Table 1 Non-target environmental effects of pharmaceuticals used in MDA programs

Ivermectin (antiparasitic)

Dung beetles (insects)

100 μg/kg of ivermectin

Reduced species richness, abundance, and biomass

Field (Spain)

Spiked dung exposed in the field

 2 seasons (spring and autumn)

 Sampling 12 and 48 h after dung placement

[87]

40 µg/kg/day

Reduced dung degradation associated with absence of dung-degrading insects

 Field (England)

Faeces of calves fitted with rumenal boluses delivering ivermectin

100 days

[89]

1.0, 3.3, 10.0, 33.3, 100.0 and 200.0 μg/kg

Impaired locomotion, reduced foraging success, death

Laboratory

Non-contaminated bovine dung from ivermectin-free cattle

12−18 days

[91]

Dung insect community (Diptera and Hymenoptera)

6.6 µg/kg fresh dung

Reduced biodiversity

Field (Switzerland)

Fresh cattle dung collected on the local farms

24 cattle farms; repeated over 3 seasons

[88]

Azithromycin (antibiotic)

Algae (phytoplankton)

0.5 and 1 μg/L (low)

5–100 μg/L (high)

Accelerated growth (low dose)

Inhibited growth and disrupted photosynthesis (high dose)

Laboratory

Algae grown in 1 L flasks

96 h

[94]

LC50

Growth inhibition

Laboratory

 13 antibiotics tested

 Algae in the exponential growth phase exposed to antibiotics

 250 ml conical flasks used

96 h

[95]

Daphnia (zooplankton)

1, 10, 50, 100 and 200 mg/L

Altered feeding behavior and nutrition accumulation

Laboratory

Different exposure pathways investigated (aqueous phase and food phase)

Up to 96 h

[96]

European sea bass (fish)

0.625, 1.25, 2.5, 5, 10 and 20 mg/L

Larval mortality and morphological abnormalities (at 20 mg/L)

Laboratory

Sea bass obtained from aquaculture, kept in 1 L aquaria with seawater

 96 h for acute toxicity

 4 and 14 days for chronic toxicity

[97]

Zebrafish (fish)

10 and 50 μg/L

Cardiotoxicity

Laboratory

Macrolide antibiotics dissolved in embryos medium

Up to 5 days post fertilization of fish embryos

[98]

Tilapia (fish)

1, 50 and 100 mg/L

Considered non-toxic (with moderate liver damage)

Laboratory

 Fish obtained from aquaculture

 3 fish/aquarium; 1 g fish/L

48 h (acute toxicity)

14 days (chronic exposure)

[99]

Marine fish

N/A (field sample collection)

Bioaccumulation in livers

Field (China)

 7 wild fish species collected from Laizhou Bay, North China using bottom trawl

 Tissues dissected and tested for antibiotics

One time collection

[100]

Oyster, mussel, and clam (bivalve molluscs)

Field-sample collection

Bioaccumulation

Field and Laboratory (Spain)

 Molluscs field-collected

 Homogenized tissues tested

2 collections 1 month apart

[101]

Earthworms

0.0089

to 0.03 mg/kg

and 0.16 mg/kg

 No toxicity response

 Bioaccumulation of antibiotic in the tissues with potential of entry into food webs

Laboratory

 1 L Mason jars filled with soil

 Uses both environmentally relevant and unrealistically high concentrations

28 days

[102]

Radish, lettuce, and fescue grass (plants)

0.83 and 3.2 mg/kg

Minimal toxicity and bioaccumulation

Laboratory

Biosolids-amended soils and soils directly spiked with antibiotics

32 days after planting (radish); 46 days after planting (lettuce); 42 days after planting (fescue grass)

[103]

Microbial community

Low, medium, and high (based on Targeted

National Sewage Sludge Survey

Minimal toxicity

Laboratory

 Direct application of biosolids or antibiotic mixture to soil

 300 mL glass jars with soil

120 days

[102]

Other mixtures

Microbial community

0.1 or 10 mg/kg soil of antibiotic mixture containing azithromycin

Increase the abundance of novel antibiotic resistance genes identified via functional metagenomics in the soil

Field (Canada)

 Annual application

 Quadruplicate plots

8 years

[104]

Microbial community

75 dry t/ha of compost

Increase in gene targets for macrolide resistance, persisting in soil for up to 4 years

Field (Canada)

 One time application of compost

 4 blocks of 5 plots (12.2 m wide by 10 m long)

10 years

[105]