The T-value in the score for hazard refers to chronic toxicity. Underlying data for P, B and T are from Fass.
Fass environmental information for Atacand (kandesartan) from AstraZeneca (downloaded 2019-11-07).
Persistence: "Candesartan is potentially persistent" is chosen. For details see the Fass text.
Bioaccumulation: "Since Log P < 4 the phrase ‘Candesartan has low potential for bioaccumulation’ is assigned."
Chronic toxicity: There are data for 3 trophic levels, most sensitive fish (Pimephales promelas) NOEC 1 000 microg/L.
PEC/PNEC is based on sales data in Sweden in year 2016. PEC/PNEC = 0.00145 which gives the risk insignificant.
Comparative assessment of environmental risk when using angiotensin II antagonists candesartan, losartan, valsartan, irbesartan, eprosartan and telmisartan from a Swedish perspective (Report Goodpoint 2019).
Angiotensin receptor blockers are relatively stable and can reach the aquatic environment at concentrations higher than that of many other pharmaceuticals. They are all fat-soluble, suggesting high potential for bioconcentration in biota, which has been documented for irbesartan, since telmisartan does not bioconcentrate in proportion to its very high fat solubility. Bioconcentration data for the other substances are missing. The target is preserved in fish but not invertebrates and algae. However, growth studies (28–32 days) of fish for four of the substances (candesartan, losartan, valsartan, irbesartan) show low toxicity, but mechanism-based efficacy data are completely lacking for all.
Based on the information, none of the angiotensin receptor blockers can be attributed to "high" environmental risk, at the same time irbesartan stands out as a substance with higher risk than the others, based on available data. Sales of irbesartan are low in relation to candesartan and losartan. In 2018, over 18 times more losartan than irbesartan was prescribed and just over 18 times more candesartan than irbesartan in Sweden (in DDD count, excluding combination preparation). Therefore, if irbesartan was substituted for losartan or candesartan, the levels of losartan or candesartan in the environment would probably only increase by about 6% on average and therefore increase the environmental risk for these marginally, but it would eliminate the environmental risk with irbesartan. However, it should be mentioned that the environmental risk is unclear for all substances studied.
Based on concentrations of irbesartan over CEC (critical environmental concentration) in Swedish surface water, as well as bioconcentration in wild fish and a relatively high persistence in wastewater treatment plants and the environment, there is a risk picture that should be further investigated. The reasons for the replacement of irbesartan are moderate at present, and the situation is difficult to assess. An exchange of irbesartan with either losartan or candesartan may be justified, primarily based on the fact that the environmental exposure to losartan or candesartan would increase only marginally.
Author: Health and Medical Care Administration, Region Stockholm