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http://slidepdf.com/reader/full/1072325 1/16

Comparison of two screening level risk assessment

approaches for six disinfectants and pharmaceuticals

Annemarie P. van Wezel *, Tjalling Jager

National Institute for Public Health and the Environment, P.O. Box 1, 3720 Bilthoven, BA, Netherlands

Received 11 December 2000; received in revised form 7 January 2001; accepted 24 January 2001

Abstract

For three examples of both groups (the disinfectants biphenylol, 4-chloro-m-cresol and triclosan and the pharma-

ceuticals ivermectin, ibuprofen and oxytetracycline) a relative initial risk assessment (RIRA) was performed assuming a

standard emission of 1 kg/d to the most relevant environmental compartment. In addition the hazard of the compounds

was evaluated based upon their persistence, toxicity and bioaccumulative properties (PTB). Both estimated and

measured parameters were used for this purpose. In addition to an analysis of the risks of the pharmaceuticals and

disinfectants per se, the capacity to discern between the intrinsic risk of different compounds is evaluated for both

criteria used. It is concluded that the RIRA has a higher discriminative value and yields more information compared to

the PTB-criterion. Ó 2002 Elsevier Science Ltd. All rights reserved.

Keywords: Biphenylol; 4-Chloro-m-cresol; Triclosan; Ivermectin; Ibuprofen; Oxytetracycline

1. Introduction

For a relatively limited number of compounds,

information on toxicological and physical–chemical

properties, emissions or environmental concentrations is

collected or risk assessments are made. Less than 600

substances are under the attention of various interna-

tional organisations, for these compounds this kind of

information is systematically collected (EU, OECD,

WHO-IPCS, UN-EP, UN-ECE, OSPARCOM andICPR, see for an overview van Wezel, 1999). Much more

chemicals occur in our environment, numbers are esti-

mated to be higher than 100 000.

Are there other substances than the aforementioned

600, which need more policy attention? This can be

evaluated by using priority setting schemes (Halfon et al.,

1996; Eisenberg and McKone, 1998; Blok et al., 1999;

Hansen et al., 1999), however the chosen method is

critical for the ranking obtained (Hertwich et al., 1998).

Another approach is to study measured concentrations

in the environment, information from scientific litera-

ture or information on emission of substances. For the

Netherlands, substances were selected that possibly de-

serve more policy action using the aforementioned

methods except priority setting systems (van Wezel and

Kalf, 2000). As an example, compounds that are mea-sured in significant amounts in environmental matrices

are given in Table 1. Major compound classes that are in

focus in recent scientific literature are pharmaceutical

substances (Warman and Thomas, 1981; Henschel et al.,

1997; Halling-Sørensen et al., 1998; Al-Ahmad et al.,

1999; Buser et al., 1999; Jørgensen and Halling-Søren-

sen, 2000; Zuccato et al., 2000), disinfectants (Hektoen

et al., 1995; Ternes et al., 1998), (anti-) estrogenic com-

pounds (Gillesby and Zacharewski, 1998; Janssen et al.,

1998; Tyler et al., 1998), biotransformation products of

pesticides (Belfroid et al., 1998), fluorescent whitening

agents (Van de Plassche et al., 1999), non-classic flame

Chemosphere 47 (2002) 1113–1128

www.elsevier.com/locate/chemosphere

* Corresponding author. Tel.: +31-30-2744401; fax: +31-30-

2742971.

E-mail address: [email protected] (A.P. van Wezel).

0045-6535/02/$ - see front matter Ó 2002 Elsevier Science Ltd. All rights reserved.

PII: S0 0 4 5 -6 5 3 5 (0 2 )0 0 0 4 8 -6

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retardants (WHO, 1997, 2000) and aromatic substances

(Rimkus and Wolf, 1995).

For two groups, i.e. pharmaceutical compounds anddisinfectants, compounds were selected to evaluate if

there is indeed reason for concern. This was based on

the PTB-profile of the compounds, or based on relative

initial risk assessment (RIRA), both explained below.

The PTB-profile is based on the so-called intrinsic

chemical properties persistence, toxicity and bioaccu-

mulative potential (Sijm et al., 1999). For each of these

three properties various classes are defined, related to a

distinction in environmental risks. The cut-off levels

between the classes are distinct. The three properties are

taken together and integrated, and substances are de-

fined in terms of having ‘high priority’, ‘medium prior-

ity’ or ‘low priority’.

For RIRA, the same type of data is needed as for

the PTB-profile. Based on an assumed standard rate of

emission, the corresponding environmental concentra-

tion in the various compartments is calculated (water,

sediment, soil, bioaccumulating organisms). There-

fore — estimated — properties related to environmental

fate are used, such as the vapor pressure, water solu-

bility, octanol/water partition coefficient and the organic

matter/water partition coefficient. The modeled envi-

ronmental concentration is compared to concentrations

yielding adverse effects. This procedure is termed RIRA,

as no information on actual use or emission of thechemical is needed in contrary to an initial risk assess-

ment. Obtaining information on uses or emission is

generally labour-intensive. The RIRA approach is com-

parable to the use of USES in LCA to calculate ‘‘toxicity

potentials’’ (Huijbregts et al., 2000).

In addition to an analysis of the risks of the phar-

maceuticals and disinfectants per se, the capacity to

discern between the intrinsic risk of different compounds

is evaluated for both criteria used, i.e. PTB-profile and

RIRA. The work is done as part of the development of

Dutch policy towards substances, in which one of the

ideas is to classify substances in terms of ‘very high

concern’, ‘high concern’, ‘concern’ and ‘expected no

concern’.

2. Methods

2.1. Selection of compounds

Compounds were selected that were relatively data-

rich. A second criterion was that there is some informa-

tion on environmental concentrations of the compounds

chosen. Based on these criteria, the disinfectants biphe-

nylol (CAS-no. 90-43-7), 4-chloro-m-cresol (CAS-no.

59-50-7) and triclosan (CAS-no. 3380-34-5) and the

pharmaceuticals ivermectin (CAS-no. 70288-86-7), ibu-

profen (CAS-no. 15687-27-1) and oxytetracycline (CAS-

no. 79-57-2) were chosen.

