Hazard 8 P 3 B 3 T 2 Risk Insignificant
This summary information comes from Fass.
Persistence. Ritonavir is potentially persistent.
Bioaccumulation. Ritonavir has high potential for bioaccumulation.
Toxicity. Ritonavir has a high acute toxicity.
Risk. The use of ritonavir (sales data Sweden 2016) gives the risk insignificant.
Scientific discussion on Kaletra
Scientific discussion on Kaletra (lopinavir, ritonavir), Procedure No. EMEA/H/C/368/X/27 from 2006.
"PEC/PNEC ratio for ritonavir = 0.132, thus <1 and does not require further investigations per the phase II Tier B evaluation. Consequently, ritonavir is unlikely to represent a risk to the environment."
Assessment report for Kaletra
Assessment report for Kaletra 22 June 2017 EMA/CHMP/443456/2017.
"No updated environmental risk assessment for lopinavir and ritonavir has been provided. However, as stated in the EPAR of KALETRA that the lack of environmental risk assessment was considered acceptable since lopinavir degrades under UV-light and rapid breakdown is to be expected based on the molecular structure of lopinavir/ritonavir. Moreover, the MAH (Marketing Authorization Holder ed. note) provided data on the low incidence of HIV in children under 2 years of age in EU (< 300/year). This extension of indication constitutes a marginal increased in the environmental exposure and the PECsurfacewater value is below 0.01 µg/L based on the maximum daily dose. "
Fass environmental information
Fass environmental information for Kaletra from AbbVie (downloaded 2020-04-07).
Persistence: "Ritonavir did not show ready biodegradability or inherent biodegradability as defined by OECD 301 and ECHA guidance. [...] There are no data from simulation studies (OECD 308) or analytical monitoring data to demonstration elimination within the ECHA defined persistence half-life. Therefore, the summary phrase “ritonavir is potentially persistent” has been selected."
Bioaccumulation: "By the HPLC method, pH = 7.4, n = 2, Log Dow = 4.7. By the shake-flask method, pH = 7.4, 25 °C, n=3, Log Dow = 3.99. Log Dow at pH 7≥ 4.0 therefore, ritonavir has high potential for bioaccumulation."
Acute toxicity: There are data for 3 trophic levels, most sensitive crustacean (Daphnia magna) > 1500 microg/L. Comment: Values reported as greater than are not according to the guidelines. The actual value may be lower.
PEC/PNEC is based on sales data in Sweden in year 2016. PEC/PNEC = 0.0069 which gives the risk insignificant.
Author: Health and Medical Care Administration, Region Stockholm