18. Ji K, Liu X, Lee S, Kang S, Kho Y, Giesy JP, Choi K (2013) Effects of non-steroidal antiinflammatory drugs on hormones and genes of the hypothalamic-pituitary-gonad axis, and
reproduction of zebrafish. J Hazard Mater 254–255(1):242–251. https://doi.org/10.1016/j.
jhazmat.2013.03.036
19. Embry MR, Belanger SE, Braunbeck TA, Galay-burgos M, Halder M, Hinton DE et al (2010)
The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and
scientific research. Aquat Toxicol 97(0349):79–87. https://doi.org/10.1016/j.aquatox.2009.12.
008
20. Pritchard JB (1993) Aquatic toxicology: past, present, and prospects. Environ Health Perspect
100:249–257. https://doi.org/10.1289/ehp.93100249
21. Mohammed A (2013) Why are early life stages of aquatic organisms more sensitive to toxicants
than adults? In: New insights into toxicity and drug testing, vol. 1. p 13. https://doi.org/10.5772/
55187
22. Homfray T, Farndon PA (2015) Fetal anomalies – the Geneticist’s approach. In: Twining’s
textbook of fetal abnormalities3rd edn, pp 139–160. https://doi.org/10.1016/B978-0-70204591-2.00007-3
23. Wells P, Bhuller Y, Chen C, Jeng W, Kasapinovic S, Kennedy J, Nicol C (2005) Molecular and
biochemical mechanisms in teratogenesis involving reactive oxygen species. Toxicol Appl
Pharmacol 207(2):354–366. https://doi.org/10.1016/j.taap.2005.01.061
24. Laher I (2014) Systems biology of free radicals and antioxidants. In: Laher I (ed.) Systems
biology of free radicals and antioxidants, vol 9783642300. https://doi.org/10.1007/978-3-64230018-9
25. van Gelder MMHJ, van Rooij IALM, Miller RK, Zielhuis GA, de Jong-van den Berg LTW,
Roeleveld N (2010) Teratogenic mechanisms of medical drugs. Hum Reprod Update 16
(4):378–394. https://doi.org/10.1093/humupd/dmp052
26. Roberts JL (2001) Analgesic–antipyretic and anti-inflammatory agents and drugs employed in
the treatment of gout. In: Gilman AG, Hardman JG (eds) Goodman and Gilman’s the pharmacological basis of therapeutics10th edn. McGraw Hill, New York, pp 687–731
27. Stülten D, Zühlke S, Lamshöft M, Spiteller M (2008) Occurrence of diclofenac and selected
metabolites in sewage effluents. Sci Total Environ 5(405):310–316. https://doi.org/10.1016/j.
scitotenv.2008.05.036
28. Peltzer PM, Lajmanovich RC, Martinuzzi C, Attademo AM, Curi LM, Sandoval MT (2019)
Biotoxicity of diclofenac on two larval amphibians: assessment of development, growth,
cardiac function and rhythm, behavior and antioxidant system. Sci Total Environ
683:624–637. https://doi.org/10.1016/j.scitotenv.2019.05.275
29. Balbi T, Montagna M, Fabbri R, Carbone C, Franzellitti S, Fabbri E, Canesi L (2018)
Diclofenac affects early embryo development in the marine bivalve Mytilus galloprovincialis.
Sci Total Environ 642:601–609. https://doi.org/10.1016/j.scitotenv.2018.06.125
30. Chen J-B, Gao H-W, Zhang Y-L, Zhang Y, Zhou X-F, Li C-Q, Gao H-P (2015) Developmental
toxicity of Diclofenac and elucidation of gene regulation in zebrafish (Danio rerio). Sci Rep 4
(1):4841. https://doi.org/10.1038/srep04841
31. Schwarz S, Schmieg H, Scheurer M, Köhler H-R, Triebskorn R (2017) Impact of the NSAID
diclofenac on survival, development, behaviour and health of embryonic and juvenile stages of
brown trout, Salmo trutta fario. Sci Total Environ 607–608:1026–1036. https://doi.org/10.1016/
j.scitotenv.2017.07.042
32. Pohl J, Ahrens L, Carlsson G, Golovko O, Norrgren L, Weiss J, Örn S (2019) Embryotoxicity of
ozonated diclofenac, carbamazepine, and oxazepam in zebrafish (Danio rerio). Chemosphere
225:191–199. https://doi.org/10.1016/j.chemosphere.2019.03.034
33. Hallare AV, Köhler H-R, Triebskorn R (2004) Developmental toxicity and stress protein
responses in zebrafish embryos after exposure to diclofenac and its solvent, DMSO.
Chemosphere 56(7):659–666. https://doi.org/10.1016/j.chemosphere.2004.04.007
Teratogenesis and Embryotoxicity Induced by Non-steroidal Anti-Inflammatory. . .