2.2. Data sources

Search for data on the selected chemicals was not

exhaustive. Sources of data were

• http://www.chemfinder.com

• http://www.citi.or.jp

• Mackay et al. (1999).

• Abstracts of dossiers provided by industry for au-

thorisation procedures on ivermectin, biphenyloland oxytetracyclin.

• Electronic search using the databases TOXLINE

PLUS 1985–1999, DOSE, Current Contents 1996–

1999, CHEMBANK and MEDLINE 1966–1999,

on chemical name/CAS-no. and ecotoxÃ, environÃ and

concentratÃ, carcinogenÃ or mutagenÃ or teratogenÃ

or oestroÃ or estroÃ or hormonÃ or endocrinÃ. Except

for reviews, original articles were not retrieved. The

information used was derived from abstracts and

was checked until April 2000.

• US-EPA databases AQUIRE and TERRETOX,

http://www.epa.gov/ecotox.

Table 1

Compounds measured in significant amounts in environmental matrices, that are not subject of (inter)national risk assessments

Environmental

matrix

Non-priority compounds encountered Reference

Biota (mussel,

eel)

Octachlorostyrene Hendriks et al.

(1998)

Effluents from

sewage treatment

plants

2,6-Diisobutylphenol, HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethyl-cyclopenta-

gamma-2-benzopyran), limonene, AHTN (6-acetyl-1,1,2,4,4,7-hexamethyltetraline)

Van Loon et al.

(1997)

Surface waters HHCB, AHTN Verbruggen et al.

(1999)

Effluents from

sewage treatment

plants

Galaxolide, tonalide, traseolide, celestolide, phantolide, vertofix, triclosan, triclosanm-

ethyl, chlopyrifos, butylated hydroxytoluene

Leonards et al.

(unpublished

results)

1114 A.P. van Wezel, T. Jager / Chemosphere 47 (2002) 1113–1128

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• Missing properties were estimated with EPI ¼

EPIWIN v2.30 (esc.syrres.com). The estimation soft-

ware contains different modules for estimating prop-

erties related to environmental fate parameters, such

as the octanol/water partition coefficient, biodegrada-

tion, atmospheric half-life, bioconcentration factor,

etc. In principle, reliable measured data were pre-

ferred over estimated data.

2.3. Calculations

2.3.1. PTB-criterion

The chemical properties are summarised according

to the PTB-profile of Sijm et al. (1999). Cut-off val-

ues between classes for an intrinsic property are used

as given in Table 2. The most hazardous class is ‘‘3’’,

the less hazardous ‘‘2’’ and ‘‘1’’. Compounds are defined

as having ‘‘high priority’’ when all criteria fall in class

3. If more than one criterion falls in class 3 the com-

pound has ‘‘medium priority’’. If some criteria fall inclass 1 the compound is concerned as having ‘‘low pri-

ority’’.

2.3.2. Relative initial risk assessment

Information on P, T, and B was also used to make a

‘‘relative’’ initial risk assessment, performed with EU-

SES (Vermeire et al., 1997) based on the most likely

data. The regional scale was chosen, combined with a

standard emission of 1 kg/d to the most relevant envi-

ronmental compartment based on the expected use

pattern. Based on this assumed standard rate of emis-

sion, the corresponding environmental concentration inthe various environmental compartments is calculated.

For this end — estimated — properties related to envi-

ronmental fate are used. The use of the regional scale

includes that the environmental concentrations will be

spatially averaged over the entire region. Experimental

data are used when possible. If no experimental toxicity

data were available for soil or sediment, the risk was

characterised by assuming equilibrium partitioning.

When possible, information on the actually measured

environmental concentration of a chemical was used to

estimate the actual risk. The actual risk can also be

obtained by multiplying the relative risk levels by the

actual emitted quantities; the EUSES fate models are

linear with respect to emission quantity.

3. Results

3.1. Disinfectants

3.1.1. Biphenylol

Biphenylol is used for its antimicrobial action in a

range of industrial, agricultural and household applica-

tions. It is used as disinfectant, for surface treatment, as

fungicide, preservative and as intermediate for dyes.

Following Verhaar et al. (1992) the mode of action is

polar narcosis.

The chemical is relatively data-rich (Appendix A).

Except for vapour pressure, the physical–chemical

properties are accurately estimated by EPI. Quantitative

data on the use or emission in the Netherlands are notreadily available. The chemical is assumed to be dis-

charged via sewage treatment plants (STPs). In view of

the conflicting K oc estimates (Appendix A), two scenar-

ios were run in the calculations with K oc set to 500 and

10 300 l/kg. The chronic NOAEL for mammals reported

is >500 mg/kg/d. The ADI for this chemical is 0.02 mg/

kg/d. Assuming an assessment factor of 100, the original

NOAEL was 2 mg/kg/d, this value was used in the

RIRA.

The PTB profile of this chemical results in a classi-

fication of low priority (Table 3). Chemical partitioning,

according to Mackay level I, is mainly to soil.

The relative risks for water, soil and sediment are

in the same order of magnitude, assuming a high K oc

(Table 4). If a low K oc is assumed the relative risk of soil

is somewhat lower compared to sediment and water

(Table 4). Risks to predators are low, despite the use of a

strict NOAEL of 2 mg/kg/d.

Mensink (1999) estimated the use in the Netherlands

on 10 ton/yr. Assuming all is released to wastewater, the

resulting PEC/PNEC ratios are well below 1. The PNEC

is quite conservative due to a lack of chronic toxicity

data. However, the chemical is suspected as a xeno-

estrogen so scrutiny is necessary. Measured concentra-

tions in Eijsden (Leonards et al., unpublished results) area factor 10 higher than regionally estimated concentra-

tions. The measured concentrations indicate a tonnage

between 160 and 240 ton/yr, but again indicate a low

risk although the safety margin with the PNEC is only a

factor of 10. Data from Germany indicate a higher risk

(Ternes et al., 1998). For the river Ruhr the PEC/PNEC

ratio exceeds one, for the wastewater from hospitals the

PEC/PNEC ratio even exceeds 100.

