Toxicity for Aquatic Organisms of Antiretroviral Tenofovir Disoproxil

Abstract

Tenofovir disoproxil fumarate is a prodrug, i.e. inative substance converted in vivo, after absorption to the active form de-esterified tenofovir, which acts as an inhibitor of viral reverse transcriptase. To better understand the toxic effects of these drugs in the environment, three organisms were tested, the effective concentration (EC 50 ) and inhibitory concentration (IC 50 ) of tenofovir disoproxil that resulted in 50% growth inhibition of Microcystis novacekii, 50% immobilization of Artemia salina, and 50% loss of bioluminescence of Aliivibrio fischeri were evaluated. The EC 50 value after 96 h of treatment for the cyanobacterium was 161.01 (156.81 -165.21) mg·L −1 ; the IC 50 value for A. salina after 24 h of treatment was 111.82 (103.18 -120.45) mg·L −1 ; and the IC 50 at 15 min for A. fischeri was 14.83 (13.87 -15.79) mg·L −1 . The test organism most sensitive to the drug was A. fischeri, indicating the importance of using representative models at different trophic levels to assess the potential risk of drugs for environmental toxicity. These results highlight the possible effect of tenofovir disoproxil on decomposer organisms, which may contribute to the environmental persistence of this drug.

Occurrence and Effects of Antimicrobials Drugs in Aquatic Ecosystems

“…As for antivirals. Almeida et al [91] and Silva et al [92] reported growth inhibition of Raphidocelis subcapitata and Microcystis novacekii after exposure to acyclovir, efavirenz, lamivudine, zidovudine and tenofovir (Table 3). The effect of the antifungals propiconazole and tebuconazole on the growth and antioxidant response of the microalga Chlorella pyrenoidosa was evaluated by Nong et al [93], identifying that doses of 100, 200 and 1000 µg L −1 were enough to inhibit growth.…”

Os efeitos tóxicos do antirretroviral nevirapina e um medicamento à base de nevirapina para organismos aquáticos

“…A mortalidade de A. salina ocorreu em concentração de NVP três vezes menor que a descrita por Boehringer Ingelheim (2015) para o microcrustáceo de água doce D. Magna, sugerindo que para esse IFA, a espécie A. salina foi o modelo mais sensível para estimar a toxicidade (Onbasili & Duman, 2010;Libralato et al, 2016;Oliveira et al;. Vale ressaltar que, de acordo com a literatura, comparando-se o risco tóxico entre os ARVs, em termos de CE50%, a NVP oferece maior risco para A. salina que o abacavir (CE50%> 100,0 mg L -1 ) (Minguez et al, 2016) e que o tenofovir desoproxil (CE50% 111,82 | 103,45 | mg L -1 ) (Silva et al, 2019).…”

“…Na literatura foram descritos outros IFAs com o mesmo nível de concentração efetiva da NVP para inibição em 50% da viabilidade da espécie: o diclofenaco (CE50% 14,04 mg L -1 ) (Czech et al, 2014), o metoprolol (CE50% 14,48 mg L -1 ) (de García et al, 2016), a sertralina (CE50% de 9,2 mg L -1 ) (Minagh et al, 2009) e o tenofovir (CE50% de 14,83 mg L -1 ) (Silva et al, 2019). Outros apresentaram toxicidade pouco relevante como a carbamazepina (CE50% 78,4 mg L -1 ) (Jos et al, 2003), ibuprofeno (CE50% 75,19 mg L -1 ) (Dong et al, 2019) e a azitromicina (EC50% 237,54 mg L -1 ) (Dong et al, 2019).…”

Occurrence, Fate, Effects, and Risks of Dexamethasone: Ecological Implications Post-COVID-19

“…Further, C. dubia was more sensitive compared to algae, irrespective of the parent drug or formed TPs. Thus, inhibition of C. dubia growth may result in the deleterious disruption of the food chain as it forms a link between primary producers (e.g., algae) and aquatic vertebrates (e.g., fish) [90].…”