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Posaconazole

Hazard 5 P 3 B 0 T 2 Risk Insignificant

Information

The T-value in the score for hazard refers to chronic toxicity. Underlying data for P and B are from assessment report for Noxafil (posaconazole). Underlying data for T and risk are from Fass.

Assessment report

Data from the assessment report for Noxafil (posakonazol) 24 Juli 2014 EMA/CHMP/75051/2015 and 20 Februari 2014 EMA/159150/2014.

Hazard

Persistence: "The half-life of the parent posaconazole in two river sediments was calculated to be 20.4 and 21.1 days. The half-lives of the two major transformation products in in two river sediments were calculated to be 38 and 106.7 (metabolite M2) and 358.1 and 108.1 (M3). The Applicant states that the metabolites (M2 and M3) could not be named according to chemical nomenclature as their definitive structures are unknown. However, different half-lives for the fate of the major transformation products (elucidated structure) of posaconazole in water/sediment systems have been calculated. Nevertheless, all three transformation products show persistence in sediment with half-lives >120d. Posaconazole is therefore classified as being persistent."

Bioaccumulation: "The Phase I screening for persistence, bioaccumulation and toxicity (PBT) indicates that further evaluation of posaconazole is not warranted due to a log Kow < 4.5." "Based on the Phase II–Tier A assessment, posaconazole is unlikely to represent a risk to surface water, ground water micro-organisms and sediment dwelling organisms. Posaconazole is not likely to bioconcentrate in aquatic organisms and is not a PBT compound (BCF < 2000), indicating little risk to the aquatic and sediment environments."

Toxicity: No data.

Risk

The risk, PEC/PNEC, from a European perspective:

PEC = 760 microg/kg.

PNEC = 8.06 microg/kg. It is not clear how PNEC has been calculated.

PEC/PNEC = 0.01 which gives the risk insignificant.

Fass environmental information

Below is Hazard and Risk from Fass environmental information for Noxafil (downloaded 2018-09-05).

Hazard

Persistence: "Posaconazole has a half-life less than 32 days.The phrase “Posaconazole is degraded in the environment is thus chosen."

Bioaccumulation: "Posaconazole has a measured bioconcentration factor (BCF) of 20 (OECD 305)."

Chronic toxicity: There is NOEC for 3 trophic levels, lowest NOEC for algae (Selenastrum capricornutum) 41 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2015. PEC/PNEC = 0.00067 which gives the risk insignificant.

Author: Health and Medical Care Administration, Region Stockholm