrecauPri case study provided a four-
membered filter series for pre-screening: Pandora, Cold
Condensation, Transformation Pandora, and Bioaccumu-
lation (Figure 2). The Pandora scenario relates to enduring
ubiquityofenvironmentalchemicals.TheColdCondensation
or Cold Trap scenario considers the selective accumulation
of environmental chemicals in low temperature areas, first
of all in the polar regions. In addition to a domain of direct
impact, environmental chemicals have a second, naturally
more extended domain of influence due to their transforma-
tion products in the environment. The Transformation
Pandora scenario, accordingly, deals with the enduring
ubiquity of these secondary compounds, using the results of
Quartier and Mu¨ller-Herold (7) and of Fenner et al. (8). The
threat scenario related to Bioaccumulation is given through
the possibility of substances to have adverse effects on living
organisms even if their concentration in the oceans, lakes,
rivers, or in the atmosphere is extremely low. If a bioaccu-
mulating and persistent chemical has negative biological
effects, it is impossible to eliminate it from the biosphere,
and the resulting situation is as uncontrollable as in the
Pandora scenario.
Due to the data situation, the present case study restricts
itselftoacombinationofonlyPandoraandBioaccumulation.
(An introduction to Transformation Pandora and Cold Trap
is provided in Section 5 of the Supporting Information, and
an example of a three-filter sequence including Transforma-
tion Pandora is provided in Section 6 of the Supporting
Information.)
Pandora. The Pandora scenario is named after the Greek
myth of Pandora’s box, which held all evils and complaints.
When the box was opened, its contents were unleashed upon
the world, causing irreversible harm. The enduring ubiquity
of persistent organic pollutants (POPs) is regarded as the
epitome of the Pandora scenario (9). For the construction of
a related filter, one observes that the Pandora scenario is
essentially due to the interplay of mobility and longevity.
The potential for mobility and longevity is expressed by two
proxy measures: characteristic isotropic spatial (CIS) range
(F) and characteristic isotropic global (CIG) half-life (τ).
Characteristic isotropic spatial (CIS) range F is the typical
distance a molecule would travel before degradationsunder
earth-like but spatially isotropic conditions where concen-
trations quickly equilibrate between the atmosphere, the
surface layer of the oceans, and the upper layer of the soil
(see Appendix).
Characteristicisotropicglobal(CIG)half-life τisthetypical
overall lifetime of a molecule under conditions as for F (see
Appendix). (The joint use of spatial range and persistence in
chemical assessment goes back to Scheringer and Berg (10).
(For details of the subject and its history, see Scheringer (11)
and references therein.)
Bioaccumulation.Bioaccumulation(12)isaphenomenon
combining bioconcentration and biomagnification. Biocon-
centration relates to the partition of a chemical between an
organism and a surrounding inorganic medium (e.g., leaves/
air, fish/water). Biomagnification denotes the heterotrophic
enhancement of concentration in subsequent elements of
the food chain (grass/cow, cow/man).
As fat tissue is the relevant storage medium in living
organisms and as octanol is the chemical proxy usually
representingorganismicfat,bioconcentrationisrelatedeither
to a chemical’s octanol-water partition coefficient (Kow) or
to its octanol-air partition coefficient (Koa ) Kow/K′), with K′
) KH/RT being the chemical’s dimensionless Henry’s law
constant. Kow is a direct measure for bioaccumulation from
water into aquatic species, whereas Koa is a direct measure
for bioaccumulation into plants from air. In order not to
classify the Montreal gases as bioaccumulatingswhich they
definitely are notsKoa is preferred to Kow. (For details of this
choice, see Section 8.1 of the Supporting Information.)
Analogous to the Pandora scenario, the Bioaccumulation
filter is based on two amplifying factors: a combination of
highKoa valuesandincreasedglobalcharacteristicpersistence
(τ). (To bioaccumulate, a chemical has to survive a minimal
period of time before degradation.)
Filters and Filter Series
In the case study, the individual filters were realized as two-
parameter classification schemes with three outcomes:
“green” (“unconditional clearance”), “yellow” (“conditional
clearance”), and “red” (“no clearance”). For filters based on
FIGURE 1. Extended chemical assessment including pre-screening.
Achemicalnotscreenedoutbyoneofthefiltersproceedstostandard
chemical assessment.
FIGURE 2. Scheme of a series of four filters for pre-screening with
respect to large-scale environmental impact.
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3. two parameters x and yswith each parameter x or y having
the grades high/medium/lowsthe outcomes are defined
using these grades of the two parameters (Figure 3): green
(medium/low, low/low, low/medium); yellow (high/low,
medium/medium, low/high); red (high/medium, high/high,
medium/high).
