Comparative and Veterinary Pharmacology

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maximum measured concentrations of these compounds in surface waters with
PNECs for the study compounds, obtained from regulatory type studies, it is
possible to obtain an indication of the potential risks these compounds pose to the
UK environment. Maximum measured concentrations for all of the antibacterial
compounds studied (oxytetracycline, sulfadiazine, trimethoprim and lincomycin)
were at least an order of magnitude lower than their PNECs (Table 1 ) indicating
that these substances do not pose a great risk to the environment. Concentrations of
the parasiticides studied were below analytical LODs. As the LODs were either the
same as or lower than PNECs, the data indicate that these also are unlikely to be a
major concern in the water compartment (Table 1 ). However, many scientists are
now questioning the suitability of standard regulatory studies for assessing the
environmental risks of veterinary medicines and advocate the use of other more
subtle and chronic endpoints.


5.2 Chronic and Subtle Effects

As veterinary medicines are biologically active substances, concerns have been
raised over the relevance of the acute standard ecotoxicity studies that are employed
as part of the registration process. The main concern is that if the target receptor for
the veterinary medicine also occurs in an organism in the environment, it is possible
that the compound will have a much more significant impact on the environment
than indicated by the acute bioassays. Many scientists therefore advocate that
chronic endpoints and more subtle endpoints should be investigated. Table 2 lists
a number of studies that have investigated some of these endpoints and in the
following section, some examples of studies exploring the chronic as well as more
subtle impacts of veterinary drugs are described. Severe environmental impacts of
veterinary drugs, that would not have been detected based on standard regulatory
studies, are also discussed.


Table 1Comparison of maximum measured environmental concentrations with predicted no-
effect concentrations obtained using regulatory ecotoxicity studies for veterinary medicinal
products (Data taken from Boxall et al.2006a)
Veterinary
medicine


Most
sensitive
species

Effect
endpoint
(mg/L)

Predicted no-
effect
concentration
(mg/L)

Measured
concentration
(mg/L)

aRisk
characterisation
ratio

Oxytetracycline Green algae 4.5 45 4.49 0.10
Sulfadiazine Green algae 3.49 34.9 4.13 0.12
Trimethoprim Green algae 16 1.6 0.02 0.001
Ivermectin Daphnids 0.000025 0.00025 <0.0002 <0.8
Doramectin Daphnids 0.0001 0.001 <0.001 < 1
Lincomycin Daphnids 379.4 379.4 21.1 0.006
aRisk characterisation ratio ¼ measured environmental concentration/predicted no-effect


concentration


304 A.B.A. Boxall

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