3.1.2. 4-Chloro-m-cresol

4-Chloro-m-cresol is used as disinfectant or antiseptic

and as preservative. It enters the environment mainly via

Table 2

Chosen cut-off values of the properties P, T, and B

Class Persistence Toxicity

(mg/l)

Bioaccumula-

tion

1 DT506week LC50P 1 Log K ow64

2 DT50 > week LC50 < 1 Log K ow > 4

3 DT50 > month LC50 < 0:1 Log K ow > 5

A.P. van Wezel, T. Jager / Chemosphere 47 (2002) 1113–1128 1115

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STPs. Following Verhaar et al. (1992), the mode of ac-

tion of the chemical is polar narcosis. 4-Chloro- m-cresol

is data-rich (Appendix A).We did not dispose of quantitative data on the use of

4-chloro-m-cresol in the Netherlands. To perform the

calculations, the BCF was set to maximum of the ex-

perimental range and ready biodegradability was as-

sumed, as both the estimation and the HSDB data

indicated this. In addition, a calculation assuming in-

herent degradability was performed.

PNEC for the aquatic environment is based on the

reported NOECs, the reported extremely low LC50 of

10 lg/l is considered an outlier. For the terrestrial en-

vironment, equilibrium partitioning is applied as well asthe reported EC50 for lettuce.

The PTB profile of this chemical indicates little rea-

son for concern (Table 3). Mackay level I predicts a

major part of the chemical in soil (93%) whereas the

level III calculation of EUSES predicts 59% in soil and

25% in water. The relative risks (Table 4) are low com-

pared to the other evaluated chemicals.

Only few measured data are available for this com-

pound. Reported monitoring data (HSDB database)

from the UK for ‘‘final effluent’’ of 73 ng/l would imply

a minimal risk (safety margin > 1000). The same data-

base reports a range for several raw and treated waste-waters, which is extremely broad (0:01Â 105

lg/l) and

the higher levels yield a serious risk. Details about these

figures are however lacking.

3.1.3. Triclosan

Triclosan is a non-ionic, broad-spectrum anti-

microbial agent and is incorporated in variety of

personal care products such as deodorants, soaps,

toothpaste, shower gels. It probably mainly enters the

environment via the effluent of STPs. The mode of ac-

tion of triclosan is classified as either a reactive chemical

or a non-polar narcotic chemical (following Verhaaret al., 1992).

The experimental dataset (Appendix A) is consid-

ered as limited for a chemical with such a wide-

spread application. The chemical is expected to partition

Table 4

Risk characterisation of the studied compounds after a RIRA with an hypothetical emission of 1 kg/d

Chemical Scenario Water Soil Sediment Fish-eater Worm-eater

Disinfectants

Biphenylol High K oc 1:2Â 10À4 3:7Â 10À4 2:1Â 10À4 2:1Â 10À5 6:5Â 10À5

Low K oc 1:7Â 10À4 7:9Â 10À5 1:7Â 10À4 3:0Â 10À5 1:4Â 10À5

4-Chloro-m-cresol Inherently biodegradable 4:5Â 10À5 1:2Â 10À4 5:9Â 10À5 5:4Â 10À6 2:8Â 10À6

Ready biodegradable 4:4Â 10À6 1:1Â 10À5 4:4Â 10À6 5:2Â 10À7 2:6Â 10À7

Triclosan Inherently biodegradable 9:0Â 10À3 8:5Â 10À3 1:7Â 10À2 1:1Â 10À3 4:9Â 10À2


Pharmaceuticals

Ivermectin Inherently biodegradable 0.27 5.5 1:5Â 10À2 3:2Â 10À4 7:3Â 10À3

Ready biodegradable 5:7Â 10À3 0.28 3Â 10À4 6:9Â 10À6 3:7Â 10À4

Ibuprofen Inherently biodegradable 1:7Â 10À5 2:0Â 10À6 2:2Â 10À5 1:7Â 10À4 2:3Â 10À3


Oxytetracycline Inherently biodegradable 4:6Â 10À3 3:2Â 10À4 3:2Â 10À3 8:1Â 10À7 6:9Â 10À9


Figures in bold represent the environmental compartment most at risk.

Table 3

PTB-criterion for the studied compounds

P T B ‘‘PTB-pri-

oritary’’

Disinfectants

Biphenylol

Only estimates 1 1 1 Low

Best guess 1 2 1 Low

4-Chloro-m-cresol



Triclosan

Only estimates 1 1/3 2 Low


Pharmaceuticals

Ivermectin

Only estimates 2 3 2 Medium

Best guess 1/2 3 1 Low

Ibuprofen

All estimates 1 1/3 1 Low

Best guess 1/2 1 1 Low

Oxytetracycline




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mainly to soil (Mackay level I). Despite, data on soil

toxicity, sorption or degradation in soil are lacking. Data

on the total use of triclosan in NL were not available.

In view of the limited data for degradation two

scenarios were run in the RIRA, i.e. readily and inher-

ent biodegradability. The BCF was set to 50 l/kg. For

chronic toxicity for mammals and birds a default valueof 1 mg/kg/d was used.

The PTB profile of triclosan points to a low priority

of the chemical (Table 3).

The RIRA (Table 4) indicates the highest relative risk

for the worm-eating predators (possibly because of the

default NOAEL applied), followed by the sediment

system.

The chemical was identified in a survey with

semi-permeable membrane devices (SPMDs) in surface

waters of the Netherlands (Leonards, unpublished data).

SPMDs are filled with a fat-like substance like triolein

and can be used to perform time-integrated measure-ments of compounds with a low water solubility (Booij

et al., 1998). Measured concentrations were 540 and

150 ng/g triolein in Eijsden (Meuse) and Schaar van

Ouden Doel (Scheldt), respectively. From these values

water concentrations can be estimated (Booij et al.,

1998) of 7.7 and 2.1 ng/l. The risk associated with

this water concentration is low but the safety margin

with the PNEC is a factor of 30 only. The situation can

be more critical locally, e.g. in the vicinity of a STP

outlet.