The calibration of filters now consists of defining the
parametergradesleadingtothefilteroutcomesgreen,yellow,
and red. For two-parameter filters with three grades for each
parameter, one has to find limiting values separating low/
medium and medium/high for the respective filter param-
eters. If x and y denote the two parameters and xlm, ylm, xmh,
and ymh denote the corresponding limiting valuesswhere
xlm signifies a limiting value separating low values of x from
mediumonesandxmh isthecorrespondingmarkattheborder
between medium and high, etc.sthen the two points, (xlm,
ylm) and (xmh, ymh), define a partition of the x-y plane into
the required nine rectangular filter domains (see Figure 3),
which then are grouped into the three filter scores: green
(low/low, low/medium, medium/low), yellow (low/high,
high/low, medium/medium), and red (medium/high, high/
medium, high/high).
Inthecaseofaseriesofseveralfilters,theaboveprocedure
applies to each filter separately. The outcome of the series
as a whole then consists of a list of results for the individual
filters that subsequently have to be combined to an overall
result. This is performed along the following rules:
1. A substance classified as red by at least one filter
definitively constitutes a serious threat, which triggers
prevention. Such a chemical should be eliminated (with the
possible exception of “life-saving” pharmaceuticals or some
intermediates in industrial synthesis if contained under strict
safety standards).
2. Green results in all filters open the way to standard
chemical risk assessment. Such a result implies that the
substance is inconspicuous with respect to the threat
scenarios under consideration.
3. The intermediate cases (i.e., yellow results with or
without green scores) trigger a variety of procedures,
depending on the intended modes of use.
Rule 1 is the epitome of the precautionary approach,
whereas rule 2 opens the door to current practice. Rule 3
may result in requirements relating to chemical modification
(pesticides), restriction of production volume (consumer
products),orcontainmentcharges(intermediatesinchemical
synthesis), etc.
Case Study with Two Filters: Pandora and
Bioaccumulation
The essential difference between one single filter and a series
of filters is most easily illustrated by a combination of only
two filters: A precarious chemical should get a red score by
at least one of the filters. For precautionary regulation, there
is no need to receive a red score from more than one filter
since one red is regarded as a sufficient condition for
preventive measures. Since this distinction becomes trivial
in the case of one single filter, one needs at least two filters
for its nontrivial demonstration. Additionally, for obvious
reasons it has to be required that chemicals known as
inconspicuous should be stopped by none of the filters.
Asanexample,theamplifyingfactorsforboththePandora
filter and the Bioaccumulation filter were calculated. For the
calculation of characteristic isotropic spatial (CIS) range,
characteristic isotropic global (CIG) half-life, and octanol-
air partition coefficient (Koa) of a chemical, four substance-
related input data are needed (see Appendix): KH, Henry’s
law constant (air-water partition coefficient); Kow, octanol-
water partition coefficient (descriptor of lipophilicity); ka,
degradation rate constant in air; and kw, degradation rate
constant in water.
On the basis of the data of the top 35 U.S. High Production
Volume (organic) Compounds (HPVCs) (13) as paradigmatic
examples for chemicals not posing large-scale threats in the
environment and a relevant selection of 43 Montreal/Kyoto/
Stockholm compounds as paradigmatic examples for pre-
carious chemicals, the output parameters τ, F, and Koa were
calculated. The results are shown in Figures 4 and 5. It turns
out that in both scenarios the regulated compounds are well
separated from the HPVCs.
Filter Calibration and Filtering Results
Following the Filters and Filter Series section, one now has
to find the limiting values defining the filter grades for
Pandora and Bioaccumulation (which at the same time
corresponds to the specification of a level of protection).
Generally, limiting values are directly discussed in purely
scientific terms. Along these lines, one could try to fix the
filter calibration directly. However, the history of medical
and environmental threshold values shows that the way to
firm, lasting agreements is long and troublesome. To come
to a first meaningful estimate, we look at limiting values
optimally separating the two sets of reference substancess
the 35 U.S. HPVCs and the 43 chemicals of the Montreal/
FIGURE 3. Two-parameter filter with three grades.
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4. Kyoto/Stockholm group. Though rather indirectly, economi-
cal and political facts thus enter calibration and complement
(pure) science. Algorithms solving the separation problem
are the first Jarimo Procedure (Section 3 of the Supporting
Information), its refinements (14), and the geometrical
method by Schucht (15). The first Jarimo algorithm gives the
following separating values: Pandora: F: low/medium, 340
km; medium/high, 8600 km. τ: low/medium, 9 d; medium/
high: 50 d. Bioaccumulation: log Koa: low/medium, 3.27;
medium/high, 6.89. τ: low/medium, 6.31 d; medium/high,
641 d. As the filters are calibrated independently, it is hardly
surprising that the threshold value for high persistence is
different for Pandora (50 d) and Bioaccumulation (641 d).
