the financial support to CESAM (UID/AMB/50017/2019) and to FCT/MEC through national funds
and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020.
References
1. Hinson JA, Roberts DW, James LP (2010) Mechanisms of acetaminophen-induced liver
necrosis. Handb Exp Pharmacol 196:369–405. https://doi.org/10.1007/978-3-642-00663-0_12
2. Diener H-C, Schneider R, Aicher B (2008) Per-capita consumption of analgesics: a ninecountry survey over 20 years. J Headache Pain 9:225–231
3. Sebastine IM, Wakeman RJ (2003) Consumption and environmental hazards of pharmaceutical
substances in the UK. Process Saf Environ Protect 81:229–235
4. Ebele AJ, Abdallah MA-E, Harrad S (2017) Pharmaceuticals and personal care products
(PPCPs) in the freshwater aquatic environment. Emerg Contam 3:1–16. https://doi.org/10.
1016/j.emcon.2016.12.004
5. Józwiak-Bebenista M, Nowak JZ (2014) Paracetamol: mechanism of action, applications and
safety concern. Acta Pol Pharm Drug Res 71(1):11–23
6. De Martino M, Chiarugi A (2015) Recent advances in pediatric use of oral paracetamol in fever
and pain management. Pain Ther 4(2):149–168. https://doi.org/10.1007/s40122-015-0040-z
7. Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF (2013) The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent
pharmacological findings. Inflammopharmacology 21(3):201–232. https://doi.org/10.1007/
s10787-013-0172-x
8. Gunnell D, Murray V, Hawton K (2000) Use of paracetamol (acetaminophen) for suicide and
nonfatal poisoning: worldwide patterns of use and misuse. Suicide Life Threat Behav 30
(4):313–326
9. Lau SM, McGuire TM, van Driel ML (2016) Consumer concerns about paracetamol: a
retrospective analysis of a medicines call centre. BMJ Open 6(6):e010860. https://doi.org/10.
1136/bmjopen-2015-010860
10. Zyoud SH, Al-Jabi SW, Sweileh WM (2015) Worldwide research productivity of paracetamol
(acetaminophen) poisoning: a bibliometric analysis (2003–2012). Hum Exp Toxicol 34
(1):12–23. https://doi.org/10.1177/0960327114531993
11. Jaeschke H, Bajt ML (2006) Intracellular signaling mechanisms of acetaminophen-induced
liver cell death. Toxicol Sci 89(1):31–41
12. Jaeschke H, Knight TR, Bajt ML (2003) The role of oxidant stress and reactive nitrogen species
in acetaminophen hepatotoxicity. Toxicol Lett 144:279–288
13. Tittarelli R, Pellegrini M, Scarpellini MG, Marinelli E, Bruti V, Di Luca NM, Busardò FP,
Zaami S (2017) Hepatotoxicity of paracetamol and related Fatalities. Eur Rev Med Pharmacol
Sci 21(1 Suppl):95–101
14. McJunkin B, Barwick KW, Little WC, Winfield JB (1976) Fatal massive hepatic necrosis
following acetaminophen overdose. JAMA 236(16):1–2
15. Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, Reisch JS, Schiødt FV,
Ostapowicz G, Shakil AO, Lee WM (2005) Acetaminophen-induced acute liver failure: results
of a United States multicenter, prospective study. Hepatology 42:13641372. https://doi.org/10.
1002/hep.20948
16. Lee WM (2008) Acetaminophen-related acute liver failure in the United States. Hepatol Res 38
(Suppl. 1):3–8. https://doi.org/10.1111/j.1872-034X.2008.00419.x
17. Hadi M, Dragovic S, Van Swelm R, Herpers B, Van de Water B, FGM R, GMM G (2013)
AMAP, the alleged non-toxic isomer of acetaminophen, is toxic in rat and human liver. Arch
Toxicol 87(1):155–165. https://doi.org/10.1007/s00204-012-0924-1
Ecotoxicological Effects of the Drug Paracetamol: A Critical Review of Past. . .
