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Critical discussion of the current environmental risk assessment (ERA) of veterinary medicinal products (VMPs) in the European Union, considering changes in animal husbandry

Abstract

Background

Veterinary medicinal products (VMPs) administered to livestock might affect the environment. Therefore, an environmental risk assessment (ERA) is conducted during the approval process of VMPs. In the European Union (EU), the ERA, which was established approximately 10 years ago, consists of two phases. In the present review, we examined the first phase. In this phase, VMPs are subjected to a decision-making process comprising 19 questions and several tables with default values published in the “Guideline on environmental impact assessment for veterinary medicinal products in support of the VICH guidelines GL6 and GL38 (European Medicines Agency 2016).”

Since a proportion of livestock husbandry systems is currently shifting toward ecological husbandry and free-range production systems, there is a lower risk of VMP consumption in general, but livestock excretions possibly containing VMPs might be directly released into the environment instead of being stored and applied as manure. In the present study, the first phase of the current ERA of VMPs in the EU was critically discussed with respect to the changes in animal husbandry. The large number of default values used in the ERA were checked for topicality. In a three-step approach, firstly trends and changes in animal husbandry in Europe that might be relevant for the ERA were collected, secondly, the interactions between Phase I and animal husbandry were evaluated and thirdly, the default values used in Phase I were verified in order to identify research gaps.

Results

Several default values used in the current ERA were identified as outdated. Together with the lack of valid data (e.g., on animal husbandry systems or VMP treatments), this may have an impact on the predicted environmental concentration (PEC) as the central decision threshold of the ERA.

Conclusions

The results of the present study indicate that an update of the ERA of VMPs in the EU is required to consider the changes in animal husbandry. Several aspects related to this issue are critically discussed.

Background

The release of active substances or metabolites from veterinary medicinal products (VMPs) getting into the environment can impact the health of humans, animals, and other non-target organisms. Since most environmentally toxic VMPs are excreted predominantly unchanged, such as sulfonamides, tetracyclines, and avermectines [1, 2], excretions are the main path of their entry into the environment.

The most harmful veterinary drugs that enter the environment include antibiotics, antiparasitics, and hormonally active substances [3]. Only the use of antibiotics has been decreasing in Germany since the revision of the German Medicinal Products Act in 2014 (prescribed quantities 1706 t in 2011 and 670 t in 2019) and might be reduced further in the future [4]. However, a minimal level of necessary VMP treatments will likely persist to safeguard animal welfare Thus, the assessment of VMP entry pathways into the environment is necessary. Some of these VMPs are hardly degradable and accumulate in the environment, hence promoting the development of resistances or affecting non-target organisms [5, 6]. The environmental impact of VMPs ranges from immediate toxicity for environmental organisms to long-term consequences such as altering populations or restricting growth, as shown in laboratory experiments [7,8,9,10,11]. Additionally, the combined effects of several substances and multiple exposures from different sources may also be essential [12]. Organic fertilizers obtained from farms rearing or to a lesser extent fattening poultry or pigs can be highly contaminated [13, 14]. Tetracyclines and sulfonamides have previously been detected in high amounts (mg active substance per kg sample) in pig manure as well in soil fertilized with pig manure [15,16,17].

The residues of veterinary drugs are incorporated into the soil to different extents, depending on their degradation behavior and their ability to adsorb to organic and inorganic matter [18]. Higher half-lives of VMPs are always associated with higher residue concentrations. A higher adsorption tendency results in higher residues in the top soil layer. Because VMPs stay at the surface and fail to seep quickly into the deeper soil layers, those present in the top layer might enter into the surface water via runoff. Lower adsorption affinity, conversely, promotes entrance into the groundwater. Furthermore, VMPs can have negative ecotoxicological consequences for terrestrial and aquatic organisms [4].

The exposure analysis of substances plays a significant role in the environmental risk assessment (ERA) of veterinary drugs, as it is pivotal for the calculation of the theoretically expected concentrations of substances in the environment (predicted environmental concentration, PEC). The ERA of VMPs is based on their PEC in soil (PECsoil), surface water (PECsurface water) and ground water (PECground water) [19]. Based on the ERA, if there are no risks identified the VMP is approvable. If there are risks identified, the applicant has to propose risk mitigation measures (RMM). If the RMM are not enough to eliminate the risks, then the environmental risks (together with other risks) will be weighed against the benefits of the VMP. If the benefits outweigh the risks, the VMP is still authorized. VMPs containing two or more active substances (fixed combination products) also undergo an evaluation process [20].

The calculation models and input values currently used by the European Medicine Agency (EMA) for the ERA of VMPs are more than 10 years old [21]. The current ERA does not allow adjustments for recent structural changes in animal husbandry and agriculture, such as the significant elevation of free-range husbandry due to increased ecological production and animal welfare standards. An increase in free-range husbandry may lead to lower VMP consumption in general, but in case of application of VMPs are more likely administered on pasture instead of in a stable. Therefore, more punctual contaminations are expected on pasture. Consequently, residues of VMPs are released into the environment in a more uncontrolled and direct manner compared with animals kept exclusively in the stable.

This study aimed to critically discuss the first part (Phase I) of the ERA of VMPs from the animal husbandry perspective. A three-step approach was used: (1) collection of trends and changes in animal husbandry in Europe that might be relevant for the ERA; (2) evaluation of interactions between Phase I of the ERA and animal husbandry and (3) verification of the default values used in Phase I and identification of research gaps.

Principles of the ERA for VMP market approval

Figure 1 shows the ERA for VMP market approval focusing only on the ERA of VMPs used in terrestrial species. The decision process is organized in a two-step approach, whereby each potential VMP undergoes Phase I first. Only if the decisions based on questions 1–19 of Phase I lead to Phase II, the potential VMP will need to be tested in more detail. The calculations reflect the models for the exposure scenarios and different default values for, e.g., each animal species. The default values are mostly shown in Tables 1, 2, 3, 4, 5, 6 of the environmental impact assessment (EIA) guideline for VMPs, in support of the Veterinary International Conference on Harmonization (VICH) guidelines GL6 and GL38 (VMP guideline) [22]. Additional file 1: Tables S1–S6 summarize all calculations and original tables that might be necessary for understanding the results of this discussion.

Fig. 1
figure1

Overview of the decision tree for VMP market approval according to the EMA [22] and the associated tables, which were examined to verify actuality from the perspective of animal husbandry

Categorization of livestock in the ERA

The categorization of livestock plays an essential role in the market authorization of a VMP [23].

Because diseases and treatments appear to vary with animal age and the husbandry system [24, 25], categorization is an essential factor for risk assessment. Presently, according to VMP guidelines [22], categorization is based on age (young vs. adult) and production purpose (breeding vs. fattening). Several overlaps or gaps were encountered which could be resolved by adapting the categories appropriately. All animal types in relation to their total number in Germany and their body weights in livestock units (one livestock unit = 500 kg live weight) were analyzed as part of this study (Fig. 2). Animal types were considered independent of their categorization to major or minor species (Fig. 1, Phase I, question 4) [22]. The extensive analysis of 52 German and EU regulations (Additional file 1: Table S7) as part of this study revealed that several production animals are inconsistently categorized. An example of overlapping categories is “calves”. Although “calves” are defined as cattle up to the age of 6 months, this category partly includes the category “cattle aged zero to one year” [22]. To resolve this overlap, “calves” could be defined as all newborn and young bovine up to the age of 6 months and be therefore clearly separated from the category “cattle aged six months and older”. The category calves also includes veal and suckler calves, as defined in national regulations [26]. Beef cattle in the age group of 6 months and above could be summed up in one category. It would make sense to clarify the assignment of heifers, suckler cows, and calves from suckler cow husbandry to the categorization of beef cattle and delete the term “beef”, because all these animals will not get intramammary treatments or be dried off with a VMP, for example. Among dairy animal types, the category “mother including pup” does not match the current husbandry systems because of the separation of the pup from its mother immediately after birth; therefore, a new category “pups from birth onward” would be appropriate. Consequently, all pup categories should start at weaning.

Fig. 2
figure2

Systematic categorization of animal types, with the slice size illustrating the number of animals in livestock production units based on statistical numbers in Germany. Circles represent different levels: animal species (the inner circle), production branch (the middle circle), and animal type (the outer circle). Colors indicate the proportion of animals exclusively kept in stables (black, 100%) or on pasture (light grey, 0% in stable). Data were obtained from the Statistical Office of the EU (Eurostat) [61,62,63,64,65,66,67,68,69,70], Federal Statistical Office of Germany [34, 49, 54], Federal Office for Agriculture and Food [33, 55], Federal Ministry of Food and Agriculture [56, 57], and personal communication with E. Zumnorde-Mertens at the German Equestrian Federation (FN) and with T. Roettger at the Damwild Farming Mitte-West e.V. via telephone

Changes in animal husbandry and relevance for the ERA

Figure 2 also shows the proportion of animals reared on pasture, which is addressed in Phase I assessment in question 15 of the VMP guideline (Fig. 1).

Cattle

The animal type “dairy cow”, as listed in original Tables 3, 4, 5, 6 of the VMP guideline, should clearly include or exclude heifer and suckler cows, whereby the category “calves” includes calves for dairy replacement as well as for veal or beef production. Calves raised in suckler cow production systems are currently neglected, but they represent a considerable proportion of the whole calf production. Suckler cow production systems are mainly established on pasture. The category “other cows” represent mainly suckler cows or rare breeds, which are all predominantly kept on pasture. In Germany approximately 650,000 cows belong to that category, representing up to 14% of all cows in comparison to more than 4 million dairy cows in Germany [61]. The proportion of suckler cows with 14% is too high to neglect their husbandry system.

Heifers are also partly raised on pasture. The housing factor is 1 for animals housed throughout the year in the stable and 0.5 for animals housed indoors for only 6 months and on pasture for the rest of the year. It fails to mirror some current husbandry systems including those with permanent access to stable and pasture, and daily access to pasture for a few hours. Thus, we suggest that an additional factor (pasture-to-stable ratio; Table 3) should be considered, which reflects the exposure routes shared between manure and direct entries on the pasture.

Pigs

Pig production occurs mainly in enclosed stables and almost never on pasture [21], and given the risk of African swine fever infection, this practice will likely continue in the future. Boars are increasingly used for fattening because of the obligation for pain relief during castration in Germany and in other European countries [27, 28]. Boars differ from other fattening pigs in N retention and excretion, which results from of differences in their growth and feed conversion [29, 30]. Thus, either boars should be categorized as an additional animal type, besides females and barrows, or the default values for “nitrogen produced per place and year” should be changed to a slightly higher value (1 kg N year−1) for all fattening pigs. The differentiation between breeding systems of boars and sows could be skipped, as breeding facilities keep only a small number of boars, and the number of farms harboring numerous boars for breeding purposes is also low. Therefore, the category “breeding boar” could be neglected. Accordingly, the category “sow” could be defined as “breeding pig”, which includes sows with suckling litter as well as a few boars for breeding.