With respect to the large-scale threats in question, there
are four basic outcomes. A substance can be
classified as (a) inconspicuous (two green scores) when being
inconspicuous(HPVCs);(b)inconspicuous(twogreenscores)
though being precarious (Montreal/Kyoto, etc.); (c) precari-
ous (at least one red score) though being inconspicuous
(HPVCs); or (d) precarious (at least one red score) when being
precarious (Montreal/Kyoto, etc.).
With the above calibration, the pre-screening filtering
completely reproduces the present situation (see Table 1;
the details are contained in Tables 1 and 2 of the Supporting
Information): no HPVC received a red score (which would
stop it), and most of them (80%) even were given two green
scores (unconditional clearance). Only seven substances
(20%) received a yellow score (conditional clearance),
indicating that closer examination should follow. Concur-
rently, each of the universally itemized Montreal/Kyoto/
FIGURE 4. Outcome of the Pandora amplifying factors τ (characteristic isotropic global half-life) and G (characteristic isotropic spatial
range) for the HPVCs and a relevant selection of the Montreal/Kyoto/Stockholm chemicals. The regulated compounds are well separated
from the HPVCs. The dotted line gives the theoretical maximum spatial range at given half-life, obtained by combining CIG half-life with
maximal mobility (i.e., eddy diffusion in air). Realistic (i.e., lower) mobility in water and soil leads to points exclusively at the left of the
dotted line.
FIGURE 5. Outcome of the Bioaccumulation amplifying factors Koa (octanol-air partition coefficient) and CIG half-life τ for the HPVCs
and a relevant selection of the Montreal/Kyoto/Stockholm chemicals. The Montreal/Kyoto/Stockholm chemicals are well separated from
the HPVCs. (References and details of the data selection are given in Sections 2 and 4 of the Supporting Information.)
686 9 ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 39, NO. 3, 2005

5. Stockholm chemicals was given one or two red scores (no
clearance), completely in line with the outcome of the above
conferences.
The calibration for the two filters was validated separately
by the repeated 2-fold cross-validation method (16). For this
purpose the set of reference chemicals was randomly divided
into two approximately equal-size halves, referred to as the
training set and the test set. The filter at hand was then
calibrated using the chemicals in the training set as the
reference chemicals. The desired statistics were calculated
by filtering the chemicals of the test set using the filter
calibration obtained with the training set. For both filters,
the 2-fold cross-validation was repeated N ) 5 times, each
time with a different randomly generated training set and
test set. Within each run, the following statistics for the test
set were calculated: (a) number of HPVCs in green; (b)
numberofHPVCsinred;(c)numberofregulatedcompounds
(Montreal, etc.) in green; and (d) number of regulated
compounds (Montreal, etc.) in red. Table 2 shows the results
of the five test runs.
The repeated 2-fold cross-validation method was chosen
due to the small size of the set of reference data. By dividing
the set of reference chemicals in two equal size halves, we
obtain the largest simultaneous training set and test set.
Repeating the cross-validation several times compensates
for the small size of the data set. (As for the question whether
equivalent results can be achieved using a so-called Boolean
OR operation, see Section 8.2 of the Supporting Information.)
Special Chemicals of Environmental Interest
Aside from the two sets of referential chemicals, a selection
ofchemicalswasputtogethershowingsomeapriorievidence
of persistence, bioaccumulation or long-range transport.
Some of these special chemicals might be regulated on
nationallevels.Asanapplicationofthefilterseriestechnique,
they were submitted to precautionary pre-screening. The
results are shown in Table 3 and Figures 6 and 7. The input
parameters of these chemicals and the calculated values of
the amplifying factors are shown in Table 4.
The three stereoisomers R-HCH, β-HCH, and γ-HCH
(lindane) of the insecticide hexachlorocyclohexane are the
major components of the once widely used so-called
“technical HCH” (benzene hydrochloride, BHC). They are
also the most frequently detected HCH isomers in environ-
mental samples and in human fat and milk. Technical HCH
is now banned in most industrialized countries, where in
contrast lindane, the only insecticidal isomer, is used as an
almost pure substance. In the United States, the production
of lindane ceased in 1976. R-HCH and γ-HCH are almost
ubiquitous in environmental samples from every continent,
including polar and pristine regions (17). The three chemicals
received a red score both in the Pandora and the Bioaccu-
mulation filters. Although they are widely considered as POPs
in scientific literature, the HCHs are not included in the
Stockholm Convention.