3.2. Pharmaceuticals

3.2.1. Ivermectin

Ivermectin is a broad-spectrum anti-parasitic drug.

Treated animals excrete the mainly unchanged com-

pound via the faeces. Ivermectin is also used in hu-

mans for treatment of endoparasites. Ivermectin acts on

nematodes and arthropods by blocking GABA-medi-

ated transmission of nerve signals (Wand and Pong,

1982). Ivermectin is classified as a reactive chemical

(Verhaar et al., 1992).

Data for ivermectin are given in Appendix A. The

available terrestrial toxicity data indicate low terrestrialtoxicity, however data on the terrestrial target organisms

(arthropods and nematodes) are lacking. Given the ex-

tremely high aquatic toxicity for daphnids, the lack of

toxicity data for terrestrial target organisms is worri-

some.

The chemical is expected to partition mainly in soil

(Mackay level I). Quantitative data on the use of iver-

mectin in the Netherlands are not readily available, and

also data on measured concentrations in soil or surface

waters are lacking.

To perform calculations, the K oc was set to 8000 l/kg

and the BCF was set to 60 l/kg. As reported degradation

rates vary, two scenarios were run, i.e. inherently de-

gradable and a DT50 in soil of 200 days, the second

scenario is readily degradable and a DT50 in soil of 10

days.

The PTB profile (Table 3) stresses the high toxicity of

this chemical. The persistence is not very high and the

potential for bioaccumulation is small, with as a result amedium or low priority. The risk as characterised using

RIRA is given in Table 4. The terrestrial risk based on

soil toxicity data, is low relative to the risk for the water

compartment. Assuming equilibrium partitioning, the

resulting terrestrial risk is much higher. In view of the

lack of terrestrial arthropod data, the EP method was

chosen here. The chemical may exceed a PEC/PNEC

ratio of one already at a very low tonnage. Even if

readily biodegradability is assumed, an emission of 1.3

ton/yr for soil or 64 ton/yr for water leads to an ex-

ceeding of the PEC/PNEC ratio and thereby to risks for

ecosystem health. As ivermectin has a direct route of entry into the soil compartment, a smaller area of the

total system can be considered which leads locally to a

higher concentration. The use of ivermectin may very

well affect dung-dwelling and dung-feeding insects di-

rectly at the prescribed dose (cf. Lumaret et al., 1993;

Halling-Sørensen et al., 1998; Dadour et al., 1999).

3.2.2. Ibuprofen

Ibuprofen is a widely used in humans as painkiller

and anti-inflammatory drug. The compound is rapidly

excreted in urine, mainly as metabolites (Busson, 1986).

The main route of entry to the environment is via the

wastewater. Following Verhaar et al. (1992) the chemi-

cal might either be classified as a reactive chemical or as

a polar narcotic.

The dataset for ibuprofen (Appendix A) is reason-

ably complete. The estimated data should be treated

with care, as the chemical will be dissociated at environ-

mental pH values. Dissociation probably also explains

the difference between the estimated and experimental

water solubility.

For the EUSES calculations, the properties of the

parent compound — not the metabolites — were used to

model the distribution. The chemical was treated asinherently degradable or ready biodegradable as an

alternative. The chemical will be ionised, therefore

the vapour pressure was set low (1 Â 10À6 Pa). Chronic

mammalian toxicity data lack, a default of 1 mg/kg/d

was used. The maximum dose for treating a 70 kg hu-

man would amount to 34 mg/kg/d, although negative

side effects are observed with this chemical at the rec-

ommended dose.

The PTB profile (Table 3) gives little reason for

concern.

Mackay level I predicts a major fraction of the

chemical in soil (94%). In the EUSES calculations


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according to Mackay level III, this is less (55–57%) with

36% in the water compartment. The EUSES calculation

assumes that all STP sludges are applied as fertilizer.

The relative risk (Table 4) is highest for the preda-

tors, owing to the low default NOAEL used.

Recent tonnage data for Denmark are available of 33

ton/yr (Halling-Sørensen et al., 1998, Stuer-Lauridsen

et al., 2000). Assuming the same consumption per capita

in the Netherlands, the Dutch consumption is estimated

100 ton/yr. Based on this, the PEC/PNEC ratios for

water, sediment and soil remain well below one (safety

margins with the PNEC of 500 or more).

Concentrations measured in Rhine and other fresh

surface waters in Germany and Switzerland are in the

ng/l range with a maximum of 140 ng/l, for STP effluentsvalues of 3.4 lg/l are reported (Halling-Sørensen et al.,

1998; Ternes et al., 1998; Buser et al., 1999; Stuer-Lau-

ridsen et al., 2000). The measured data for the Rhine are

in good agreement with the estimated concentrations

assuming ready biodegradability. The PEC/PNEC ratios

on the basis of the measured data are well below one,

also for the maximum reported effluent concentrations

(see Table 5).

3.2.3. Oxytetracycline

Oxytetracycline is a well-known antibacterial agent

(fungicide/bactericide/algicide), produced by a fungus. Ithas very diverse applications: e.g. on fruit trees, as ma-

rine anti-fouling paint, as veterinary and human phar-

maceutical.

The route of entry in the environment varies with the

application. The chemical cannot be classified following

the scheme of Verhaar et al. (1992).

The dataset (Appendix A) is limited with respect to

physico-chemical properties. Given the structure and

different possible charges of the molecule, the estimates

of vapour pressure and water solubility are question-

able.

For the calculations, DT50 in water is set on 15 days

and DT50 in soil is set equal to sediment. Additionally,

a calculation assuming inherent biodegradability is

performed. A NOAEL of 100 mg/kg/d is applied. Only

emission via STP is considered. To examine the impor-

tance of the doubtful value for water solubility an ad-

ditional calculation is performed with solubility on 1 mg/

l, giving identical results.

The PTB profile of this chemical (Table 3) shows a

low priority for this chemical. Note the difference in

score for toxicity using either experimental data or only

estimates. The distribution of the chemical is mainly

towards soil.