Poultry

In the case of poultry, the current categorization can be maintained because it follows the established categorization by species. However, because of the increasing number of laying hens on pasture [31, 32] or in husbandry systems with access to pasture, the exposure routes seems to be mixed between manure production within a stable and direct entries on the pasture as described for cows. Therefore, we recommend using the suggested additional factor pasture-to-stable ratio (Table 3). This accounts for a non-neglectable amount of animals, including animals of free-range husbandry systems with a proportion of 18.4% in Germany and 15.3% in the EU in 2019 [33, 34]. Additionally, ecological husbandry requires access to free-range poultry, which accounts for 11.5% of all laying hens held in Germany and 5.1% of those in the EU [33,34,35], so the estimated proportion of laying hens housed predominantly free-range consisting of the sum of free-range and ecological husbandry is about 25%. Additionally, other birds such as geese, quails, and ostriches are frequently reared free-range, with access to surface water in some cases. This is not addressed in the current ERA. Overall, we propose that the original VMP guideline Table 1 [22] should be amended with checkmarks.

A more detailed description of these husbandry systems is necessary because the number of free-range husbandry systems is increasing and the separation between indoor and outdoor husbandry systems does not reflect the entry of VMPs into the environment. Furthermore, some husbandry systems for pigs and poultry, designated as “outdoor”, do not provide any route for the direct entry of VMPs into the environment because the outdoor yards are covered with concrete floor. Similarly, the term “intensively reared” is mainly associated with animals kept in stables, but also applies to outdoor systems. In the ERA, differentiation should be made between solid floor and unpaved surface. Currently, the calculation of PECsoil initial for animals reared free-range relies only on stocking density (Eq. 2, VMP guideline, [22]). Dung dropping behavior should be researched and considered for free-range husbandry, such as rank patches [36, 37]. It might be worthwhile to distinguish between terrestrial and aquatic birds, to account for access to water. Some species such as ducks are almost completely reared outdoors, with access to water, which suggests that the direct VMP entry into water is possible (original VMP guideline Table 1 [22]).

Horses

The majority of horses (> 90%) are raised for sport and leisure activities so that their owners can avoid the additional effort involved in documentation, which is required for maintaining the food production status of equine species in Germany. The status of being a VMP-treated food-producing or non-food-producing animal (question 3, [22]) seems to be irrelevant for an ERA because companion animals also dump their droppings on pastures or pasture-like surfaces, especially in residential areas [38]. Horses are included in the ERA, although they are almost exclusively categorized as non-food species in Germany. Since substantial amounts of VMPs are also administered to companion animals [39, 40] as well as other non-food species, and to the best of our knowledge, data on the proportion of feces disposed of via residential trash are warranted [41, 42]. A justification for the exclusion of non-food species from the ERA is missing, thus opposing a risk-oriented approach.

Small ruminants

Dairy goats are increasingly being reared intensively in some production systems [43,44,45], so that they might be added to Tables 3 and 6 of the VMP guideline. Trends for indoor husbandry seen for dairy goats seem to be similar for dairy sheep [46,47,48]. Besides small ruminants, deer should be added as another category as they are increasingly being used in intensive outdoor husbandry systems. Direct entry of VMPs into water most likely also applies to small ruminants and equine in case of external application [49], but is unclear for systemic treatments since information about defecation behavior in water is missing. To maintain consistency in the wording used in Table 1, we suggest using the plural for goats as for all other animal types. Analogous to the additions to the original VMP guideline Table 3 (intensively reared animals), we suggest adding the categories “boars”, “dairy goats”, and “dairy sheep” to the original VMP guideline Table 6 and to fill the rows with values (table not shown).

Other species

The category “others” in Fig. 2 includes insect species such as bees, black soldier flies or mealworms. On the basis of the current use of insects as (novel) food for humans or feed for livestock, these new production animal species might be intensively reared on specialized farms [50,51,52]. Because of the completely different pathways and husbandry systems [53], the environmental impact assessment for insects should be developed completely decoupled from that for the existing terrestrial livestock branches and aquatic production systems.

Exposure routes

Table 1, which is based on the original VMP guideline Table 1 [22], shows the predominant exposure routes of veterinary medicines in key livestock species and compares the original EMA data with Montforts [21].

Table 1 Predominant exposure routes of veterinary medicines in terrestrial key livestock species

The original VMP guideline Table 2 [22] describes the proportion of herd or flock treatment for various groups of VMPs. To differentiate between the route of exposure and the husbandry system, the column headings of the original VMP guideline Table 2 [22] should be revised as shown in Table 1. Considering the route of application, the term “slurry” might be replaced by a more general term that includes all excretions used as organic fertilizer. This includes all kinds of feces with or without bedding material such as poultry litter or solid manure of hoofed and clawed animals since they represent all husbandry systems in which excretions can be collected on concrete (without direct environmental entry), stored, and uniformly applied as organic fertilizer. The term “grazing animals” refers to a husbandry system in which animal feces directly enter the environment without any storage. This occurs regardless of the surface type, predominantly on pasture but especially in free-range poultry and small ruminant husbandry systems, where grass might be lacking [58]. All environmental entries, besides the excretions of animals, are included in the two remaining categories “loss at application/exposure outdoors” and “direct entry into water”.

Data collection

The ERA for market approval should strike a balance between benefit and effort, as described by Montforts [21]. However, a higher number of categories requires the analysis of an equally higher number of scenarios and the preparation of more detailed information. Animal numbers are recorded in different ways in Germany and the EU. Not all animal species are subject to the same reporting requirements within the German federal states. The German federal states report to the Federal Statistical Office destatis, which forwards the data to the statistical office of the European Union called Eurostat. Due to different recording periods as well as minimum recording limits with regard to animal numbers per farm, there may be considerable differences in the data here. Data collection periods and limits should be harmonized as a matter of urgency in order to minimize these discrepancies (Haupt et al., unpublished manuscript).

Animal husbandry: regional differentiation between European countries

Over years the question arose if differences in livestock production systems exist among European countries as it is known from the exposure assessment of plant protection [59, 60] that should be reflected in a future ERA of VMP. Neither animal density nor average herd size showed a consistent pattern that could allow the construction of model regions within the EU. Additionally, within Germany (as an example), regions displayed a high intra-diversity. Overall, a detailed comparison was not possible because of the lack of standardized and systematic data. Thus, data from 2013 were used in this study to estimate the animal density (number of animals per km2) and average herd size (number of animals per farm) for each country (Fig. 3). Hence, we advise against the differentiation of Europe into territorial areas as in Regulation (EC) No. 1107/2009 [59] when reviewing the VMP exposure scenarios.

Fig. 3
figure3

Farm animal density (A, C, E) and average herd size (B, D, F) in Europe. Densities of cattle (A), pigs (C), and poultry (E) calculated by dividing the number of each animal species in each country by the geographical area of the respective country (km2). All 28 EU states (including Great Britain) were considered. Average herd size of cattle (B), pigs (D), and poultry (F) calculated by dividing the number of each animal species in each country by the number of farms in the respective country [31, 61,62,63,64,65,66,67,68,69,70,71]

Proportion of herd treatment for various VMP groups

Generally, for most groups of VMPs, it is assumed that the entire herd is treated [22]. However, for most VMPs, particularly anthelmintics, individual treatments are preferable [72]. Reducing the use of VMPs such as by applying selective deworming strategies is gaining importance and increasingly being implemented in livestock production systems. Monitoring antibiotic treatments and resistance [73] as well as a more detailed diagnosis before the treatment have increased awareness and decreased the proportion of animals treated with antibiotics [74, 75]. A good scientific practice is to treat each animal individually and abstain from entire (100%) herd treatments. Nonetheless, some oral VMPs are still commonly administered with feedstuff or drinking water to the entire herd or respective flock in some cases [76,77,78]. The selective administration of VMPs via feed or water, especially in pig and poultry production systems, requires complex and expensive solutions such as switch points in pipe systems to limit VMP application to each compartment [79]. Besides the primary goal of improving animal health, it would be favorable to further reduce the unnecessary application of VMPs by promoting these technical solutions and individual treatments in general. The shift from oral administration to individual application will likely be reflected in VMP groups and the proportion of herd treatment.

In dairy cow husbandry, the commonly used dry-off treatments containing antibiotics are increasingly being questioned and replaced by antibiotic-free products or management strategies [80,81,82,83,84]. For intramammary preparations containing antibiotics, it is currently assumed that the entire herd is treated, but in fact, not the entire herd will be dried off; for example, heifers with no previous lactation, cows who had an abortion during the lactation period, cows who are continuously milked and cows without a dry-off period that will be sold to the slaughter. Assuming a replacement rate of 25–40% [85,86,87] and as shown in the model of Montforts [21], we suggest reducing the value for herd treatment of intramammary preparations in the original VMP guideline Table 2 [22] to 75%. Even if heifers are excluded from the category “cow”, their number most likely mirrors the number of cows for slaughter, where treatment will be avoided to decrease the input cost and withdrawal times. However, intramammary preparations containing antibiotics are not included in the national German antibiotic monitoring. They are either used for treatment of mastitis or drying-off, whereby following good practice antibiotics should only be used to treat an actual infection. The unacceptable connivances of antibiotic applications are enhanced by monetary factors, as antibiotic preparations are cheaper than preparations of antibiotic-free sealants. Consequently, intramammary preparations are often administered prophylactically and for financial reasons, which should be strictly reduced in the future. Thus, a proportion of antibiotic dry-off herd treatment can be partly substituted by sealants in the future. It is also predicted that the number of herd treatments with certain product groups, such as anthelmintics, coccidiostats, and antibiotics, will decrease within the next few years because of the recent regulatory changes [88]. Thus, we suggest collecting data on the use of the respective groups during the next few years and evaluating the proportion of herd treatments based on reliable data in the future (Table 2). Another relevant factor is that the performance of dairy cows partly depends on the number of milkings per day (Table 6), influencing the frequency of administration of teat dips and sprays at milking. Automatic milking systems enable more than 2.5–3 milkings per day [89]. Considering the proportion of dairy herds with automatic milking systems, together with some other dairy farms capable of 2–3 milkings per day, we suggest increasing the number of milkings per day as a default value of PECsoil for dairy cattle teat dips or sprays (Eq. 3, [22]) from 2 to 2.5.

Table 2 Proportion of herd or flock treatments for various groups of VMPs of the EMA guideline, with suggestions for an update

Foot rot in sheep is a common disease in which the entire herd is usually treated. It is possible to treat foot rot by injectable antibiotics or footbath. Since injectable antibiotics are already covered by original VMP guideline Table 2, we recommend changing “foot rot in sheep” to general “footbath” since increasing the appearance of digital dermatitis in bovine species leads to the usage of footbaths with comparable active agents in all ruminant species [90,91,92,93]. Currently, footbaths are applied only at the herd level.