Endosulfan is a polychlorinated cyclodiene insecticide
whose use is permitted in most countries because of its rel-
atively rapid degradation in air and water and because of its
lower tendency to bioaccumulate if compared to DDT or the
HCHs. It passes both filters, receiving a green score from
both the Pandora and the Bioaccumulation filters. For an
extended appraisal of endosulfan, its transformation pro-
ductssendosulfan diol, endosulfan sulfate, and endosulfan
endolactonesshould also be considered (i.e., endosulfan
itself should be sent through the Transformation Pandora
filter). At present, however, physicochemical input param-
FIGURE 6. Outcome of the Pandora parameters τ (characteristic isotropic global half-life) and G (characteristic isotropic spatial range)
for 11 chemicals of special interest (see Table 3). The dotted straight lines denote the limiting values of 9 and 50 days, respectively, for
CIG half-life and 340 and 8600 km, respectively, for CIS range.
TABLE 1. Result of the Chemical Classification Problema
reference chemicals
classification HPVCs Montreal, Kyoto, Stockholm
inconspicuous (green) 80% 0%
precarious (red) 0% 100%
a As green + yellow + red add up to 100%, green + red can add to
less than 100%, i.e., to 80%.
TABLE 2. Statistics of 2-Fold Cross-Validationa
filter
HPVCs
in
green
HPVCs
in
red
regulated
compds
in green
regulated
compds
in red
Pandora 12.4 ( 1.82 1.0 ( 1.41 0.6 ( 0.55 19.4 ( 1.14
Bioaccumulation 13.4 ( 2.51 1.6 ( 1.14 0.0 ( 0.00 21.2 ( 0.84
a Average ( SD of five different runs in absolute numbers. The
average number of HPVCs was 17.5, while the average number of
regulated (Montreal/Kyoto/Stockholm) compounds was 21.5.
VOL. 39, NO. 3, 2005 / ENVIRONMENTAL SCIENCE & TECHNOLOGY 9 687

6. eters for the respective transformation products are not
available.
Carbaryl and carbofuran are the most widely used
carbamate insecticides. Because of their rapid degradation
in air and water (due to photooxidation, photolysis, hy-
drolysis, and biodegradation) and their low tendency to
bioaccumulate,theirpotentialforpersistenceandlong-range
transport is supposed to be low. Both chemicals pass the
filters, receiving a green score in the Pandora filter and a
yellow one in the Bioaccumulation filter. For an extended
appraisal of carbaryl and carbofuran, their transformation
products carbofuran phenol, 3-hydroxycarbofuran, and
FIGURE 7. Outcome of the Bioaccumulation parameters Koa (octanol-air partition coefficient) and CIG half-life τ for 11 chemicals of special
interest (see Table 3). The dotted straight lines denote the limiting values of 3.27 and 6.89, respectively, for log Koa and 6.31 and 641 days,
respectively, for CIG half-life.
TABLE 3. Filter Series Performance of 11 Chemicals of Special Environmental Interesta
chemicals of special
environmental interest
CIS range
(km)
Pandora CIG
half-life (d)
Pandora
filter log Koa
Bioaccumulation
CIG half-life (d)
Bioaccumulation
filter
medium:
340-8600 km
medium:
9-50 d
medium:
3.27-6.89
medium:
6.3-641 d
R-HCH medium high red high medium red
β-HCH medium high red high medium red
γ-HCH medium high red high medium red
endosulfan medium low green medium low green
carbaryl low low green high low yellow
carbofuran low low green high low yellow
HMDS medium low green medium low green
OMCTS (D4) medium low green medium low green
DMCPS (D5) medium low green medium low green
HBB medium high red high medium red
DBDE medium high red high high red
a The lower and upper limiting values of the amplifying factors are listed in the second row.
TABLE 4. Physicochemical Input Parameters and Calculated Values of the Amplifying Factors for 11 Chemicals of Environmental
Interest
chemicals of special
environmental interest
KHenry
(Pa‚m3/mol) log Kow log Koa kair (1/s) kwater (1/s)
CIS range
(km)
CIG persistence
(d)
R-HCH 1.24E+00 3.80 7.10 1.36E-07 1.08E-07 6209 79.6
β-HCH 7.53E-02 3.78 8.30 1.32E-06 6.32E-08 2169 101.7
γ-HCH 5.21E-01 3.72 7.40 1.84E-07 6.32E-08 5332 113.6
endosulfan 6.59E+00 3.83 6.41 8.00E-5 1.73E-06 428 0.2
carbaryl 3.31E-04 2.36 9.23 5.15E-05 1.89E-06 200 4.3
carbofuran 3.13E-04 2.32 9.22 2.80E-05 2.14E-06 188 3.8
HMDS 4.59E+03 4.20 3.93 1.34E-06 0.00E+00 3321 6.0
OMCTS (D4) 1.19E+04 5.10 4.42 9.80E-07 0.00E+00 3883 8.2
DMCPS (D5) 3.10E+04 5.20 4.10 1.50E-06 0.00E+00 3139 5.4
HBB 2.21E+00 6.07 9.12 1.12E-08 5.35E-07 4577 636.3
DBDE 1.21E-03 5.24 11.55 1.69E-07 2.94E-08 1648 1937.2
688 9 ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 39, NO. 3, 2005

7. 3-ketocarbofuran should be considered. Again, the necessary
input parameters for these compounds are not available.