The RIRA (Table 4) shows that the risk for sec-

ondary poisoning is low. The relative risks for the re-maining compartments are of comparable magnitude

for the ready biodegradability scenario. Changing to

inherently biodegradable increases the relative risks for

water and sediment 10-fold.

No measured concentrations in the Netherlands for

this chemical are published. The use as pharmaceutical

for humans was 0.55 ton/yr in Denmark. Measured data

for German STP effluents and rivers report concentra-

tions below 50 ng/l (Hirsch et al., 1999), resulting PEC/

PNEC ratios are below one however the safety margin

with is only a factor of 10.

4. Discussion

4.1. PTB versus RIRA

The PTB criterion used in this study does not distinct

between the risks of the various chemicals evaluated;

all chemicals are classified as ‘low priority pollutants’

(Table 3).

For the RIRA, using EUSES for the calculations and

assuming a standard emission of 1 kg/d to the most

relevant environmental compartment, comparable input

Table 5

Reported measured concentrations of biphenylol in various countries

Location Concentration (lg/l) Reference

Water concentrations biphenylol

River Lee, England <0.1 HSDB

Delaware river 0.3 HSDB

Phoenix AZ, Sewage samples, USA <8 HSDB

Samples from water filtration plant 0.1–10 HSDB

Germany <1–95

Sanatoria wastewater, Germany 0.1–1

Ruhr river, Germany

Small lake close to superfund site, USA 100 Wick and Gschwend (1998)

Wastewater Cape Cod, USA 1 Rudel et al. (1998)

Eijsden en site ‘‘RT’’, The Netherlands 0.056 and 0.017 Leonards et al. (unpublished results)


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data are needed as for the PTB criteria together with

some estimated fate properties. The input-parameters as

well as results of the RIRA are on a gradual scale, in

contrast to the PTB-criterion. Therefore, the discrimi-

native value between compounds is higher and decisions

about which cut-off values have to be chosen are cir-

cumvented.

The relative risks for the six studied compounds are

given in Table 4 (see Fig. 1). In Fig. 2 for each com-

pound the relative risks are given for the water com-

partment, the soil compartment, and for worm-eaters

that represent the risk related to predators due to

biomagnification. A high figure means that a rela-

tively small emission can already create high risks. The

Fig. 1. Structural formulas of the compounds studied.


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maximum and minimum is given, representing the out-

come of the calculations with respectively worst case and

best case assumptions.

The relative risks for various environmental com-

partments differ strongly for some compounds (e.g. 5

orders of magnitude for both ivermectin and oxytetra-

cycline), while for other compounds the risks for the

different compartments are comparable. It can be di-

rectly seen what environmental compartment is most at

risk (bold figures in Table 4).Note that the RIRA gives a difference of 9 orders of

magnitude in the relative risks of the various studied

compounds (5:9Â 10À9 for worm-eaters and oxytetra-

cycline versus 5.5 for soil and ivermectin), while ac-

cording to the PTB-criterion all compounds fall in the

same class (low priority).

To gain more insight in the significance of the figures

for the relative risk, a comparison should be made with

well-known hazardous chemicals such as PCBs, dioxins,

heavy metals, etc. This was however not the purpose of

the present work.

4.2. Risks of the studied pharmaceuticals and disinfectants

The assumed standard emission of 1 kg/d is low; only

if chemicals are produced or imported in more than

1000 ton/yr (or 2739 kg/d) they are called ‘high-pro-

duction volume chemicals’ in the EU. Nevertheless

at this low assumed emission of 1 kg/d already a risk

is predicted for ivermectin, and an emission of 100

kg/d would result in impermissible risks for triclosan.

For ibuprofen and oxytetracycline an emission of

1000 kg/d would result in risks according to our calcu-

lations.

If figures on the actual use or emissions of the com-

pounds are available, the initial risks can be calculated

by multiplying the relative initial risk with the amount of

kilograms that is actually emitted or used. As the re-

gional scale was used in the EUSES calculations, im-

plying that modeled concentrations are comparable for

the whole region, locally the situation can be worse.

The relative risks of the chemicals studied vary by 5

and 9 orders of magnitude for the disinfectants and

pharmaceuticals, respectively. Therefore, disinfectantsor pharmaceuticals cannot be considered as homoge-

neous groups, in the sense that the risks of chemicals

within a group are comparable. In addition, the relative

risks of the compounds studied in the present work are

not necessarily predictive for risks of other disinfectants

or pharmaceuticals.

4.3. Use of experimental input data versus estimated input

data

For the PTB criterion, use of experimental data in-

stead of estimated properties resulted only in the case of ivermectin in a different classification (Table 3). For the

RIRA, using only estimated data or if possible experi-

mental data makes higher differences (Table 6). For

water, soil, and sediment, in the majority of cases the

use of estimated data only yields a lower relative risk

than using available experimental data. The highest

differences are obtained for oxytetracycline, up to 3.6

log-units. This is explained as the estimated K ow dif-

fers substantially from the experimental one. For other

compounds, the underestimation of the risk by using

only estimated data does not exceed one order of mag-

nitude. For the worm-eater and fish-eater instead, rela-

Fig. 2. Relative risks, assuming an emission of 1 kg/d, for three different environmental compartments.


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tive risks are equal or higher if only estimated data are

used.

5. Conclusion

For three examples of disinfectants and phar-

maceutical substances (biphenylol, 4-chloro-m-cresol

and triclosan as disinfectants and the pharmaceuticals

ivermectin, ibuprofen and oxytetracycline) a relative

initial risk assessment was performed assuming a stan-

dard emission. RIRA, as no information on actual use

or emission of the chemical is needed in contrary to a

normal initial risk assessment. In addition the hazard

of the compounds was evaluated based upon their

persistence, toxicity and bioaccumulative properties, the

so-called PTB-criterion.