The suggested changes for the original VMP guideline Table 2 [22] are included. Based on the increasing implementation of reduction strategies, as described in the listed literature [80,81,82,83, 94,95,96,97,98,99,100,101,102,103,104,105,106] and unpublished personal observations, in many cases, the proportion of herd treatment is expected to be lower than the current default values in the guideline [22]. This gives certainty that, regarding herd treatment, the exposure of the environment would currently not be underestimated. If reliable data on the percentage of herd treatment are collected within the next few years, lowering some default values could be considered where major changes have occurred because of new legislation or treatment guidance.

The ERA of many treatments of “a small number of animals” ends at Phase I (question 5 [22]), except for injectable antibiotics (used in pigs, to treat respiratory disease in cattle and to treat foot rot in sheep) as well as hormones, which have a zootechnical use [22]. Since antibiotics are increasingly being applied as individual treatments, and anesthetics, sedatives, and injectable nonsteroidal anti-inflammatory drugs are increasingly being used for herd treatments [107], the listed product groups selected for further assessment should reflect the environmental toxicity besides their changing relevance in animal production. In some production processes such as castration, pain medication is currently applied as an individual treatment or to half of the herd (50% herd treatment), which would require the addition in Table 2. This requires monitoring the data of all VMP groups, whereby this information is already available on the individual farm level.

Animal type-related default values

Husbandry system

Table 3 shows the original VMP guideline Table 3 [22], with our proposed amendments. We suggest replacing the term “body weight” in the original VMP guideline Table 3 [22] with the term “average body weight” from Montforts [21] to enable the reader to easily understand the concept of higher values of maximum body weight and the differences therein. The average body weight is calculated over the production period [21] and is defined as the sum of the weight at housing-in (start of the production period or birth) and the weight at removal (end of the production period or slaughtering) divided by 2. The pasture-to-stable ratio is an authors’ suggestion to represent existing differences in husbandry systems not included in the housing factor. The value of pasture-to-stable ratio is 1 if animals have no access to pasture, or < 1 if animals have access to pasture.

Table 3 List of suggested amendments (black) to the original (gray or crossed out) values in the VMP guideline Table 3 [22], modified with recent data considering the N-reduced feeding strategies

Body weight

The concept of average and maximum body weight was exemplarily visualized by the growth curve of a dairy cow (Fig. 4). Figure 4 provides a theoretical explanation of the default value calculation for both weights during various periods of growth (left) and shows how trends in animal production influence these weights (right). For example, breeders’ associations confirmed that the body weights of production animals have increased in recent years, which increased the maximum body weight as well as the average body weight in many cases. On the basis of the systematically drawn approach, weights were recalculated as shown in Table 4. Following a consistent definition of the animal type “mother with offspring until weaning”, the recalculation of average body weight should be based on weaning weights instead of birth weights, as shown in pigs (Table 4).

Fig. 4
figure4

Exemplary growth curves of dairy cows. A Growth rate of cows. The initial linear daily gain is followed by a transition, ultimately reaching a plateau, where cows are fully grown, with zero growth rate and a weight that equals their final adult body weight. B Estimation of the average body weight during the linear daily gain phase. C Underestimation of the average body weight. This occurs when the transition time is included in the calculation of the average body weight. DF Changes (black) compared with the standard growth curve (gray, dashed) in animal production are mirrored as changes in the growth curve: a taller shape of the animals increases the maximum body weight (D); a higher functional longevity increases the proportion of time at fully grown (E); and a lower growth rate enhances the proportion of time at linear growth (F)

Table 4 Recalculation of the average body weight of several animal types

N-excretion

N-reduced feeding is used on an increasing number of farms in Europe, as indicated by the number of funded projects and as shown by studies on feeding strategies for reducing N [137,138,139]. The regulatory requirement to limit N entries via organic fertilizer [140] leads to several strategies for optimizing N efficiency in animal production systems and for reducing N excretion using rations with lower total N. The implementation of resource-efficient feeding strategies will continue over the next few years, which will likely result in a lower amount of produced N in the future.

Thus, we suggest calculating an average of the existing value of “nitrogen produced in one year per place” used in the EMA [22] and of recent calculations from the Chamber of Agriculture of North Rhine-Westphalia [29]. Using the average of the existing and new values might enable the continuation of the trend and reflect developments under practical conditions. As discussed above, N excretion is a result of the level of intake, defined by the N content of feed and the total amount of feed consumed, as well as metabolism. Intake is highly dependent on the performance level, i.e., the higher the production level, the higher the amount of N produced per place per year [29]. When this factor is used in the calculation of PECsoil initial for animals reared in stables (Eq. 2, [22]) as a denominator, higher performance enables higher doses of VMPs with the same threshold for PECsoil. According to recent developments in animal breeding and animal welfare, high performance is very critically discussed and sometimes associated with higher incidence of the so-called production diseases [141, 142]. This is why we recommend adopting the variable “nitrogen excretion per year and place” very carefully while keeping in mind that current high performance will likely be limited to a certain extent in the future. This leads to a lower dilution effect of the VMP as a function of PECsoil.

Default values for pasture animals

Table 5 of the original VMP guideline [22] describes the daily dung production for pasture animals. Since [22] the body weight is shown twice with only little additional information, it seems suitable to combine the two original tables into one as shown in Table 5. To enhance the understanding of the default values, it would be preferable to add the term “average body weight” to the original VMP guideline Tables 3 and 6 and the term “maximum body weight” to the original VMP guideline Tables 4 and 5 (Table 5). Additionally, a row with values for laying hens was added because laying hens are also partly kept free-range with direct entries of VMPs to the soil. Likely, daily dung production increases relative to body weight, but data are rare.

Table 5 Suggestion for updating the original VMP guideline Tables 4 and 5 [22] containing default values for pasture animals

For all newly suggested animal types, data regarding storage time and N production during storage are rare, and further research is necessary for recommending realistic default values. Since the water content of dung varies, especially when animals got treatments (e.g., diarrhea), daily dung production should have been indicated as dry matter instead of wet weight.

Effects of changes in animal husbandry on PEC calculation

Default values show a linear relationship with the result of PECsoil calculation (Eqs. 1–3, VMP guideline, [22]). This suggests the higher the value of the numerator, the higher the calculated PEC value, and vice versa. Conversely, the higher the dominator, the lower the calculated PEC value. Positive and negative correlations between the calculated PEC and default values are indicated in Table 6.

Table 6 Factors included in the PECsoil initial calculation and their relationship with the result (positive correlation, negative correlation, constant factor, and factor neglected in the respective equation), the summarized trends in animal husbandry, and the expected effect on PECsoil initial

Only a few factors will lead to an increase in the calculated PEC values after an update, as suggested above. These factors include body weight, number of daily milkings, and housing factor. As suggested, we specified consequently the default value “body weight” in either average or maximum body weight for the PECsoil calculations as in Table 6. Animal body weight varies substantially between breeds, whereas housing factor differs with the type of pasture management. To calculate body weight and housing factor, we recommend collecting reliable data on the number, breed, and representative growth curves of animals as well as their pasture management and housing systems. Generalization for all animals of the same type regardless of the production system and management as done for the housing factor, the newly suggested pasture-to-stable ratio (Table 3) or stocking density seems to be only a rough estimate (Fig. 2), but it is currently the most suitable alternative for modeling VMP entries in the environment.

Changes in animal husbandry reflect the recent effort to enhance animal health, fitness, longevity, and other animal welfare indicators, which will likely continue in the future. In synergy with many of the changes in animal husbandry, the result of the assumed updated PEC calculation may lead to lower PEC values in the future (Table 6). This is reflected by all factors included in the PEC calculation that lead to a decline of calculated PEC values after an update, as suggested (Table 6). The penetration depth of manure in soil after application must be taken into account in order to estimate how active substances contained in manure might affect the soil and its organisms. The deeper the manure is incorporated, the more likely it is for active substances to migrate into deeper layers of soil or even into groundwater. In the past, organic fertilizers were mainly applied on croplands in the depth of 20 to 30 cm with a plow, but nowadays they are applied more superficially (3–15 cm) with modern technologies. Slurry and poultry manure penetrated into soil by 3 to 8 cm, fermentation residues from biogas plants by 3 to 15 cm and manure from hoofed livestock by 8 to 15 cm [146].

Different application scenarios of VMPs, especially with low-dose VMPs, lead to the expectation that some VMPs might never exceed the threshold of 100 µg kg−1 for PECsoil initial, although the substance might be highly toxic for the environment [38]. Especially some antibiotics, such as gentamicin, tilmicosin, tulathromycin, and long-acting oxytetracycline [38], are administered at a relatively low dose but may exert high impact on the environment [154,155,156,157,158,159,160]. By revising the questions in the decision tree, it can be discussed if and how toxicity can be included in Phase I of the current ERA for VMPs.

Other potentially relevant factors during an ERA

Informal records showing the use of off-label topical antibiotics in production systems indicate that a self-mixed combination of a tyrothricin-containing human medical product and baby powder is applied prophylactically to piglets during castration [94]. In the case of some minor species and seldomly appearing diseases, rededication is necessary and is possible in Germany because of the missing VMP alternatives and the imperative to treat an animal according to the animal protection law [73, 161, 162]. The so-called off-label uses are increasingly restricted and required a valid justification and a detailed documented diagnosis. Unfortunately, only limited data are available on off-label use. If these data had been available, a systematic analysis might have identified common scenarios of off-label use. For now, only case data can be used; however, documentations from farms indicate that blind spots exist, which will not be covered during the approval of VMPs. The off-label use of topical VMPs must be investigated in more detail in future research. We recommend keeping off-label use in mind due to the risk of additional, currently neglected, environmental entries or establish a regulation of off-label use as implemented for aquaculture recently [73]. It can be discussed if the approval process, particularly Phase I, should include a question about the potential fields of off-label use to further address their environmental impact and to enable a retrospective analysis of common off-label cases.

Currently, excretion via feces and urine are included in the model used for environmental entries via manure, but N loads of waste milk are neglected [21]. Milk constitutes a substantial pathway of N excretion, as shown in table S8. Additionally, intramammary preparations are released via milk. Waste milk is recommended to be disposed into manure since feeding is prohibited and leads to an increase in antibiotic resistance [19]. Additionally, it is also necessary to address the disposal of waste water, which occurs in the pipe systems past a treatment administered orally via water, especially in poultry and pig production systems, and which should be released to make sure feed and drinking water are VMP free and to begin with withdrawel times not too early. The disposal of waste milk and waste water as well as the emission of resistance against antibiotics and anthelmintics via air or slurry represent pathways currently not included in the ERA models. It is important to further develop the existing models for addressing the exposure routes in the future in a more detailed manner.

Some animal types are often exposed to a higher risk of infection, for example, poultry kept for breeding because of higher performance for egg production and sows or cows categorized as “mothers including offspring” because of gravidity or lactation [163, 164]. These animals are treated several times with VMPs in their lifetime. Higher risk of infection results in a higher prevalence of treatments, which is likely mirrored in the spread of resistance [24]. The current ERA does not address these risks.