On the basis of environmental monitoring and general
ecotoxicological considerations, a possible role of silicon
compounds as a general new class of “environmental
chemicals” has been postulated (18). It is then interesting to
test the precautionary filter procedure on some of these
compounds, such as hexamethyldisiloxane (HMDS), octa-
methylcyclotetrasiloxane (OMCTS or D4), and decameth-
ylcyclopentasiloxane (DMCPS or D5), which are man-made
special representatives of the silicones, commonly referred
to as polymethylsiloxanes.
HMDS is a constituent of cosmetic and personal care
products, hydraulic fluids, and serves as a starting material
in the production of other silicone compounds such as D4.
D4isfoundinsoftdrinks,cosmetics,detergents,andpolishes,
whereas D5 is an ingredient of hair care products, antiper-
spirants, cosmetics, and toiletries.
Their environmental behavior and fate is characterized
by moderate volatility, low reactivity in soil and water, and
an estimated high potential for bioaccumulation. Environ-
mental degradation seems to occur only in the air (through
photooxidation by hydroxyl radicals). In water and soil, they
are considered nonreactive with respect to hydrolysis and
biodegradation. They all pass the filters with a green score.
Brominatedcompoundssuchaspolybrominateddiphenyl
ethers (PBDE) are widely used as flame retardants in
consumer products. They have been detected in environ-
mental and human milk samples in industrialized countries,
with increasing concentrations in the past decades. Two of
them are submitted to the two-filter procedure. Hexabro-
mobenzene (HBB) is used as flame retardant in polymers.
It is not expected to be degraded by direct photolysis,
hydrolysis, chemical oxidation, or biological activity. Some
degradation in seawater inocula was reported. Its slow
degradation in air through photooxidation by hydroxy
radicals could be retarded, hexabromobenzene being ex-
pected to exist solely on the particles of the troposphere
(insofar preventing the reaction with hydroxy radicals). Data
on bioaccumulation are controversial, showing potential
bioaccumulation only in long-time studies. It was suggested
that nonaccumulation was due to the size of hexabro-
mobenzene, resulting in lack of membrane permeation.
Hexabromobenzene is retained by both the Pandora and the
Bioaccumulation filters (two red scores).
Decabromodiphenyl ether (DBDE) is used as flame
retardant in textiles, rubbers, and virtually every class of
polymers(ABS,PVC,polyamides,polyesters,polyolefins,etc.)
It degrades in air, water, and soil only in the presence of
sunlight. Hydrolysis and biodegradation have not been
reported. Statements concerning the potential for bioaccu-
mulation are inconsistent (19). It is retained in both the
Pandora filter (red score) and the Bioaccumulation filter (red
score). Debromination of decabromodiphenyl ether leads to
the lower brominated congeners, tetra- to hexabrominated
diphenyls, which readily bioaccumulate. It is unclear what
proportion of the lower brominated congeners in the
environment are breakdown products of DBDE and what
proportion comes from the commercial penta-BDE mixture.
What Has Been Achieved?
First, a kind of scenario technique was used as a basis for
precautionary regulation: Scenarios for uncontrollable harm
were identified as situations to be avoided. The quantitative
representation of scenarios is achieved through filters. Each
filter is defined via a small set of relevant assessment
parameters.
Then, a filter series approach was presented, which is an
alternative to the familiar risk-benefit valuations in situations
where risks (i.e., probability times magnitude of adverse
effects) cannot be specified because the spectrum of the
adverse effects is largely unknown. As a formal scheme the
filter series procedure is independent of particular hazards.
Next, in a case study dealing with special features of large-
scale hazards of organic chemicals, two types of two-
parameter filters have been constructed and suitably cali-
brated. The sequence of two filters was shown to reproduce
in a shortcut essential results of a long and cumbersome
historical development. (A short preview on precautionary
filters and Pandora filtering was provided by Mu¨ller-Herold;
20.) In the given context of large-scale threats, the respective
assessment parameters play the role of amplifying factors.
The interplay of amplifying factors in the diverse threat
scenarios is then taken into account using two-parameter
filters. Two-parameter filters compensate for the one-
sidedness of limiting values for single assessment param-
eters: In the Pandora scenario, the interplay of the two
parameters prevents concrete, bitumen, and plastics from
being eliminated on the basis of persistence (as their mobility
is too low), and in the Bioaccumulation scenario they keep
the silicones from being eliminated on the basis of high Kow
values (as their lifetime is too short).