The PTB criterion does not distinct between the risksof the various chemicals evaluated; all chemicals are

classified as ‘low priority pollutants’. The RIRA yield

a 9 orders magnitude difference in the relative risks of

the studied compounds (5:9Â 10À9 for worm-eaters and

oxytetracycline versus 5.5 for soil and ivermectin). The

relative risks for various environmental compartments

differ strongly for some compounds (e.g. 5 orders of

magnitude for both ivermectin and oxytetracycline),

while for other compounds the risks for the different

compartments are comparable. It is concluded that the

RIRA has a higher discriminative value and yields more

information compared to the PTB-criterion. To gain

more insight in the significance of the figures for the

relative risk, a comparison should be made with well-

known hazardous chemicals such as PCBs, dioxins,

heavy metals, etc.

The relative risks of the chemicals studied vary by 5

and 9 orders of magnitude for the disinfectants andpharmaceuticals, respectively. Disinfectants or pharma-

ceuticals cannot be considered as homogeneous groups,

in the sense that the risks of chemicals within a group are

comparable. In addition, the relative risks of the com-

pounds studied in the present work are not predictive for

risks of other disinfectants or pharmaceuticals. At the

low assumed emission of 1 kg/d already a risk is pre-

dicted for ivermectin, and an emission of 100 kg/d would

result in impermissible risks for triclosan. For ibuprofen

and oxytetracycline an emission of 1000 kg/d would

result in risks according to our calculations.

Acknowledgements

This work was prepared under authorisation of the

Dutch Ministry of Housing, Spatial Planning and the

Environment. Dick Sijm and Kees van Leeuwen criti-

cally read earlier versions of this manuscript.

Appendix A

See Table 7.

Table 6

Relative risks (logarithmic values); comparison of use of only estimated input data versus use of experimental data where possible

Water Soil Sediment Fish-eater Worm-eater

Disinfectants

Biphenylol K oc high À3.9 À3.4 À3.7 À4.7 À4.2

Biphenylol K oc low À3.8 À4.1 À3.8 À4.5 À4.9

Biphenylol all estimates À4.2 À4.3 À4.0 À3.8 À3.9

4-Chloro-m-cresol ready À5.4 À5.0 À5.4 À6.3 À6.6

4-Chloro-m-cresol inherent À4.3 À3.9 À4.2 À5.3 À5.6

4-Chloro-m-cresol all estimates À4.4 À5.3 À4.4 À4.2 À4.9

Triclosan inherent À2.0 À2.1 À1.8 À3.0 À1.3

Triclosan ready À3.0 À3.1 À2.7 À3.9 À2.4

Triclosan all estimates À3.7 À3.9 À3.5 À3.9 À2.4

Pharmaceuticals

Ivermectin inherent À0.6 0.7 À1.8 À3.5 À2.1

Ivermectin ready À2.2 À0.6 À3.5 À5.2 À3.4

Ivermectin all estimates À2.3 À1.0 À2.1 À3.8 À0.8

Ibuprofen inherent À4.8 À5.7 À4.7 À3.8 À2.6

Ibuprofen ready À5.8 À6.7 À5.8 À4.8 À3.7

Ibuprofen all estimates À3.7 À4.6 À3.7 À4.8 À3.8

Oxytetracycline ready À3.3 À3.6 À3.4 À7.0 À8.2

Oxytetracycline inherent À2.3 À3.5 À2.5 À6.1 À8.2

Oxytetracycline all estimates À6.9 À7.2 À6.9 À4.8 À6.1


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Table 7

Data on toxicity and environmental chemistry of the compounds studied

Parameter Experimental data Estimated dataa Reference

Biphenylol , C 12 H 10O1

Melting point 56 °C 87 °C (EPI) Mackay et al. (on-line)

Boiling point 275 °C 317 °C Mackay et al. (on-line)

Aqueous solubility 700 mg/l 536 mg/l Mackay et al. (on-line)

Vapour pressure 30 Pa 8.2e)3 Pa Mackay et al. (on-line)

Log K ow 3.09 3.28 Mackay et al. (on-line)

p K a 9.55 Mackay et al. (on-line)

K oc 1.03e4 l/kg Estimated EPI

120–1600 l/kg Estimated HSDB

Biodeg water DT50 Primary: days–weeks Estimated EPI

Degradation most important fate

process

Ultimate: weeks HSDB screening studies

Readily biodegradable

Real world: DT50 < 5 d Struijs and van den Berg

(1995)

Degrad in air DT50 OH radicals: Estimated EPI

0.39 dOzone: –

Aquatic toxicity LC50 fish: 6 mg/l DOSE

EC50 inv (Tetrahymena):

13.7 mg/l

EC50 microtox: 2.05 mg/l HSDB

EC50 Daphnia: 2.1–15 mg/l AQUIRE (n¼1)

EC50 fish: 6.1–14 mg/l AQUIRE (n¼1)

EC50 algae: 5 mg/l AQUIRE (n¼10)

NOEC algae: 350 lg/l AQUIRE (n¼3)

EC50 ciliate: 11 mg/l EC50 Daphnia: 0.71–2.1 mg/l

LC50 fish: 2.7–6.2 mg/l LC50 estimate: 6.77 mg/l

Acute mammalian toxicity LD50 mouse oral: 1050 mg/kg DOSE

LD50 rat oral: 2000 mg/kg HSDBLD50 cat oral: 500 mg/kg

Chronic mammalian toxicity NOAEL dogs 1 yr> 500 mg/kg/d HSDB

ADI: 0.02 mg/kg BW/d FAO/WHO (1990)

Carcinogenity Induces bladder tumors in rats DOSE

Mutagenicity

Teratogenicity Teratogenicity negative HSDB

Estrogen effects Xenoestrogen, and possible en-

docrine disruptor

DOSE

Bioaccumulation BCF fish: 47.79 l/kg Estimated EPI

4-Chloro-m-cresol , C 7 H 7 C 11O1

Aqueous solubility 3850 mg/l 699 mg/l Mackay et al. (on-line)

Vapour pressure 6.67 Pa 0.04 Pa Mackay et al. (on-line)

LogK

ow 3.1 2.70 Mackay et al. (on-line)and EPI exp. database

p K a 9.5 HSDB

K oc 717.6 l/kg Estimated EPI

Biodeg water DT50 Primary: days–weeks Estimated EPI

2% in 28 d Ultimate: weeks–months www.citi.or.jp

Readily biodegradable (aerobic

only)