Perspective

Animal welfare, consumer safety, and environmental protection in animal husbandry are increasingly implemented in standards of production chains and demanded by consumers as well as policy-makers. Quantities of most VMPs, especially administered antibiotics, are predominantly declining because of regulations, higher monitoring efforts, and industry-specific standards. However, monitoring measures should be expanded to other groups of VMPs (e.g., antiparasitics, hormones, and pain medications) and include different usages (e.g., drying-off and mastitis treatments in dairy cows, and mastitis, metritis, and agalactia treatment in sows). This will enable a more reliable estimation of the proportion of herd treatments. Monitoring will provide incentives to further improve animal health and reduce environmental entries in general.

Further harmonization of the farm animal categorization and time schedule for recording of animal numbers in the EU would considerably simplify the empirical data on livestock populations across the EU, which would enable us to compare statistics and make valid statements. Another challenge highlighted in the present study is the lack of data, particularly in the field of free-range husbandry. Valid data are urgently needed to be able to make more detailed statements about uncontrolled excretions in free-range husbandry scenarios and the associated environmental exposure. Generally, more information about husbandry systems and animal numbers is needed not only for modeling ERA of VMPs, but also for monitoring epizootic or zoonotic diseases (Haupt et al., unpublished manuscript).

The collected data can provide a basis for updating the VMP guideline tables. The basis of this research was German data. To update the default values and to draw more general conclusions, information from other EU member states will need to be considered. Besides the discussion of default values, a validation of the exposure model is recommended to ensure that the results of the models are generally protective and do not underestimate the concentration of VMPs in the environment. Updating the default values will also help to avoid possible overestimates, which would lead to constant discussion about the default values, calculations or ERA results in case of rejected VMPs. Nevertheless, it will be challenging to include possible relevant exposure routes in the models in the future, e.g., for insects used as food- and feed-producing species. This may reduce the acceptance of environmental risks because of the lack of models for the unique way of exposure, e.g., isoflurane entries via air, or the retroactive reevaluation of existing authorizations with all the difficulties.

To accurately determine the suggested new factor for access to pasture (pasture-to-stable ratio; Table 3), more data on housing conditions are needed from all European countries.

Environmental risks can be substantially reduced if good agricultural practice is applied. For example, pasture care by harrowing the dropped dung prevents local peak entries. Further implementation of good scientific practice requires research, which will facilitate the development of recommendations and the transfer of scientific knowledge.

In conclusion, the model of the ERA of VMPs in the EU is still important and suitable for the intended purpose. However, due to changes in livestock husbandry, an update for the ERA is required. It seems to be possible to reduce the questions of Phase I assessment and revise the default values and relevant factors to mirror recent changes. Certain areas of the ERA need to be revised as they are currently too vague. It would be useful to make these areas more specific. One approach could be to reduce the number of questions in the decision tree and to adapt the default values to current changes. Considering the One Health aspect, farmers, veterinarians and environmental scientists should be involved in a revision of the model.

Availability of data and materials

The datasets and records used in the present study are available from the corresponding author upon reasonable request.

Abbreviations

EIA:

Environmental impact assessment

EMA:

European Medicine Agency

ERA:

Environmental risk assessment

EU:

European Union

PEC:

Predicted environmental concentration

RMM:

Risk mitigation measure

VICH:

Veterinary International Conference on Harmonization VMPs: Veterinary medicinal products

References

  1. 1.

    Maynard MS, Wislocki PG, Ku CC (1989) Fate of avermectin B1a in lactating goats. J Agric Food Chem 37:1491–1497. https://doi.org/10.1021/jf00090a008

    CAS  Article  Google Scholar 

  2. 2.

    Kemper N (2008) Veterinary antibiotics in the aquatic and terrestrial environment. Ecol Ind 8:1–13. https://doi.org/10.1016/j.ecolind.2007.06.002

    CAS  Article  Google Scholar 

  3. 3.

    Boxall ABA (2010) Veterinary medicines and the environment. In: Cunningham F, Elliott J, Lees P (eds) Comparative and veterinary pharmacology. Handbook of experimental pharmacology, 291–314. https://doi.org/10.1007/978-3-642-10324-7_12

  4. 4.

    Wallmann J, Bode C, Köper L, Heberer T (2020) Abgabemengenerfassung von Antibiotika in Deutschland 2019:1102–1109

  5. 5.

    Vidaurre R, Lukat E, Steinhoff-Wagner J, Ilg Y, Petersen B, Hannappel S, Möller K (2016) Konzepte zur Minderung von Arzneimitteleinträgen aus der landwirtschaftlichen Tierhaltung in die Umwelt. https://www.umweltbundesamt.de/sites/default/files/medien/2546/publikationen/fachbroschuere_tam_final.pdf. Accessed 10 Nov 2020

  6. 6.

    Bundesministerium für Ernährung und Landwirtschaft BMEL (2018) AG Antibiotikaresistenz Lagebild zur Antibiotikaresistenz im Bereich Tierhaltung und Lebensmittelkette

  7. 7.

    Lützhøft HH, Halling-Sørensen B, Jørgensen SE (1999) Algal toxicity of antibacterial agents applied in Danish fish farming. Arch Environ Contam Toxicol 36:1–6. https://doi.org/10.1007/s002449900435

    Article  Google Scholar 

  8. 8.

    Boxal ABA, Fogg LA, Blackwell PA, Kay P, Pemberton EJ, Croxford A (2004) Veterinary medicines in the environment. Rev Environ Contam Toxicol 1–91. https://doi.org/10.1007/0-387-21729-0_1

  9. 9.

    Liebig M, Fernandez AA, Blübaum-Gronau E, Boxall ABA, Brinke M, Carbonell G, Egeler P, Duis K (2010) Environmental risk assessment of ivermectin: a case study. Integr Environ Assess 6(Suppl):567–587. https://doi.org/10.1002/ieam.96

    CAS  Article  Google Scholar 

  10. 10.

    Ebert I, Bachmann J, Kühnen U, Küster A, Kussatz C, Maletzki D, Schlüter C (2011) Toxicity of the fluoroquinolone antibiotics enrofloxacin and ciprofloxacin to photoautotrophic aquatic organisms. Environ Toxicol Chem 30:2786–2792. https://doi.org/10.1002/etc.678

    CAS  Article  Google Scholar 

  11. 11.

    González-Pleiter M, Gonzalo S, Rodea-Palomares I, Leganés F, Rosal R, Boltes K, Marco E, Fernández-Pinas F (2013) Toxicity of five antibiotics and their mixtures towards photosynthetic aquatic organisms: implications for environmental risk assessment. Water Res 47:2050–2064. https://doi.org/10.1016/j.watres.2013.01.020

    CAS  Article  Google Scholar 

  12. 12.

    Umweltbundesamt UBA (German Environment Agency (2018)) Umweltwirkungen von Tierarzneimitteln. https://www.umweltbundesamt.de/umweltwirkungen-von-tierarzneimitteln. Accessed 5 Aug 2020

  13. 13.

    Du L, Liu W (2012) Occurrence, fate, and ecotoxicity of antibiotics in agro-ecosystems. A review. Agron Sustain Dev 32:309–327. https://doi.org/10.1007/s13593-011-0062-9

    CAS  Article  Google Scholar 

  14. 14.

    Zhou X, Qiao M, Wang F-H et al (2017) Use of commercial organic fertilizer increases the abundance of antibiotic resistance genes and antibiotics in soil. Environ Sci Pollut Resolut 24:701–710. https://doi.org/10.1007/s11356-016-7854-z

    CAS  Article  Google Scholar 

  15. 15.

    Hamscher G, Mohring SAI (2012) Tierarzneimittel in Böden und in der aquatischen Umwelt. Chem Ing Tech 84:1052–1061. https://doi.org/10.1002/cite.201100255

    CAS  Article  Google Scholar 

  16. 16.

    Carballo M, Aguayo S, González M et al (2016) Environmental assessment of tetracycline’s residues detected in pig slurry and poultry manure. JEP 07:82–92. https://doi.org/10.4236/jep.2016.71008

    CAS  Article  Google Scholar 

  17. 17.

    Guo T, Lou C, Zhai W, Tang X, Hashmi MZ, Murtaza R, Li Y, Liu X, Xu J (2018) Increased occurrence of heavy metals, antibiotics and resistance genes in surface soil after long-term application of manure. Sci Total Environ 635:995–1003. https://doi.org/10.1016/j.scitotenv.2018.04.194

    CAS  Article  Google Scholar 

  18. 18.

    Cycoń M, Mrozik A, Piotrowska-Seget Z (2019) Antibiotics in the soil environment-degradation and their impact on microbial activity and diversity. Front Microbiol 10:338. https://doi.org/10.3389/fmicb.2019.00338

    Article  Google Scholar 

  19. 19.

    European Agency for the Evaluation of Medicinal Products EMEA (2000) Note for Guidance for the Determination of Withdrawal Periods for Milk. EMEA/CVMP/473/98-FINAL. https://www.ema.europa.eu/en/documents/scientific-guideline/note-guidance-determination-withdrawal-periods-milk_en.pdf. Accessed 12 Dec 2020

  20. 20.

    European Medicines Agency (2006) CVMP guideline on fixed combination products (EMEA/CVMP/83804/2005). https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-pharmaceutical-fixed-combination-products_en.pdf. Accessed 14 Sep 2020

  21. 21.

    Montforts MHMM (2003) Environmental risk assessment for veterinary medicinal products Part 1, Non immunological drug substances. Second update. RIVM report 320202001/200. National Institute of Public Health and the Environment Bilthoven, the Netherlands. https://www.rivm.nl/bibliotheek/rapporten/320202001.pdf. Accessed 14 Sep 2020

  22. 22.

    European Medicines Agency (2016) Guideline on environmental impact assessment for veterinary medicinal products in support of the VICH guidelines GL6 and GL38: EMA/CVMP/ERA/418282/2005-Rev.1-Corr. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-environmental-impact-assessment-veterinary-medicinal-products-support-vich-guidelines-gl6_en.pdf. Accessed 14 Sep 2020

  23. 23.

    Koschorreck J, Koch C, Rönnefahrt I (2002) Environmental risk assessment of veterinary medicinal products in the EU—a regulatory perspective. Toxicol Lett 131:117–124

    CAS  Article  Google Scholar 

  24. 24.

    Heinemann C, Leubner C, Savin M, Sib E, Schmithausen R, Bierbaum G, Petersen B, Steinhoff-Wagner J (2019) Vorkommen antibiotikaresistenter Keime in Hähnchenmastbetrieben unterschiedlicher Haltungsform: Paper presented at BTU conference, Bonn, Germany, 24–26 September 2019

  25. 25.

    Bundesamt für Verbraucherschutz und Lebensmittelsicherheit BVL (2020) Bekanntmachung des Medians und des dritten Quartils der vom 1. Juli 2019 bis 31. Dezember 2019 erfassten bundesweiten betrieblichen Therapiehäufigkeiten für Mastrinder, Mastschweine, Masthühner und Mastputen nach § 58c Absatz 4 des Arzneimittelgesetzes vom 17. März 2020. https://www.bvl.bund.de/SharedDocs/Downloads/05_Tierarzneimittel/Bekanntmachungen/2020_03_31_Bekanntmachung_BAnz.pdf?__blob=publicationFile&v=2-. Accessed 15 Oct 2020

  26. 26.