Theusualpracticeofdefininglimitingvaluesforindividual
parameters through a body of experts was then comple-
mented by a kind of self-calibration of filters on the basis of
reference chemicals with broadly accepted, unequivocal
international regulatory status. These sets of chemicals are
comparably small and cannot be easily extended without
loss of regulatory status. Calibration and validation have to
properly deal with this situation. However, if industry finds
that thresholds thus obtained are too low or NGOs think
they are too high, calibration can be altered by political
decision makers (without questioning the precautionary pre-
screening procedure as a whole.) Such new calibrations,
though, would not be based on the Montreal/Kyoto/
Stockholm Protocols or the U.S. HPVCs, and a new consensus
would have to be found at an international level (due to the
WTO).
In cases of several scientifically equivalent methods, we
consistently chose the one that was likely to be more suitable
for public debate, as citizen participation is one of the
declared objectives of the EU. Accordingly, closed analytical
formulas were preferred to numerical computer calculations
whenever possible. For this purpose we developed concepts
such as CIG range, CIS lifetime, CCP cold condensation
potentials, secondary ranges, etc. The references cited and
the Supporting Information allow the interested reader to
get an idea of these concepts. The mathematics for their
derivation can be found in more technical papers in
Environmental Science and Technology and Ecological Mod-
elling, respectively. Finally, a first look on a group of
nonreferential chemicals of special environmental interest
links up to the discussion of nonreferential compounds.
To conclude, a procedure is presented that fits into the
general architecture of the PrecauPri model, building on the
three pillars of screening, appraisal, and management (21).
The model was developed in a cooperation of social scientists
specialized in risk and uncertainty issues, natural scientists,
and a legal scholar with special expertise in risk regulation.
It honors and carries forward the EU’s philosophy of
precautionary policies and good governance and may be
used as a template for precautionary risk regulation within
and beyond the EU context.
Outlook
Although the approach to precautionary pre-screening
presented here was developed as an answer to the needs of
regulative authorities, a far more extended application is
conceivable: Ideally, a chemist designing a new compound
on paper could directly “send it through the filters”. At this
VOL. 39, NO. 3, 2005 / ENVIRONMENTAL SCIENCE & TECHNOLOGY 9 689

8. early stage, of course, the measurable input parameters have
to be replaced by theoretical or estimated values. In
combination with a suitable software solution, a first
preliminary precautionary pre-screening could be under-
taken directly after the molecule has first appeared on a
chemist’s drawing table. In this way, precaution could come
into playsprior to the synthesis of one single molecule of a
precarioussubstance.Thiswouldbepreventionatthesource.
Note Added in Proof
The authors want to draw the readers’ attention to a recently
published paper by P. Sandin et al. (27), which opens a
different perspective to precautionary regulation of chemi-
cals.
Acknowledgments
This work was funded under Grant BBW-NR. 00.0487 of the
Swiss Federal Office for Education and Science. The authors
are indebted to Susanna Bucher (Zurich) for technical
support, Martin Scheringer (Zurich) for valuable discussions,
andToniJarimo(Helsinki)forhiscontributionstocalibration
and validation.
Appendix
Spatial Range and Persistence. A closed analytical formula
for characteristic isotropic spatial (CIS) range F has been
derived by Mu¨ller-Herold and Nickel (22):
with
For characteristic isotropic global (CIG) half-lives (τ), the
formula
was used. The symbols denote the relevant unit world
parameters and the substance-related quantities.
Unit World Parameters. r ) 6381 km is the radius of the
earth, which entails that πr ) 20 037 km is the maximally
possible spatial range. The calibration of the unit world’s
relative compartment volumes (Vi) and eddy diffusion
constants (Di) are taken as
Substance-Related Input Quantities. ka, kw, and ks are
the degradation rate constants for air, water, and soil,
respectively. If Kij ) cieq/cjeq denotes the equilibrium partition
between compartments i and j, then Kwa and Ksa are the
water-air and soil-air partition coefficients. Kwa and Ksa are
obtained from a chemical’s Henry’s law constant KH (in Pa
m3
mol-1
) and octanol-water partition coefficient Kow by
FollowingKarickhoff(23),thefractionfoc oforganiccarbon
in soil is set to 0.02. The factor 0.41 converts the octanol-
water partition coefficient into the organic carbon-water
partition coefficient Koc; Ksw is the soil-water partition
coefficient. The Henry’s law constants are taken for distilled
water. Seawater corrections, usually giving an increase of
20-40%, are neglected. As this applies to all substances, it
enters the filter calibration and does not lead to arbitrary
distortions.
