Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration (PEC)

PEC is calculated according to the following formula:

PEC (μg/L) = (A*10⁹*(100-R))/(365*P*V*D*100) = 1.5*10^-6*A*(100-R)

PEC = 8.27*10^-4 μg/L

Where:

A = 5.51 kg (total sold amount API in Sweden year 2020, data from IQVIA).

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)

P = number of inhabitants in Sweden = 10*10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref I)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref I)

Predicted No Effect Concentration (PNEC)

No ecotoxicological study results are available, hence the PNEC (μg/L) could not be estimated.

Environmental Risk Classification (PEC/PNEC ratio)

The PEC/PNEC ratio could not be calculated due to lack of data and

therefore justifies the phrase: "Risk of environmental impact of midazolam cannot be excluded, since no ecotoxicity data are available"

However, according to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of midazolam is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) is below the action limit 0.01 μg/L.

Degradation

No degradation data are available, hence justifies the phrase: "The potential for persistence of midazolam cannot be excluded, due to lack of data"

Bioaccumulation

Partitioning coefficient:

Log P_ow = 4.33 at physiological pH (estimated by unknown method) (Ref II)

Justification for bioaccumulation phrase:

Since log P_ow ≥ 4 at pH 7, midazolam has high potential for bioaccumulation.

Excretion (metabolism)

Midazolam is excreted in urine to less than 1 % as parent compound. The main metabolite is glucuronidated alpha-hydroxymidazolam. The pharmacological activity of the metabolites is not known. (Ref III)

References

1. ECHA, European Chemicals Agency, 2008 Guidance on information requirements and chemical safety assessment. https://echa.europa.eu/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment

2. Hansch C et al. (1995), ChemID+, US National Library of Medicin, National Institutes of Health. https://chem.nlm.nih.gov/chemidplus/

3. Midazolam Panpharma, Summary of Product Characteristics (2021-04-28)