    Tierschutz-Nutztierhaltungsverordnung Tierschutz-Nutztierhaltungsverordnung (TierSchNutztV) in der Fassung der Bekanntmachung vom 22. August 2006 (BGBl. I S. 2043), die zuletzt durch Artikel 3 Absatz 2 des Gesetzes vom 30. Juni 2017 (BGBl. I S. 2147) geändert worden ist. (Animal Protection Keeping of Production Animals Order). https://www.gesetze-im-internet.de/tierschnutztv/TierSchNutztV.pdf. Accessed 14 Sep 2020

  27. 27.

    Bundesanstalt für Landwirtschaft und Ernährung BLE (2019) Jungebermast als Alternative zur Mast von Kastraten. https://www.praxis-agrar.de/tier/schweine/alternativen-zur-betaeubungslosen-ferkelkastration/jungebermast/basisartikel-jungebermast/. Accessed 15 Oct 2020

  28. 28.

    Interessengemeinschaft der Schweinehalter Deutschland e.V. ISN e.V. (2019) Kastration spezial. Länderreport—Ein Blick über die Grenzen. Interessengemeinschaft der Schweinehalter Deutschland e.V. ISN e.V. (Interest group of pig farmer in Germany) (2019) Kastration spezial. Länderreport—Ein Blick über die Grenzen

  29. 29.

    Landwirtschaftskammer Nordrhein-Westfalen LKW NRW (2020) Excel-Anwendung Nährstoffbeurteilungsblatt NRW 2020. Münster (Germany): Landwirtschaftskammer Nordrhein-Westfalen. https://www.landwirtschaftskammer.de/landwirtschaft/ackerbau/duengung/programme/nvplan/index.htm. Accessed 14 Sep 2020

  30. 30.

    Bonneau M, Weiler U (2019) Pros and cons of alternatives to piglet castration: welfare, boar taint, and other meat quality traits. Animals. https://doi.org/10.3390/ani9110884

    Article  Google Scholar 

  31. 31.

    Eurostat Organic livestock from 2012 onwards. Layinghens. https://appsso.eurostat.ec.europa.eu/nui/submitViewTableAction.do. Accessed 13 Nov 2020

  32. 32.

    Augère-Granier ML (2019) EPRS Wissenschaftlicher Dienst des Europäischen Parlaments. Der Eier- und Geflügelfleischsektor der EU. Hauptmerkmale, Herausforderungen und Perspektiven. https://www.europarl.europa.eu/RegData/etudes/IDAN/2019/644195/EPRS_IDA(2019)644195_DE.pdf. Accessed 29 Oct 2020

  33. 33.

    Bundesanstalt für Landwirtschaft und Ernährung BLE (2019) Bericht zur Markt und Versorgungslage Eier 2019. https://www.ble.de/SharedDocs/Downloads/DE/BZL/Daten-Berichte/Eier/2019BerichtEier.pdf?__blob=publicationFile&v=2. Accessed 14 Sep 2020

  34. 34.

    Statistisches Bundesamt destatis Pressemitteilung Nr. 043 vom 07. February 2019. https://www.destatis.de/DE/Presse/Pressemitteilungen/2019/02/PD19_043_413.html. Accessed 31 Jul 2020

  35. 35.

    Fleischatlas (2018) Daten und Fakten über Tiere als Nahrungsmittel. 2. Auflage. Heinrich Böll Stiftung, Berlin, Germany. https://www.bund.net/fileadmin/user_upload_bund/publikationen/massentierhaltung/massentierhaltung_fleischatlas_2018.pdf. Accessed 04 Nov 2020

  36. 36.

    Hirata M, Higashiyama M, Hasegawa N (2011) Diurnal pattern of excretion in grazing cattle. Livest Sci 142:23–32

    Article  Google Scholar 

  37. 37.

    Betteridge K, Costall D, Balladur S, Upsdell M, Umemura K (2010) Urine distribution and grazing behaviour of female sheep and cattle grazing a steep New Zealand hill pasture. Anim Prod Sci 50:624. https://doi.org/10.1071/AN09201

    Article  Google Scholar 

  38. 38.

    Lammers M (2008) Environmental Risk Assessment. Part of the overall Risk / Benefit Assessment of veterinary medicinal products. Master’s thesis. Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany

  39. 39.

    Grave K (2011) Usage in animals. Therapeutic usage of veterinary antimicrobial agents. Norm-Vet 2011. https://unn.no/Documents/Kompetansetjenester,%20-sentre%20og%20fagr%C3%A5d/NORM%20-%20Norsk%20overv%C3%A5kingssystem%20for%20antibiotikaresistens%20hos%20mikrober/Rapporter/NORM%20NORM-VET%202011.pdf#page=15. Accessed 14 Nov 2020

  40. 40.

    Hester RE, Harrison RM (2015) Pharmaceuticals in the environment. Issues in environmental science and technology 41. Royal Society of Chemistry, Cambridge

  41. 41.

    Teerlink J, Hernandez J, Budd R (2017) Fipronil washoff to municipal wastewater from dogs treated with spot-on products. Sci Total Environ 599–600:960–966. https://doi.org/10.1016/j.scitotenv.2017.04.219

    CAS  Article  Google Scholar 

  42. 42.

    Perkins R, Whitehead M, Civil W, Goulson D (2020) Potential role of veterinary flea products in widespread pesticide contamination of English rivers. Sci Total Environ. https://doi.org/10.1016/j.scitotenv.2020.143560Get

    Article  Google Scholar 

  43. 43.

    Malher X, Seegers H, Beaudeau F (2001) Culling and mortality in large dairy goat herds managed under intensive conditions in western farms. Animals C71:75–86

    Google Scholar 

  44. 44.

    Escareño L, Salinas-Gonalez H, Wurzinger M, Iñiguez L, Sölkner J, Meza-Herrera C (2012) Dairy goat production systems. Trop Anim Health Prod. https://doi.org/10.1007/s11250-012-0246-6

    Article  Google Scholar 

  45. 45.

    Grosso L, Battini M, Wemelsfelder F, Barbieri S, Minero M, Dalla Costa E, Mattiello S (2016) On-farm qualitative behaviour assessment of dairy goats in different housing conditions. Appl Anim Behav Sci 180:51–57

    Article  Google Scholar 

  46. 46.

    Pollot GEGE (2004) Reproductive performance and milk production of Assaf sheep in an intensive management system. J Dairy Sci 87:3690–3703. https://doi.org/10.3168/jds.S0022-0302(04)73508-0

    Article  Google Scholar 

  47. 47.

    Caroprese M (2008) Sheep housing and welfare. Small Rumin Res 76:21–25. https://doi.org/10.1016/j.smallrumres.2007.12.015

    Article  Google Scholar 

  48. 48.

    Pulina G, Milan MJ, Lavin MP, Theodoridis A, Morin E, Capotel J, Thomas DL, Francesconi AHD, Caja G (2018) Invited review: current production trends, farm structures, and economics of the dairy sheep and goat sectors. J Dairy Sci. https://doi.org/10.3168/jds.2017-14015

    Article  Google Scholar 

  49. 49.

    Statistisches Bundesamt destatis (2010) Reihe 3. Heft 6. Landwirtschaft, Forstwirtschaft und Fischerei. Düngemittel, Unterbringung von Tieren in Innenräumen, Weidehaltung. Betriebsstrukturerhebung 2010. https://www.destatis.de/DE/Themen/Branchen-Unternehmen/Landwirtschaft-Forstwirtschaft-Fischerei/Produktionsmethoden/Publikationen/Downloads-Produktionsmethoden/stallhaltung-weidehaltung-2032806109004.html. Accessed 06 Feb 2020

  50. 50.

    Mueller Ab (2020) Aus Mist Geld machen. Die Vorzüge der schwarzen Soldatenfliege. Hamburg (Germany): DER SPIEGEL (online). https://www.spiegel.de/panorama/aus-mist-geld-machen-die-vorzuege-der-schwarzen-soldatenfliege-a-3a93e0fb-2510-4338-835e-7bb66fe44ccb. Accessed 05 Nov 2020

  51. 51.

    Moula N, Scippo M-L, Douny C et al (2018) Performances of local poultry breed fed black soldier fly larvae reared on horse manure. Anim Nutr 4:73–78. https://doi.org/10.1016/j.aninu.2017.10.002

    Article  Google Scholar 

  52. 52.

    Adámková A, Adámek M, Mlček J et al (2017) Welfare of the mealworm (Tenebrio molitor) breeding with regard to nutrition value and food safety. Potravinarstvo. https://doi.org/10.5219/779

    Article  Google Scholar 

  53. 53.

    Flachowsky G, Südekum KH, Meyer U (2019) Protein tierischer Herkunft: Gibt es Alternativen? Züchtungskunde 91(3):178–213

    Google Scholar 

  54. 54.

    Statistisches Bundesamt destatis (2016) Reihe 3. Ausgabe 2.2.1. Landwirtschaft, Fischerei. Biologische Bauernhöfe. Betriebsstrukturerhebung 2016. file:///C:/Users/Lenovo/Downloads/oekologischer-landbau-2030221169004.pdf. Accessed 06 Feb 2020

  55. 55.

    Bundesanstalt für Landwirtschaft und Ernährung BLE (2019) Bericht zur Markt- und Versorgungslage Fleisch 2019. https://www.ble.de/SharedDocs/Downloads/DE/BZL/Daten-Berichte/Fleisch/2019BerichtFleisch.pdf?__blob=publicationFile&v=2. Accessed 14 Sep 2020

  56. 56.

    Bundesministerium für Ernährung und Landwirtschaft BMEL (2019) Bienen; 2019. https://www.bmel.de/DE/Tier/Nutztierhaltung/Bienen/bienen_node.html/. Accessed 06 Feb 2020

  57. 57.

    Bundesministerium für Ernährung und Landwirtschaft BMEL (2019) Deutschland wie es isst. Der Ernährungsreport 2019. https://www.bmel.de/SharedDocs/Downloads/Broschueren/Ernaehrungsreport2019.pdf?__blob=publicationFile /. Accessed 14 Sep 2020

  58. 58.

    Bilotta GS, Brazier RE, Haygarth PM (2007) The impacts of grazing animals on the quality of soils, vegetation, and surface waters in intensively managed grasslands. Adv Agron 94:237–280

    CAS  Article  Google Scholar 

  59. 59.

    Regulation (EC) No 1107/2009 of the European Parliament and of the council of 21 October 2009 concerning the placing of plant protection products on the market and repealing Council Directives 79/117/EEC and 91/414/EEC. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32009R1107&from=EN. Accessed 30 Oct 2020

  60. 60.

    European Food Safety Authority (2015) Guidance Document for predicting environmental concentrations of active substances of plant protection products and transformation products of these active substances in soil. EFSA J 15:e04982. https://doi.org/10.2903/j.efsa.2017.4982

    Article  Google Scholar 

  61. 61.