For legal considerations, degradation constants (ks) in
soilaresettozero.Assoilisahighlyinhomogeneousmedium,
degradation constants in soil are not justiciable (i.e., liable
to be tried in a court of justice). Their inclusion would
undermine legal certainty. This choice of ks leads to slightly
increased CIS ranges and CIG half-lives. In the context of
precautionary pre-screening, it always leads to results on
the safe side, accordingly. As the assumption applies to all
substances,itentersthefiltercalibration.Testingitsinfluence
on the output, results have shown that in most cases it has
novisibleeffect.(Theinhomogeneityargumentisnotapplied
to the soil-water partition coefficient as the Karickhoff
procedure seems to be generally accepted. Soil, accordingly,
enters the scenario as a lipophilic storage medium.)
Comments: CIS Ranges. The CIS ranges are based on a
three compartment isotropic global unit-world scenario
involving the main global compartments: the troposphere,
the surface water of the oceans, and the upper layer of the
soil. The concept of CIS ranges was first introduced by one
of the present authors (U.M.H.) together with M. Scheringer
and M. Berg 10 years ago (24) and is preferred to simpler
methods based on single media lifetimes, which can give
wrong results. (For details, see Section 8.3 of the Supporting
Information.)
Comments: CIG Half-Lives. The τ formula with k∞ has
been used for a long time in environmental and other multi-
compartment models. It is a direct consequence of the so-
called instant equilibrium assumption presuming rapid
equilibration of the chemical potentials of a substance in the
respective compartments. A widely known application of the
instant equilibrium assumption is gas chromatography. It
has been demonstrated by Mu¨ller-Herold (25) and Mu¨ller-
Herold et al. (26) that half-lives based on the instant
equilibrium assumption (i) are highly precise in the case of
rapid exchange between the compartments; and (ii) in all
cases they give an upper value to real half-lives calculated
withouttheinstantequilibriumassumptioninmoreextended
models with corresponding input parameters. If used in
precautionarypre-screening,theformulaalwaysgivesresults
on the safe side, accordingly.
The CIG half-lives as used in the present setup are based
on a three-compartment isotropic global unit-world scenario
involving the main global compartments: the troposphere,
the surface water of the oceans, and the upper layer of the
soil.
Supporting Information Available
Physicochemical input parameters, calculated values of the
amplifying factors, and filtering results of the reference
chemicals; details of the first Jarimo procedure for filter
calibration and a digression on uncertainty aspects of the
present approach; a sketch on complementing filters (Trans-
formation Pandora, Cold Condensation) and on a three-filter
sequence; an outlook on REACH, the three-level testing and
regulatory system presently discussed in the EU; an account
of several discussions with reviewers of this paper. This
material is available free of charge via the Internet at http://
pubs.acs.org.
F ) e D/k tanh(πr k/D) exp{π/2 - 2 arctan[eπr k/D
]
sinh (πr k/D) }
D/k )
DaVa + DwKwaVw + DsKsaVs
kaVa + kwKwaVw + ksKsaVs
τ )
ln 2
k∞
, k∞ )
def kaVa + kwKwaVw + ksKsaVs
Va + KwaVw + KsaVs
compartment Di (km2 s-1) Vi (m3)
water (w) 0.01 233
air (a) 2 200 000
soil (s) 0 1
Kwa ) RT/KH
Ksw ) focKoc ) 0.02 × 0.41Kow
Ksa ) KswKwa
690 9 ENVIRONMENTAL SCIENCE & TECHNOLOGY / VOL. 39, NO. 3, 2005

9. Literature Cited
(1) Commission of the European Communities. Communication
from the Commission on the Precautionary Principle; COM 2000
No. 1; Brussels, February 2000.
(2) Sandin, P. Dimensions of the precautionary principle. Hum.
Ecol. Risk Assess. 1999, 5, 889-907.
(3) Ravetz, J. R. The sin of sciencesignorance of ignorance.
Knowledge 1993, 15, 157-165.
(4) Weber, D. Das Ende des Fischotters in der Schweiz; Schriftenreihe
Umwelt Nr. 128, Bundesamt fu¨r Umwelt, Wald und Landschaft
(BUWAL), 1990. (The End of the Otter in Switzerland; Swiss
Federal Environmental Protection Agency Series No. 128, 1990).
FromtheAbstract: “ThePCB-(polychlorinatedbiphenyl-)levels
in fish from Switzerland are generally several times higher than
those which would allow reproduction of the otter. Switzerland
has to be considered as a country where viable otter populations
cannot exist now and in the foreseeable future because PCB
levels in fish are much too high.”
(5) Mu¨ller-Herold, U. Measures of endangerment. Geneva Pap. Risk
Ins. 1996, 21, 383-392.
(6) In the EU the current practice is codified in the European
Communities 1997 Technical Guidance Document in support
of Commission Directive 93/67/EEC on risk assessment for new
notified substances and in the Commission Regulation (EC)
No. 1488/94 on risk assessment for existing substances,
Luxembourg Office for Official Publications of the European
Communities.