141
and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020.
References
1. Hinson JA, Roberts DW, James LP (2010) Mechanisms of acetaminophen-induced liver
necrosis. Handb Exp Pharmacol 196:369–405. https://doi.org/10.1007/978-3-642-00663-0_12
2. Diener H-C, Schneider R, Aicher B (2008) Per-capita consumption of analgesics: a ninecountry survey over 20 years. J Headache Pain 9:225–231
3. Sebastine IM, Wakeman RJ (2003) Consumption and environmental hazards of pharmaceutical
substances in the UK. Process Saf Environ Protect 81:229–235
4. Ebele AJ, Abdallah MA-E, Harrad S (2017) Pharmaceuticals and personal care products
(PPCPs) in the freshwater aquatic environment. Emerg Contam 3:1–16. https://doi.org/10.
1016/j.emcon.2016.12.004
5. Józwiak-Bebenista M, Nowak JZ (2014) Paracetamol: mechanism of action, applications and
safety concern. Acta Pol Pharm Drug Res 71(1):11–23
6. De Martino M, Chiarugi A (2015) Recent advances in pediatric use of oral paracetamol in fever
and pain management. Pain Ther 4(2):149–168. https://doi.org/10.1007/s40122-015-0040-z
7. Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF (2013) The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent
pharmacological findings. Inflammopharmacology 21(3):201–232. https://doi.org/10.1007/
s10787-013-0172-x
8. Gunnell D, Murray V, Hawton K (2000) Use of paracetamol (acetaminophen) for suicide and
nonfatal poisoning: worldwide patterns of use and misuse. Suicide Life Threat Behav 30
(4):313–326
9. Lau SM, McGuire TM, van Driel ML (2016) Consumer concerns about paracetamol: a
retrospective analysis of a medicines call centre. BMJ Open 6(6):e010860. https://doi.org/10.
1136/bmjopen-2015-010860
10. Zyoud SH, Al-Jabi SW, Sweileh WM (2015) Worldwide research productivity of paracetamol
(acetaminophen) poisoning: a bibliometric analysis (2003–2012). Hum Exp Toxicol 34
(1):12–23. https://doi.org/10.1177/0960327114531993
11. Jaeschke H, Bajt ML (2006) Intracellular signaling mechanisms of acetaminophen-induced
liver cell death. Toxicol Sci 89(1):31–41
12. Jaeschke H, Knight TR, Bajt ML (2003) The role of oxidant stress and reactive nitrogen species
in acetaminophen hepatotoxicity. Toxicol Lett 144:279–288
13. Tittarelli R, Pellegrini M, Scarpellini MG, Marinelli E, Bruti V, Di Luca NM, Busardò FP,
Zaami S (2017) Hepatotoxicity of paracetamol and related Fatalities. Eur Rev Med Pharmacol
Sci 21(1 Suppl):95–101
14. McJunkin B, Barwick KW, Little WC, Winfield JB (1976) Fatal massive hepatic necrosis
following acetaminophen overdose. JAMA 236(16):1–2
15. Larson AM, Polson J, Fontana RJ, Davern TJ, Lalani E, Hynan LS, Reisch JS, Schiødt FV,
Ostapowicz G, Shakil AO, Lee WM (2005) Acetaminophen-induced acute liver failure: results
of a United States multicenter, prospective study. Hepatology 42:13641372. https://doi.org/10.
1002/hep.20948
16. Lee WM (2008) Acetaminophen-related acute liver failure in the United States. Hepatol Res 38
(Suppl. 1):3–8. https://doi.org/10.1111/j.1872-034X.2008.00419.x
17. Hadi M, Dragovic S, Van Swelm R, Herpers B, Van de Water B, FGM R, GMM G (2013)
AMAP, the alleged non-toxic isomer of acetaminophen, is toxic in rat and human liver. Arch
Toxicol 87(1):155–165. https://doi.org/10.1007/s00204-012-0924-1
Ecotoxicological Effects of the Drug Paracetamol: A Critical Review of Past. . .
141