    Eurostat Bovine population, annual data. https://ec.europa.eu/eurostat/databrowser/view/apro_mt_lscatl/default/table?lang=en. Accessed 30 Oct 2020

  62. 62.

    Eurostat (2020) Cattle: number of farms and heads and fodder crops by agricultural size of farms and size of cattle herd. https://appsso.eurostat.ec.europa.eu/nui/show.do?dataset=ef_lscatl&lang=en. Accessed 30 Oct 2020

  63. 63.

    Eurostat Geflügel: Anzahl der Betriebe und Anzahl von Geflügel nach wirtschaftlicher Betriebsgröße und Zahl der Masthähnchen. http://appsso.eurostat.ec.europa.eu/nui/show.do?dataset=ef_lsbroiecs&lang=de. Accessed 30 Oct 2020

  64. 64.

    Eurostat (2020) Pigs: number of farms and heads by agricultural size of farm (UAA) and size of pig herd. https://ec.europa.eu/eurostat/databrowser/view/ef_lspigaa/default/table?lang=en. Accessed 30 Oct 2020

  65. 65.

    Eurostat Pig population, annual data. https://appsso.eurostat.ec.europa.eu/nui/show.do?dataset=apro_mt_lspig&lang=en. Accessed 30 Oct 2020

  66. 66.

    Eurostat (2020) Poultry by nuts 2 regions. https://ec.europa.eu/eurostat/web/products-datasets/-/ef_lsk_poultry. Accessed 30 Oct 2020

  67. 67.

    Eurostat (2020) Schafe: Anzahl der Betriebe, Anzahl der Schafe und Flächen mit Futterpflanzen nach landwirtschaftlicher Fläche und Anzahl der Schafe. https://appsso.eurostat.ec.europa.eu/nui/show.do?dataset=ef_lssheep&lang=de. Accessed 30 Oct 2020

  68. 68.

    Eurostat (2020) Schafbestand, jährliche Daten. http://appsso.eurostat.ec.europa.eu/nui/show.do?dataset=apro_mt_lssheep&lang=de. Accessed 30 Oct 2020

  69. 69.

    Eurostat Ziegen: Anzahl der Betriebe, Anzahl der Ziegen und Flächen mit Futterpflanzen nach landwirtschaftlicher Fläche und Anzahl der Ziegen. https://appsso.eurostat.ec.europa.eu/nui/show.do?dataset=ef_lsgoat&lang=de. Accessed 30 Oct 2020

  70. 70.

    Eurostat (2020) Ziegenbestand, jährliche Daten. https://appsso.eurostat.ec.europa.eu/nui/show.do?dataset=apro_mt_lsgoat&lang=en. Accessed 30 Oct 2020

  71. 71.

    Vuorisola S Number of livestock in spring of 2013. https://stat.luke.fi/en/number-livestock-spring-2013_en. Accessed 04 Nov 2020

  72. 72.

    Charlier J, Morgan ER, Rinaldi L, van Dijk J, Demeler J, Höglund J, Hertzberg H, van Ranst B, Hendrickx G, Vercruysse J, Kenyon F (2014) Practices to optimise gastrointestinal nematode control on sheep, goat and cattle farms in Europe using targeted (selective) treatments. Vet Rec 175:250–255. https://doi.org/10.1136/vr.102512

    CAS  Article  Google Scholar 

  73. 73.

    Regulation (EU) 2019/6 of the European Parliament and of the council of 11 December 2018 on veterinary medicinal products and repealing Directive 2001/82/EC. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32019R0006&from=EN. Accessed 30 Oct 2020

  74. 74.

    European Food Safety Authority (2018) Report for 2016 on the results from the monitoring of veterinary medicinal product residues and other substances in live animals and animal products. EFSA supporting publication 2018:EN-1358. 75 pp. https://doi.org/10.2903/sp.efsa.2018.EN-1358

  75. 75.

    European Food Safety Authority (2020) Report for 2018 on the results from the monitoring of veterinary medicinal product residues and other substances in live animals and animal products. EFSA supporting publication 2020:EN-1775. 74 pp. https://doi.org/10.2903/sp.efsa.2020.EN-1775

  76. 76.

    Hofacre CL, Fricke JA, Inglis T (2013) Antimicrobial drug use in poultry. In: Antimicrobial therapy in veterinary medicine, 5th edn. Wiley, New Jersey

  77. 77.

    Trauffler M, Griesbacher A, Fuchs K, Köfer J (2014) Antimicrobial drug use in Austrian pig farms: plausibility check of electronic on-farm records and estimation of consumption. Vet Rec. https://doi.org/10.1136/vr.102520

    Article  Google Scholar 

  78. 78.

    Sjölund M, Backhans A, Greko C, Emanuelson U, Lindberg A (2015) Antimicrobial usage in 60 Swedish farrow-to-finish pig herds. Prev Vet Med. https://doi.org/10.1016/j.prevetmed.2015.07.005

    Article  Google Scholar 

  79. 79.

    Vandael F, Filippitzi ME, Dewulf J, Daeseleire E, Eeckhout M, Devreese M, Croubels S (2019) Oral group medication in pig production: characterising medicated feed and drinking water systems. Vet Rec. https://doi.org/10.1136/vetrec-2019-105495

    Article  Google Scholar 

  80. 80.

    Crispie F, Flynn J, Ross RP, Hill C, Meaney W (2004) Dry cow therapy with a non-antibiotic intramammary teat seal—a review. Ir Vet J. https://doi.org/10.1186/2046-0481-57-7-412

    Article  Google Scholar 

  81. 81.

    McDougall S, Parker KI, Heuer C, Compton CWR (2009) A review of prevention and control of heifer mastitis via non-antibiotic strategies. Vet Microbiol. https://doi.org/10.1016/j.vetmic.2008.09.026

    Article  Google Scholar 

  82. 82.

    Krömker V, Leimbach S (2017) Mastitis treatment—reduction in antibiotic usage in dairy cows. Reprod Domest Anim. https://doi.org/10.1111/rda.13032

    Article  Google Scholar 

  83. 83.

    Biscarini F, Cremonesi P, Castiglioni B, Stella A, Bronzo V, Locatelli C, Moroni P (2020) A randomized controlled trial of teat-sealant and antibiotic dry-cow treatments for mastitis prevention shows similar effect on the healthy milk microbiome. Front Vet Sci. https://doi.org/10.3389/fvets.2020.00581

    Article  Google Scholar 

  84. 84.

    Martin L, Sauerwein H, Büscher W, Müller U (2020) Automated gradual reduction of milk yield before dry-off: effects on udder health, involution and inner teat morphology. Livest Sci. https://doi.org/10.1016/j.livsci.2020.103942

    Article  Google Scholar 

  85. 85.

    Giffhorn E, Hemme T (2002) Milchquotenausstieg 2008: eine Analyse am Beispiel typischer Betriebe in den neuen Ländern. Arbeitsbericht Bundesforschungsanstalt für Landwirtschaft (FAL), Institut für Betriebswirtschaft, Agrarstruktur und Ländliche Räume, No. 06/2002. http://hdl.handle.net/10419/39379. Accessed 14 Sep 2020

  86. 86.

    Tergast H, Schickramm L, Lindena T, Ellßel, R, Hansen H (2018) Steckbriefe zur Tierhaltung in Deutschland: Milchkühe. https://literatur.thuenen.de/digbib_extern/dn061460.pdf. Accessed 14 Aug 2020

  87. 87.

    Agriculture and Horticulture Development Board AHDB (2019) Dairy performance results 2017/2018. https://projectblue.blob.core.windows.net/media/Default/Dairy/Publications/DairyPerformanceResults1960_190412_WEB.pdf. Accessed 29 Jul 2020

  88. 88.

    Speksnijder DC, Mevius DJ, Bruschke CJM, Wagenaar JA (2014) Reduction of veterinary antimicrobial use in the Netherlands. The Dutch Success Model. Zoonoses Public Health 62:79–87. https://doi.org/10.1111/zph.12167

    Article  Google Scholar 

  89. 89.

    Sitkowska B, Piwczynski D, Aerts J, Wskowicz M (2015) Changes in milking parameters with robotic milking. Arch Tierz 58:137

    Google Scholar 

  90. 90.

    Duncan JS, Angell JW, Carter SD, Evans NJ, Sullivan LE, Grove-White DH (2014) Contagious ovine digital dermatitis: an emerging disease. Vet J. https://doi.org/10.1016/j.tvjl.2014.06.007

    Article  Google Scholar 

  91. 91.

    Han S, Mansfield KG (2014) Severe hoof disease in free-ranging Roosevelt Elk (Cervus elaphus roosevelti) in southwestern Washington, USA. J Wildl Dis 50:259–270. https://doi.org/10.7589/2013-07-163

    Article  Google Scholar 

  92. 92.

    Sullivan LE, Evans NJ, Blowey RW, Grove-White DH, Clegg SR, Duncan JS, Carter SD (2015) A molecular epidemiology of treponemes in beef cattle digital dermatitis lesions and comparative analyses with sheep contagious ovine digital dermatitis and dairy cattle digital dermatitis lesions. Vet Microbiol. https://doi.org/10.1016/j.vetmic.2015.04.011

    Article  Google Scholar 

  93. 93.

    Wilson-Welder JH, Alt DP, Nally JE (2015) Digital dermatitis in cattle: current bacterial and immunological findings. Animals. https://doi.org/10.3390/ani5040400

    Article  Google Scholar 

  94. 94.

    Schmid SM, Leubner CD, Köster LN, Steinhoff-Wagner J (2020) Status quo-Erhebung zum betriebsindividuellen Management der Kastration von Saugferkeln in Deutschland. Züchtungskunde 2020:355–372

  95. 95.

    Strobel M HPA (2012) The effect of topical anti-infective application at castration and tail docking of baby pigs versus doing nothing. AASV annual meeting: integrating science, welfare, and economics in practice. https://www.aasv.org/library/swineinfo/item.php?13220. Accessed 29 Jul 2020

  96. 96.

    Arece-García J, López-Leyva Y, González-Garduño R, Torres-Hernández G, Rojo-Rubio R, Marie-Magdeleine C (2016) Effect of selective anthelmintic treatments on health and production parameters in Pelibuey ewes during lactation. Trop Anim Health Prod 48(2):283–287

    Article  Google Scholar 

  97. 97.

    Koutny H, Joachim A, Tichy A, Baumgartner W (2012) Bovine Eimeria species in Austria. Parasitol Res 110(5):1893–1901

    CAS  Article  Google Scholar 

  98. 98.

    Stromberg BEGLC (2006) Gastrointestinal nematode control programs with an emphasis on cattle. Vet Clin N Am Food Anim Pract 22(3):543–565. https://doi.org/10.1016/j.cvfa.2006.08.003

    Article  Google Scholar 

  99. 99.

    Bonsaglia EC, Gomes MS, Canisso IF, Zhou Z, Lima SF, Rall VL, Lima FS, Bonsaglia ECR, Gomes MS et al (2017) Milk microbiome and bacterial load following dry cow therapy without antibiotics in dairy cows with healthy mammary gland. Sci Rep-UK 7(1):1-10 // Milk microbiome and bacterial load following dry cow therapy without antibiotics in dairy cows with healthy mammary gland. Sci Rep 7:8067. https://doi.org/10.1038/s41598-017-08790-5

    CAS  Article  Google Scholar 

  100. 100.