HSDB

Degrad in air DT50 OH radicals: 0.417 d Estimated EPI

Ozone: – d

Aquatic toxicity LC50 fish: 4.6 mg/l www.citi.or.jp

LC50 fish: 0.01–0.1 mg/lb DOSE & HSDB

LC50 fish: 7.6–13 mg/l DOSE & HSDB

NOEC Daph: 1.3 mg/l HSDB


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Table 7 (continued )


LC50 fish: 1–2 mg/l HSDB

LC50 fish: 4.1–7.4 mg/l HSDB

LC50 Daphn: 0.17 mg/l RISKLINE

Inhib bact/fungi: 80–800 mg/l RISKLINE

IC50 nitr: 2–20.2 mg/l RISKLINE

EC50 prot: 23 mg/l RISKLINE

EC50 algae: 4.2–10 mg/l RISKLINE

EC50 Daph: 3.5–10 mg/l RISKLINE

NOEC Daphn repr: 1.25 mg/l RISKLINE

LC50 fish: 1–13 mg/l AQUIRE (n¼11)

NOEC fish: 1.0 mg/l

Daphn EC50/LC50: 1.9–6 mg/l AQUIRE (n¼1)

NOEC: 1.3 mg/l AQUIRE (n¼16)

Duckweed LC50: 96 mg/l AQUIRE (n¼6)

Fish LC50: 0.92–19 mg/l AQUIRE (n¼1)

Algae LC50/EC50: 10–15 mg/l LC50 estimate: 5.58 mg/l AQUIRE (n¼4)

NOEC: 1.9 mg/l

Xenopus EC50/lC50: 12–13 mg/lSoil toxicity EC50 lactuca: 32–100 lg/g DOSE

2.3 mg/l in nutrient sol

Acute mammalian toxicity LD50 oral rat: 1830 mg/kg DOSE

LD50 oral bird: >113 mg/kg HSDB

LD50 mouse oral: 710 mg/kg RISKLINE

LD50 21 360 mg/kg RISKLINE

Chronic mammalian toxicity NOEL subac rat: 200 mg/kg/d HSDB

NOAEL rat 90-d: 110 mg/kg/d RISKLINE

Carcinogenity Genotoxicity: positive and nega-

tive

DOSE

Mutagenicity HSDB&RISKLINE

Teratogenicity Mutagenicity: negative

No indications teratogenicity RISKLINE

Estrogen effects Positive (weak) Koerner et al. (1998a,b)Bioaccumulation BCF fish: 48.6 l/kg Estimated EPI

BCF fish: 5.5–13 l/kg www.citi.or.jp

Triclosan, C 12 H 7 C 13O 2

Melting point 56 °C 137 °C www.citi.or.jp

Boiling point 373.62 °C Estimated EPI

Aqueous solubility 17 mg/l 4.6 mg/l www.citi.or.jp

Vapour pressure 5.9e)4 Pa Estimated EPI

Log K ow 4.76 4.66 Experimental database

EPI

K oc 1.84 e4 l/kg Estimated EPI

DT50 in water Primary: weeks Estimated EPI

Ultimate: months

No degradation in 28 d www.citi.or.jpDT50 in air OH-radicals: 0.44 d Estimated EPI

Ozone: –

Aquatic toxicity LC50 fish: 2 mg/l www.citi.or.jp

LC50 fish: 0.25 mg/l AQUIRE (n¼1)

LC50 Daphnia: 0.39 mg/l AQUIRE (n¼1)

Hagioita et al. (1995)

IC50 act sludge bact: 6 mg/l LC50 estimate: 1.1 mg/l or

0.011 mg/l

Acute mammalian toxicity LD50 birds: 825– >2150 mg/kg AQUIRE (n¼2)

LC50 bird: >5000 mg/kg AQUIRE (n¼1)

Chronic mammalian toxicity NOAEL: 1 mg/kg/d Default

(continued on next page)


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Carcinogenity Negative Bhargava & Leonard

(1996)

Mutagenicity

Teratogenicity

Bioaccumulation BCF fish: 367.5 l/kg Estimated EPI

BCF fish: 2.7–90 l/kg www.citi.or.jp

Ivermectin, C 48 H 74O14

Melting point 349.84 °C Estimated EPI

Boiling point 943.48 °C Estimated EPI

Aqueous solubility 4 mg/l 1.4e)4 mg/l Bloom & Matheson

(1993)

Vapour pressure <2e)7 Pa 1.6e)28 Pa Bloom & Matheson

(1993)

Log K ow 3.22 4.95 Bloom & Matheson

(1993)

K oc 12 660–15 700 l/kg 1288 l/kg Bloom & Matheson

(1993)

4760 l/kg Halling-Sørensen et al.

(1998)

DT50 in water Primary: weeks–months Estimated EPI

Ultimate: recalcitrant

DT50 in soil Summer temp: 1–2 weeks Bloom & Matheson

(1993)

Winter temp: 52 weeks

Avermec B1A 14–56 d

Ivermec 6–240 d Halling-Sørensen et al.

(1998)

DT50 in air OH-radicals: 13 min Estimated EPI

Ozone: 13 min

Photodeg water Near surface 12–39 h Bloom & Matheson(1993)

Aquatic toxicity LC50 mar shrimp: 70 ng/l Davies et al. (1997)

Bloom & Matheson

(1993)

LC50 Daphnia: 25 ng/l

NOEC Daphnia: 10 ng/l

MATC Daphnia: 4 ng/l

LC50 fish: 3.3–5.3 lg/l

LC50 fish: 3–4.8 mg/l Halling-Sørensen et al.

(1998)

NOEC fish: 0.9 mg/l

EC x fish: 0.2–100 lg/l LC50 estimate:

0.67 mg/l AQUIRE (n¼7) (diverse

effects)Estimate Sijm (exp K ow)

Sediment toxicity LC50 mar amphipod: 0.18 mg/kg Davies et al. (1997)

LC50 starfish: 23.6 mg/kg

NOEC mortality: 0.05 and 5 mg/

kg resp.