127
reproduction of zebrafish. J Hazard Mater 254–255(1):242–251. https://doi.org/10.1016/j.
jhazmat.2013.03.036
19. Embry MR, Belanger SE, Braunbeck TA, Galay-burgos M, Halder M, Hinton DE et al (2010)
The fish embryo toxicity test as an animal alternative method in hazard and risk assessment and
scientific research. Aquat Toxicol 97(0349):79–87. https://doi.org/10.1016/j.aquatox.2009.12.
008
20. Pritchard JB (1993) Aquatic toxicology: past, present, and prospects. Environ Health Perspect
100:249–257. https://doi.org/10.1289/ehp.93100249
21. Mohammed A (2013) Why are early life stages of aquatic organisms more sensitive to toxicants
than adults? In: New insights into toxicity and drug testing, vol. 1. p 13. https://doi.org/10.5772/
55187
22. Homfray T, Farndon PA (2015) Fetal anomalies – the Geneticist’s approach. In: Twining’s
textbook of fetal abnormalities3rd edn, pp 139–160. https://doi.org/10.1016/B978-0-70204591-2.00007-3
23. Wells P, Bhuller Y, Chen C, Jeng W, Kasapinovic S, Kennedy J, Nicol C (2005) Molecular and
biochemical mechanisms in teratogenesis involving reactive oxygen species. Toxicol Appl
Pharmacol 207(2):354–366. https://doi.org/10.1016/j.taap.2005.01.061
24. Laher I (2014) Systems biology of free radicals and antioxidants. In: Laher I (ed.) Systems
biology of free radicals and antioxidants, vol 9783642300. https://doi.org/10.1007/978-3-64230018-9
25. van Gelder MMHJ, van Rooij IALM, Miller RK, Zielhuis GA, de Jong-van den Berg LTW,
Roeleveld N (2010) Teratogenic mechanisms of medical drugs. Hum Reprod Update 16
(4):378–394. https://doi.org/10.1093/humupd/dmp052
26. Roberts JL (2001) Analgesic–antipyretic and anti-inflammatory agents and drugs employed in
the treatment of gout. In: Gilman AG, Hardman JG (eds) Goodman and Gilman’s the pharmacological basis of therapeutics10th edn. McGraw Hill, New York, pp 687–731
27. Stülten D, Zühlke S, Lamshöft M, Spiteller M (2008) Occurrence of diclofenac and selected
metabolites in sewage effluents. Sci Total Environ 5(405):310–316. https://doi.org/10.1016/j.
scitotenv.2008.05.036
28. Peltzer PM, Lajmanovich RC, Martinuzzi C, Attademo AM, Curi LM, Sandoval MT (2019)
Biotoxicity of diclofenac on two larval amphibians: assessment of development, growth,
cardiac function and rhythm, behavior and antioxidant system. Sci Total Environ
683:624–637. https://doi.org/10.1016/j.scitotenv.2019.05.275
29. Balbi T, Montagna M, Fabbri R, Carbone C, Franzellitti S, Fabbri E, Canesi L (2018)
Diclofenac affects early embryo development in the marine bivalve Mytilus galloprovincialis.
Sci Total Environ 642:601–609. https://doi.org/10.1016/j.scitotenv.2018.06.125
30. Chen J-B, Gao H-W, Zhang Y-L, Zhang Y, Zhou X-F, Li C-Q, Gao H-P (2015) Developmental
toxicity of Diclofenac and elucidation of gene regulation in zebrafish (Danio rerio). Sci Rep 4
(1):4841. https://doi.org/10.1038/srep04841
31. Schwarz S, Schmieg H, Scheurer M, Köhler H-R, Triebskorn R (2017) Impact of the NSAID
diclofenac on survival, development, behaviour and health of embryonic and juvenile stages of
brown trout, Salmo trutta fario. Sci Total Environ 607–608:1026–1036. https://doi.org/10.1016/
j.scitotenv.2017.07.042
32. Pohl J, Ahrens L, Carlsson G, Golovko O, Norrgren L, Weiss J, Örn S (2019) Embryotoxicity of
ozonated diclofenac, carbamazepine, and oxazepam in zebrafish (Danio rerio). Chemosphere
225:191–199. https://doi.org/10.1016/j.chemosphere.2019.03.034
33. Hallare AV, Köhler H-R, Triebskorn R (2004) Developmental toxicity and stress protein
responses in zebrafish embryos after exposure to diclofenac and its solvent, DMSO.
Chemosphere 56(7):659–666. https://doi.org/10.1016/j.chemosphere.2004.04.007
Teratogenesis and Embryotoxicity Induced by Non-steroidal Anti-Inflammatory. . .
127