    Berry EAHJE (2002) The effect of selective dry cow treatment on new intramammary infections. J Dairy Sci 85(1):112–121

    CAS  Article  Google Scholar 

  101. 101.

    Scherpenzeel CGM, Den Uijl IEM, Van Schaik G, Olde Riekerink RGM, Hogeveen H, Lam TJGM (2016) Effect of different scenarios for selective dry-cow therapy on udder health, antimicrobial usage, and economics. J Dairy Sci 99(5):3753–3764. https://doi.org/10.3168/jds.2015-9963

    CAS  Article  Google Scholar 

  102. 102.

    Holyoake PK, Collins A, Donahoo M, Lising R, Emery D, Holyoake PK, Collins A et al (2009) Identifying obstacles to reducing the use of antibiotics to control porcine proliferative enteropathy. Aust Vet J 87 (1–2):33–34 // Identifying obstacles to reducing the use of antibiotics to control porcine proliferative enteropathy. Aust Vet J 87:33–34. https://doi.org/10.1111/j.1751-0813.2008.00372.x

    CAS  Article  Google Scholar 

  103. 103.

    Williams O, Clark I, Gomes RL, Perehinec T, Hobman JL, Stekel DJ, Lester E, Williams O, Clark I et al (2019) Removal of copper from cattle footbath wastewater with layered double hydroxide adsorbents as a route to antimicrobial resistance mitigation on dairy farms. Sci Total Environ 655:1139–1149. https://doi.org/10.1016/j.scitotenv.2018.11.330

    CAS  Article  Google Scholar 

  104. 104.

    Zingg D, Steinbach S, Kuhlgatz C, Rediger M, Schüpbach-Regula G, Aepli M, Groneng GM, Dürr S, Zingg D, Steinbach S et al (2017) Epidemiological and economic evaluation of alternative on-farm management scenarios for ovine footrot in Switzerland. Front Vet Sci 4:70. https://doi.org/10.3389/fvets.2017.00070

    Article  Google Scholar 

  105. 105.

    Yeshimebet CBA, Chanyalew Y, Gemeda B (2014) Comparative evaluation of traditional herb and conventional treatment of ovine foot rot in Ethiopia. Int J Livest Res 4:42–51. https://doi.org/10.5455/ijlr.20140109084439

    Article  Google Scholar 

  106. 106.

    Faulkner PM, Weary DM (2000) Reducing pain after dehorning in dairy calves. J Dairy Sci 83:2037–2041

    CAS  Article  Google Scholar 

  107. 107.

    Ballou MA, Sutherland MA, Brooks TA, Hulbert LE, Davis LE, Cobb CJ (2013) Administration of anesthetic and analgesic prevent the suppression of many leukocyte responses following surgical castration and physical dehorning. Vet Immunol Immunopathol 151(3–4):285–293. https://doi.org/10.1016/j.vetimm.2012.11.018

    CAS  Article  Google Scholar 

  108. 108.

    Kemp B, Den Hartog LA, Grooten HJG (1989) The effect of feeding level on semen quantity and quality of breeding boars. Anim Reprod Sci 20(4):245–254

    Article  Google Scholar 

  109. 109.

    Wilson ME, Rozeboom KJ, Crenshaw TD (2004) Boar nutrition for optimum sperm production. Adv Pork Prod 15:295–306

    Google Scholar 

  110. 110.

    Sulabo RC, Quackenbush J, Goodband RD, Tokach MD, DeRouchey JM, Nelssen JL, Dritz SS (2006) Predicting growth rates of adult working boars in a commercial boar stud. Kansas Agric Exp Res Rep. https://doi.org/10.4148/2378-5977.6957

    Article  Google Scholar 

  111. 111.

    Matthes W, Uetrecht D, Müller A, Delfs H, Büsing K, Claus H, Krüger K, Müller S (2014) Wirtschaftlichkeit der Ebermast. Proceedings, KTBL-Tagung „Ebermast—Stand und Perspektiven, Hannover Germany, July 2-3, 2014, KTBL Schrift 504, pp 42–52

  112. 112.

    Barth K, Braunreiter C, Fasel M, Heckendorn F, Horvat E, Jaudas U, Reinmuth B (2013) Milchziegenhaltung im Biobetrieb. https://www.naturland.de/images/Erzeuger/Betriebszweige/Schaf_Ziege/1512-milchziegenhaltung.pdf. Accessed 12 Oct 2020

  113. 113.

    Liesegang A, Risteli J, Wanner M (2007) Bone metabolism of milk goats and sheep during second pregnancy and lactation in comparison to first lactation. J Anim Physiol Anim Nutr (Berl) 91:217–225. https://doi.org/10.1111/j.1439-0396.2007.00695.x

    CAS  Article  Google Scholar 

  114. 114.

    Chamber of Agriculture of Lower Saxony (2019) Mittlere Nährstoffausscheidung und Dunganfall landwirtschaftlicher Nutztiere je belegtem Stallplatz und Jahr (gem. DüV vom 25.05.2017, Anhang 1, Tabelle 1 und Anlage 9, Tabelle 1)

  115. 115.

    Perotto D, Cue RI, Lee AJ (1992) Comparison of nonlinear functions for describing the growth curve of three genotypes of dairy cattle. Can J Anim Sci 72(4):773–782

    Article  Google Scholar 

  116. 116.

    Maltz E, Devir S, Metz JHM, Hogeveen H (1997) The body weight of the dairy cow I. Introductory study into body weight changes in dairy cows as a management aid. Livest Prod Sci 48(3):175–186

    Article  Google Scholar 

  117. 117.

    Von Davier Z, Schütte J, Efken J (2020) Steckbriefe zur Tierhaltung in Deutschland: Mastrinder. https://www.thuenen.de/de/thema/nutztiershyhaltung-und-aquakultur/haltungsverfahren-in-deutschland/konventionelle-rindermast/. Accessed 04 Nov 2020

  118. 118.

    Revilla M, Friggens NC, Broudiscou LP, Lemonnier G, Blanc F, Ravon L, Mercat MJ, Billon Y, Rogel-Gaillard C, Le Floch N, Estellé J, Muñoz-Tamayo R (2019) Towards the quantitative characterisation of piglets’ robustness to weaning: a modelling approach. Animal 13:2536–2546. https://doi.org/10.1017/S1751731119000843

    Article  Google Scholar 

  119. 119.

    Rehfeldt CKG (2006) Consequences of birth weight for postnatal growth performance and carcass quality in pigs as related to myogenesis. J Anim Sci 84(Suppl):E113–E123. https://doi.org/10.2527/2006.8413_supple113x

    Article  Google Scholar 

  120. 120.

    Collins CL, Pluske JR, Morrison RS, McDonald TN, Smits RJ, Henman DJ, Stensland I, Dunshea FR (2017) Post-weaning and whole-of-life performance of pigs is determined by live weight at weaning and the complexity of the diet fed after weaning. Anim Nutr 3:372–379. https://doi.org/10.1016/j.aninu.2017.01.001

    Article  Google Scholar 

  121. 121.

    Krieter JKE (1989) Growth, feed intake and mature size in Large White and Pietrain pigs. J Anim Breed Genet 106:300–311. https://doi.org/10.1111/j.1439-0388.1989.tb00244.x

    Article  Google Scholar 

  122. 122.

    Danfær A, Strathe AB (2012) Chapter 3: Quantitative and physiological aspects of pig growth. In Læreborg I Fysiologi. https://svineproduktion.dk/Services/Undervisningsmateriale2. Accessed 14 Sep 2020

  123. 123.

    Barbato GF (1991) Genetic architecture of growth curve parameters in chickens. Theor Appl Genet 83(1):24–32

    CAS  Article  Google Scholar 

  124. 124.

    Mortola JP (2010) Small birth weight does not compromise ventilatory chemosensitivity in the 1-day old hatchling. Respir Physiol Neurobiol 172:206–209. https://doi.org/10.1016/j.resp.2010.05.014

    Article  Google Scholar 

  125. 125.

    Narushin VGTC (2003) Sigmoid model for the evaluation of growth and production curves in laying hens. Biosyst Eng 84:343–348. https://doi.org/10.1016/S1537-5110(02)00286-6

    Article  Google Scholar 

  126. 126.

    Renema RA, Robinson FE, Goerzen PR, Zuidhof MJ (2001) Effects of altering growth curve and age at photostimulation in female broiler breeders. 2. Egg production parameters. Can J Anim Sci 4:477–486

    Article  Google Scholar 

  127. 127.

    Şengül TKS (2005) Non-linear models for growth curves in Large White turkeys. Turk J Vet Anim Sci 29(2):331–337

    Google Scholar 

  128. 128.

    Knižetova H, Hyanek J, Kniže B, Prochazkova H (1991) Analysis of growth curves of fowl. II. Ducks. Br Poult Sci 32:1039–1053. https://doi.org/10.1080/00071669108417428

    Article  Google Scholar 

  129. 129.

    Hois C (2004) Feldstudie zur Gewichtsentwicklung und Gewichtsschätzung beim wachsenden Pferd. Dissertation, Ludwig-Maximilian Universität

  130. 130.

    Rogers CW, Gee EK, Faram TL (2004) The effect of two different weaning procedures on the growth of pasture-reared thoroughbred foals in New Zealand. N Z Vet J 52:401–403. https://doi.org/10.1080/00480169.2004.36458

    CAS  Article  Google Scholar 

  131. 131.

    Waheed A, Khan MS, Ali S, Sarwar M (2011) Estimation of growth curve parameters in Beetal goats. Arch Tierz 54(3):287–296

    Google Scholar 

  132. 132.

    Mellado M, Meza-Herrera CA, Arévalo JR, De Santiago-Miramontes MA, Rodríguez A, Luna-Orozco JR, Veliz-Deras FG (2011) Erratum to: Relationship between litter birthweight and litter size in five goat genotypes. Anim Prod Sci 51:490. https://doi.org/10.1071/AN10112_ER

    Article  Google Scholar 

  133. 133.

    Lu CDPMJ (1988) Milk feeding and weaning of goat kids—a review. Small Ruminant Res 1:105–112

    Article  Google Scholar 

  134. 134.

    Sidwell GM, Miller LR (2019) Production in some pure breeds of sheep and their crosses. II Birth weights and weaning weights of lambs. J Anim Sci 32(6):1090–1095

    Article  Google Scholar 

  135. 135.

    Blasco A, Piles M, Varona L (2003) A Bayesian analysis of the effect of selection for growth rate on growth curves in rabbits. Genet Sel Evol 35:21–41. https://doi.org/10.1186/1297-9686-35-1-21

    Article  Google Scholar 

  136. 136.