(7) Quartier, R.; Mu¨ller-Herold, U. On secondary spatial ranges of
transformationproductsintheenvironment.Ecol.Modell.2000,
135, 187-198.
(8) Fenner, K.; Scheringer, M.; Hungerbu¨hler, K. Persistence of
parent compounds and transformation products in a level IV
multimedia model. Environ. Sci. Technol. 2000, 34, 3809-3817.
(9) Klinke, A.; Renn, O. A new approach to risk evaluation and
mangement: risk-based,precaution-basedanddiscourse-based
management. Risk Anal. 2002, 22, 1071-1094.
(10) Scheringer, M.; Berg, M. Spatial and temporal range as measures
of environmental threat. Fresenius Environ. Bull. 1994, 3, 493-
498.
(11) Scheringer, M. Persistence and Spatial Range of Environmental
Chemicals: New Ethical and Scientific Concepts for Risk Assess-
ment; Wiley-VCH: Weinheim, 2002.
(12) Connell, D. W. Bioaccumulation of Xenobiotic Compounds; CRC
Press: Boca Raton, FL, 1990.
(13) American Chemical Society. Chem. Eng. News 1996, June 24;
http://pubs.acs.org/hotartcl/cenear/960624/prod.html.
(14) Jarimo, T. Two Algorithms for the Calibration of Precautionary
Filters; unpublished (available as pdf at http://e-collection.
ethbib.ethz.ch/cgi-bin/show.pl?type ) bericht&nr ) 247).
(15) Schucht, O. Partial order theory in the assessment of environ-
mental chemicals: formal aspects of a precautionary pre-
selection procedure. Ph.D. Thesis, ETH, Zurich, 2004.
(16) Efron, B.; Tibshirani, R. An Introduction to the Bootstrap;
Chapman and Hall: New York, 1993.
(17) Calamari, D.; Bacci, E.; Focardi, S.; Gaggi, C.; Morosini, M.; Vighi,
M. Role of plant biomass in the global environmental partition-
ing of chlorinated hydrocarbons. Environ. Sci. Technol. 1991,
25, 1489-1495.
(18) Reller, A.; Braungart, M.; Soth, J.; von Uexku¨ll, O. Siliconeseine
vollsynthetischeMaterialklassemachtGeschichte(n).GAIA2000,
9, 13-24.
(19) National Library of Medecine, National Institutes of Health.
Hazardous Substances Data Bank; http://toxnet.nlm.nih.gov/
cgi-bin/sis/htmlgen?HSDB; enter search term decabromobi-
phenyl ether.
(20) Mu¨ller-Herold, U. Quantitative Vorsorgebewertung neuer Chemi-
kalienimHinblickaufglobaleGefa¨hrdungsszenarios.GAIA2002,
11, 46-47.
(21) Renn, O.; Dreyer, M.; Klinke, A.; Losert, C.; Stirling, A.; van
Zwanenberg, P.; Mu¨ller-Herold, U.; Morosini, M.; Fisher, E. The
Application of the Precautionary Principle in the European
Union; Final document of the EU Project Regulatory Strategies
and Research Needs to Compose and Specify a European Policy
on the Application of the Precautionary Principle; http://
www.sussex.ac.uk/spru/environment/precaupripdfs.html.
(22) Mu¨ller-Herold, U.; Nickel, G. A closed analytical formula for the
characteristicspatialrangeofpersistentorganicpollutants. Ecol.
Modell. 2000, 126, 191-200.
(23) Karickhoff, S. W. Semi-empirical estimation of sorption of
hydrophobic pollutants on natural sediments and soils. Chemo-
sphere 1981, 10, 833-846.
(24) Scheringer, M.; Berg, M.; Mu¨ller-Herold, U. Jenseits der
Schadenfrage: Umweltschutz durch Gefa¨hrdungsbegrenzung.
In Was ist ein Schaden? Zur normativen Dimension des
Risikobegriffes; Berg, M., et al., Eds.; VdF: Zu¨rich, 1994; pp 115-
146.
(25) Mu¨ller-Herold, U. A simple general limiting law for the overall
decay of organic compounds with global pollution potential.
Environ. Sci. Technol. 1996, 30, 586-591.
(26) Mu¨ller-Herold, U.; Caderas, D.; Funck, P. Validity of global
lifetime estimates by a simple general limiting law for the decay
of organic compounds with long-range pollution potential.
(27) Sandin, P.; et al. Precautionary defaults-a new strategy for
chemical risk management. Hum. Ecol. Risk Assess. 2004, 10,
1-18. Environ. Sci. Technol. 1997, 31, 3511-3515.
Received for review May 21, 2004. Revised manuscript re-
ceived September 24, 2004. Accepted October 13, 2004.
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