3. English summary, Miljøstyrelsen

Litteraturudredning vedrørende human medicin i miljøet

3. English summary

Prior to their introduction to the Danish market pharmaceuticals are not assessed with respect to their environmental properties or the consequences for the environment of their use. The present project is a literature investigation of the potential for effects and accumulation of pharmaceuticals in the environment from recommended therapeutical use of pharmaceuticals for human use.

A total of 4103 pharmaceuticals with 999 different active compounds were on the Danish market in 1997, but only for a few is data available to allow for evaluation with respect to environmental properties. The first-hand screening has been based on information on the consumption of pharmaceuticals and general information on their mode of action for groups of pharmaceuticals and individual pharmaceuticals.

Evaluation of the relative importance of groups of pharmaceuticals (ATC groups) has been based on the consumption of each group, estimates of conversion factors on group level, and special attributes of the ATC group.

The statistic of the 25 most used pharmaceuticals (L25) from the Danish Medicine Agency has been used for evaluation based on the consumed amount.

Pharmaceuticals are identified as potentially problematic for the environment if they are used in large amounts and/or only needs a minor dose to accomplish the therapeutic effect in humans ("high biological activity").

Table 3.1
Overview of the assessment of ATC groups and identification of pharmaceuticals that may be problematic. Compounds in parenthesis are on L25, but in groups that cannot be assessed.

ATC group	Group	Environmental evaluation	Pharmaceuticals that may be problematic
A	Alimentary tract and metabolism	No environmental effects expected	-
B	Blood and bloodforming organs	No environmental effects expected	-
C	Cardiovascular system	Possible environmental effects	Furosemide Bendroflumethiazide
D	Dermatologicals	Cannot be assessed	(Ketoconazole)
G	Genito urinary system and sex hormones	Possible environmental effects	Estrogens
H	Systemic hormonal preparations, excl. sex hormones	Cannot be assessed	(Corticosteroids)
J	General antiinfectives for systemic use	Possible environmental effects	Various antibiotics
L	Antineoplastic and immunomodulating agents	Possible environmental effects	-
M	Musculo-skeletal system	Possible environmental effects	Ibuprofen
N	Nervous system	Possible environmental effects	Paracetamol Several compounds cannot be assessed
P	Antiparacitic products, insecticides and repellants	No environmental effects expected	-
R	Respiratory system	Cannot be assessed	-
S	Sensory organs	No environmental effects expected	-
V	Various	No environmental effects expected	-

The general conclusions drawn in this report on ATC groups and specific pharmaceuticals have been based on limited data set, and is has been necessary to make a number of assumptions on the potency, degradability and fate in the environment to facilitate an assessment. The following have formed the basis for the assessment

the list of the 25 most used pharmaceuticals (L25),

that the pharmaceutically active ingredient is also the environmentally active compound, and

that the "worst case" for the aquatic environment is the situation where no degradation, sorption or dilution takes place.

The assessments given here are based on normal therapeutic doses and even distribution patterns spatially and temporally. They should not be used for final evaluation of the environmental risks associated with the use of pharmaceuticals or groups of pharmaceuticals. The assessment is to be interpreted as a screening exercise identifying areas of no apparent concern and of pharmaceuticals that may be candidates for potential environmental effects, possibly leading to a closer investigation.

Toxicity data on the compounds of the L25 and other pharmaceuticals have been searched in reviews, databases, and in the scientific literature, but have only been identified on a limited number of pharmaceuticals. In all, data on concentrations of 24 individual pharmaceutical and metabolites in the environment are presented, together with the available data on ecotoxicological test (17 compounds). Data on degradability in the environment and octanol-water coefficient are given 48 compounds. These data have been included in the assessments where possible.

For 20 pharmaceuticals on L25 the temporally and spatially average concentration in waste water have been calculated under assumptions of "worst cases" for the pharmaceutical:

there is no metabolism in man

there is no degradation in sewage treatment plants

it is the active form which is emitted

no dilution is included

the pharmaceutical is only present in the water phase

The risk quotient, which is the result of the estimated or measured concentration in waste water is compared to the estimated concentration in the environment without effect (predicted no-effect concentration, PNEC), and the resulting risk quotient is shown in Table 3.2. A value above one is environmentally problematic.

Table 3.2
Overview of the assessment of pharmaceuticals according to the effect and estimated or measured exposure, possibly leading to a closer investigation.

Pharmaceutical	Risk quotient
Pharmaceutical	Estimated mean concentration in waste water/PNEC	Measured concentration of pharmaceutical/PNEC
Acetylsalicylic acid	0.15	0.025
Estrogens (standard tests)	0,017	0,0049
(non standard tests)	3,581	1,000
Ibuprofen (standard tests)	5,0	0,36
(non standard tests)	9	0,67
Paracetamol (standard tests)	2,8	No measurements
(non standard tests)	41,2	No measurements

Two candidates for potential environmental problems from the ATC group for Cardiovascular system (furosemide and bendroflumethiazide) are both used in large amounts, but there was insufficient data to assess the compounds.

Attention is drawn to the fact that none of the data sets of measured concentrations are from Denmark and both local and regional differences may affect the emission pattern.

In the project no data on sorption properties or toxicity of pharmaceuticals in soil have been identified, which could be used for assessment of toxicity in soil environment. Several of the pharmaceuticals on L25 have a potential for sorption to sludge, and the degradability in soil or sludge is not known or poorly investigated.

The consumption of pharmaceuticals in hospitals is not included in the statistic. Emissions from hospitals and other treatment centres may act as point sources presumably with higher concentrations of pharmaceuticals and metabolites compared to the average occurrence in wastewater.

Generally, the concentrations found in the environment and other sources of non-therapeutic exposure are considerably below the therapeutic doses, normally administered to humans. This does not, however, exclude the possibility that there may be relevant exposure scenarios leading to fx. long term or combination effects, or effects to vulnerable groups.