    Poigner J, Szendrö ZS, Levai A, Radnai I, Biro-Nemeth E (2000) Effect of birth weight and litter size on growth and mortality in rabbits. World Rabbit Sci 8:17–22. https://doi.org/10.4995/wrs.2000.413

    Article  Google Scholar 

  137. 137.

    Bundesanstalt für Landwirtschaft und Ernährung BLE (2020) Bericht zur Markt und Versorgungslage Futtermittel 2020. Bonn (Germany): BLE. https://www.ble.de/SharedDocs/Downloads/DE/BZL/Daten-Berichte/Futter/2020BerichtFuttermittel.pdf?__blob=publicationFile&v=3. Accessed 14 Sep 2020

  138. 138.

    Afonso ER, Nacimento RA, Palhares JCP, Gameiro AH (2020) How can nutritional strategies and feed technologies in pig production affect the logistical costs of manure distribution? Revista Brasileira Zootecnia. https://doi.org/10.37496/rbz4920190045

    Article  Google Scholar 

  139. 139.

    Dämmgen U, Brade W, Haenel HD, Rösemann C, Kleine-Klausing H, Webb A, Berk A (2018) Pork production in Thuringia—management effects on ammonia and greenhouse gas emissions. 1. Depiction of the state in 2015. Appl Agric For Res. https://doi.org/10.3220/LBF1547712205000

    Article  Google Scholar 

  140. 140.

    Council Directive of 12 December 1991 concerning the protection of waters against pollution caused by nitrates from agricultural sources (91 / 676 /EEC). https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=celex%3A31991L0676. Accessed 14 Sep 2020

  141. 141.

    Clark B, Stewart GB, Panzone LA (2016) A systematic review of public attitudes, perceptions and behaviours towards production diseases associated with farm animal welfare. J Agric Environ Ethics 29:455–478. https://doi.org/10.1007/s10806-016-9615-x

    Article  Google Scholar 

  142. 142.

    Clark B, Panzone LA, Stewart GB, Kyriazakis I, Niemi JK, Latvala T (2019) Consumer attitudes towards production diseases in intensive production systems. PLoS ONE 14:e0210432. https://doi.org/10.1371/journal.pone.0210432

    CAS  Article  Google Scholar 

  143. 143.

    Regulation (EC) No 889/2008 of 5 September 2008 laying down detailed rules for the implementation of Council Regulation (EC) No 834/2007 on organic production and labelling of organic products with regard to organic production, labelling and control. https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32008R0889&from=DE. Accessed 14 Sep 2020

  144. 144.

    Bohnenkemper O Exkrementenanfall und -verwertung in der Eiererzeugung. In Brade W, Flachowsky G, Schrader L (eds) Legehuhnzucht und Eiererzeugung—Empfehlungen für die Praxis. https://www.thuenen.de/media/publikationen/landbauforschung-sonderhefte/lbf_sh322.pdf. Accessed 12 Oct 2020

  145. 145.

    Schimpf H, Stolpe P, Schulze H Richtwertsammlung Düngerecht. Eds Landesanstalt für Landwirtschaft und Gartenbau Sachsen-Anhalt. https://llg.sachsen-anhalt.de/fileadmin/Bibliothek/Politik_und_Verwaltung/MLU/LLFG/Dokumente/04_themen/pfl_ernaehr_duengung/Richtwerte/2019_rw_teil6_duengerecht.pdf. Accessed 26 Feb 2021

  146. 146.

    Haupt R, Schmid S M, Heinemann C, Steinhoff-Wagner J (2020, published virtual) Update of input parameters for the PEC calculation, SETAC Europe, 30th Annual Meeting

  147. 147.

    Hemme M, Käsbohrer A, von Münchhausen C, Hartmann M, Merle R, Kreienbrock L (2017) Unterschiede in der Berechnung des betriebsbezogenen Antibiotika-Einsatzes in Monitoringsystemen in Deutschland—Eine Übersicht. Berl Münch Tierärztl Wochenschr. https://doi.org/10.2376/0005-9366-16065

    Article  Google Scholar 

  148. 148.

    Lillehoj H, Liu Y, Calsamiglia S, Fernandez-Miyakawa ME, Chi F, Cravens RL, Oh S, Gay CG (2018) Phytochemicals as antibiotic alternatives to promote growth and enhance host health. Vet Res 49:1–18

    Article  Google Scholar 

  149. 149.

    Fischer K, Sjöström K, Stiernström A, Emanuelson U (2019) Dairy farmers’ perspectives on antibiotic use: a qualitative study. J Dairy Sci 102:2724–2737. https://doi.org/10.3168/jds.2018-15015

    CAS  Article  Google Scholar 

  150. 150.

    Piepers S, De Vliegher S (2018) Alternative approach to mastitis management—how to prevent and control mastitis without antibiotics? Braz J Vet Res Anim Sci 55:1–22. https://doi.org/10.11606/issn.1678-4456.bjvras.2018.137149

    Article  Google Scholar 

  151. 151.

    McParland S, Dillon PG, Flynn J, Ryan N, Arkins S, Kennedey A (2019) Effect of using internal teat sealant with or without antibiotic therapy at dry-off on subsequent somatic cell count and milk production. J Dairy Sci 102:4464–4475. https://doi.org/10.3168/jds.2018-15195

    CAS  Article  Google Scholar 

  152. 152.

    Kruip TAM, Morice H, Robert M, Ouweltjes W (2002) Robotic milking and its effect on fertility and cell counts. J Dairy Sci 85:2576–2581

    CAS  Article  Google Scholar 

  153. 153.

    Bortacki P, Kujawiak R, Czerniawska-Piatkowska E, Kirdar SS, Wójcik J, Grzesiak W (2017) Impact of milking frequency on yield, chemical composition and quality of milk in high producing dairy herd. Mljekarstvo 67:226–230. https://doi.org/10.15567/mljekarstvo.2017.0307

    CAS  Article  Google Scholar 

  154. 154.

    Qin J, Xiong H, Ma H (2019) Effects of different fertilizers on residues of oxytetracycline and microbial activity in soil. Environ Sci Pollut Res 26:161–170

    CAS  Article  Google Scholar 

  155. 155.

    Zhu L, Cao X, Xu Q et al (2018) Evaluation of the antibacterial activity of tilmicosin-SLN against Streptococcus agalactiae: in vitro and in vivo studies. Int J Nanomed 13:4747–4755. https://doi.org/10.2147/IJN.S168179

    CAS  Article  Google Scholar 

  156. 156.

    Arikan OA, Sikora LJ, Mulbry W et al (2006) The fate and effect of oxytetracycline during the anaerobic digestion of manure from therapeutically treated calves. Process Biochem 41:1637–1643. https://doi.org/10.1016/j.procbio.2006.03.010

    CAS  Article  Google Scholar 

  157. 157.

    Ferreira CSG, Nunes BA, Henriques-Almeida JMdM et al (2007) Acute toxicity of oxytetracycline and florfenicol to the microalgae Tetraselmis chuii and to the crustacean Artemia parthenogenetica. Ecotoxicol Environ Saf 67:452–458. https://doi.org/10.1016/j.ecoenv.2006.10.006

    CAS  Article  Google Scholar 

  158. 158.

    Wang Y-W, Tang H, Wu D et al (2016) Enhanced bactericidal toxicity of silver nanoparticles by the antibiotic gentamicin. Environ Sci Nano 3:788–798. https://doi.org/10.1039/C6EN00031B

    CAS  Article  Google Scholar 

  159. 159.

    Xie S, Wang F, Wang Y et al (2011) Acute toxicity study of tilmicosin-loaded hydrogenated castor oil-solid lipid nanoparticles. Part Fibre Toxicol 8:33. https://doi.org/10.1186/1743-8977-8-33

    CAS  Article  Google Scholar 

  160. 160.

    Halling-Sørensen B, Sengeløv G, Tjørnelund J (2002) Toxicity of tetracyclines and tetracycline degradation products to environmentally relevant bacteria, including selected tetracycline-resistant bacteria. Arch Environ Contam Toxicol 42:263–271

    Article  Google Scholar 

  161. 161.

    Tierschutzgesetz in der Fassung der Bekanntmachung vom 18. Mai 2006 (BGBl. I S. 1206, 1313), das zuletzt durch Artikel 280 der Verordnung vom 19. Juni 2020 (BGBl. I S. 1328) geändert worden ist, (Animal protection law). https://www.gesetze-im-internet.de/tierschg/BJNR012770972.html. Accessed 14 Sep 2020

  162. 162.

    Directive 2001/82/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to veterinary medicinal products

  163. 163.

    Pozzi PSAGL (2012) Reproductive diseases in sows. Isr J Vet Med 67:24–33

    Google Scholar 

  164. 164.

    Agunos A, Carson C, Léger D (2013) Antimicrobial therapy of selected diseases in turkeys, laying hens, and minor poultry species in Canada. Can Vet J 54:1041–1052

    Google Scholar 

Download references

Acknowledgements

The authors thank the student assistants at the Institute of Animal Science for their support during the research, especially C. Brune, A. Farwick and T. Steegmann. We gratefully acknowledge constructive discussions and specific questions in particular by Dr. S. Lehmann, Dr. W. Koch, Dr. G. Speichert, Dr. A. Hein and Dr. S. Hickmann during the study and their critical review of the manuscript.

Funding

Open Access funding enabled and organized by Projekt DEAL. The present study was funded by the Federal Environment Agency (Project no. 121113).

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JSW and CH were involved in the funding acquisition. CH, RH, and JSW conceptualized the data search. RH and JSW drafted the manuscript. JSW, RH, MG and RB created the figures. SMS, JJH, CH, and JSW reviewed the manuscript with major contribution and JSW edited the draft. All authors read and approved the final manuscript.

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Correspondence to Julia Steinhoff-Wagner.

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The authors declare that they have no conflict of interest. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Federal Environment Agency.

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Supplementary Information

Additional file 1: Table S1.

Equation for calculation of PECsoil initial according to the European Medicine Agency [22]. Table S2. Percentage herd treatment for various groups of VMPs, according to EMA [22]. Table S3. Default values used in the calculation of PECsoil for intensively reared animals, according to EMA [22]. Table S4. Default values used for calculating PECsoil for pasture animals, according to EMA [22]. Table S5. Daily dung production data of pasture animals, according to EMA [22]. Table S6. Default values used for calculating the PECsoil refined following degradation in manure, according to EMA [22]. Table S7. Overview of various regulations and directives of the European Union (EU) and Germany (as a representative European country) researched in this study in regards to the classification of farm animal species and framework for husbandry and management. Table S8. Overview of various feeding studies on N consumption and excretion in dairy cows.

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Haupt, R., Heinemann, C., Hayer, J.J. et al. Critical discussion of the current environmental risk assessment (ERA) of veterinary medicinal products (VMPs) in the European Union, considering changes in animal husbandry. Environ Sci Eur 33, 128 (2021). https://doi.org/10.1186/s12302-021-00554-3

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Keywords

  • Environmental risk assessment (ERA)
  • Predicted environmental concentration (PEC)
  • Animal production
  • Veterinary medicinal product (VMP)
  • Environmental impact assessment (EIA)