Soil toxicity LC50 Eisenia: 315 mg/kg Bloom & Matheson

(1993)

EC weight loss <12 mg/kg

Acute mammalian toxicity LD50 birds: 85–2000 mg/kg Bloom & Matheson

(1993)

LC50 8 d birds: 383–3102 mg/kg Dossier

LD50 mouse: 12–40 mg/kg

LD50 rat: 43–53 mg/kg


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Chronic NOEL repro 18 months: Bloom & Matheson

(1993)

Mammalian toxicity >12 mg/kg

NOEL repre ratþmouse: 0.05

mg/kg/d

FAO/WHO (1993)

ADI for humans: 0.1 lg/kg/d Dossier

NOEL multigeneration: 0.2 mg/

kg/d

Temporary ADI: 0.2 lg/kg/d

Carcinogenity Carc/muta: Dossier (negative)

Mutagenicity Negative/positive (SCE) Aleksic & Baarjaktarovic

(1993)

Teratogenicity

Tera: positive (positive)

Dossier. Indirect: FAO/

WHO (1993) and Chaco-

nas & Smoak (1995)

Bioaccumulation BCF fish: 60.17 Estimated EPIBCF mussel: 750 l/kg l/kg Davies et al. (1997)

BCF fish (avermectin) 56 l/kg Van den Heuval et al.

(1996)

BCF fish: 28–84 l/kg AQUIRE (n¼3)

Ibuprofen, C 13 H 18O 2

Aqueous solubility 2440 mg/l 41 mg/l HSDB

Vapour pressure 0.0248 Pa Estimate EPI

Log K ow 3.97 3.79 Experimental EPI

p K a 5.2 HSDB

5.7 Stuer-Lauridsen et al.

(2000)

K oc 394.3 l/kg Estimate EPI

K p in sludge 251 l/kg Stuer-Lauridsen et al.

(2000)

(prelim K oc 717 l/kg)

Biodeg water DT50 Primary: days Estimate EPI

IB and metabolites >95% Ultimate: weeks Buser et al. (1999)

Degr in STP Ternes et al. (1998)

Incomplete degr in STP Halling-Sørensen et al.

(1998)

Inherently biodegradable

Degrad in air DT50 OH radicals: 0.90 d Estimated EPI

Ozone: – d

Aquatic toxicity Min Inh Conc fungi/bact. 5–150

mg/l

Halling-Sørensen et al.

(1998)

Microtox EC50 12.3 mg/l

EC50 algae: 7.1 mg/lNEL algae: >30 mg/l

EC50 Daphnia: 9.1–12 mg/l

NOEC Daphnia: 3 mg/l

LC50 fish: 173 mg/l

NOEC fish: 10–30 mg/l

LC50 estimate: 1.89 mg/l

Acute mammalian toxiocity LD50 oral rat: 636 mg/kg DOSE

LD50 oral mouse: 740 mg/kg

Carcinogenity Teratogenicity: not See e.g. Ostensen &

Ostensen (1996)

Mutagenicity Ostensen (1994)

Teratogenicity Randall et al. (1989)

(continued on next page)


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Estrogen effects Interaction at estrogen receptor Sibonga et al. (1998)

Bioaccumulation BCF fish: 3.162 Estimate EPI

Oxytetracycline, C 22 H 24 N 2O9

Aqueous solubility 1.87e5 mg/l Estimate EPIDependent on pH DOSE

Slightly soluble HSDB R9

Vapour pressure 1.22e)20 Pa Estimate EPI

Log K ow À0.90 À2.87 Experimental and

estimate EPI

p K a Several charged moieties in mol-

ecule

Stuer-Lauridsen et al.

(2000)

K oc 97.2 l/kg Estimate EPI

Experimental K p sludge: 3020

l/kg (prelim K oc: 8630 l/kg)

Stuer-Lauridsen et al.

(2000)

Biodeg water DT50 Primary: weeks Estimate EPI

Ultimate: months

Degrad in air DT50 OH radicals: 0.040 d Estimate EPI

Ozone: 0.50 d

DT50 sediment DT50: 10 week DOSE

DT50: 87–144 d Samuelsen et al. (1992)

Anaerobic: inf. 9–419 d Lai et al. (1995)

Halling-Sørensen et al.,

1998

Aquatic toxicity EC50 nitrif: 8.6–27 mg/l Klaver and Mathews

(1994)

LC50 fish: 75–150 mg/l

LC50 crus: 61 lg/l–102 mg/l AQUIRE (n¼6)

AQUIRE (n¼11)

NOEC crus: 55–161 lg/l

Algae misc: 2 mg/l AQUIRE (n¼5)

EC50 algae: 27 lg/l AQUIRE (n¼6)NOEC fish: 447 mg/l Holten-Lutzhoft et al.

(1999)

LC50 estimate: dep. on chem. Bumguardner & King

(1996)

class: 143–1.1e5 mg/l

Soil toxicity Effects on plants at 160 mg/l

solution

Halling-Sørensen et al.

(1998)

Acute mammalian toxicity LD50mouse: 2240 mg/kg DOSE

LD50 rat: 4800 mg/kg DOSE

LD50 birds: >2000 mg/kg AQUIRE (n¼1)

AQUIRE (n¼2)

LC50 birds: >5620 mg/kg

Chronic mammalian toxicity RfD¼1 mg/kg/d HSDB

Carcinogenity Carc: negative (in vitro positive) DOSE, Dietz et al. (1991)Mutagenicity

Teratogenicity Carc: suspected (sister chroma-

tid)

Dossier

HSDB

Carc: equivocal evidence in rats Dashe and Gilstrap (1997)

Terat: negative HSDB

Pos evid of human fetal risk

Estrogen effects Interaction with hormone me-

tabolism

Hamalainen et al. (1987)

Bioaccumulation BCF fish: 3.16 l/kg Estimate EPI

BCF bivalves: 0.24–0.63 l/kg AQUIRE (n¼3)

a Estimated by EPIWIN, unless otherwise stated.b

This value is ignored, as it is contradictive to the other results.


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