Detaljerad miljöinformation

PEC = 0.19 µg/L

There is not sufficient ecotoxicity data to calculate PNEC.

Environmental risk classification

The PEC is based on the following data:

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

PEC (µg/L) = 1.5*10^-6*A*(100-R)

A (kg/year) = total sold amount API in Sweden year 2017, data from IQVIA (former IMS Health and Quintiles).

R (%) = removal rate (due to loss by adsorption to sludge particles, by volatilisation, hydrolysis or biodegradation) = 0 if no data is available.

P = number of inhabitants in Sweden =9*10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref.1).

D = factor for dilution of waste water by surface water flow = 10 (EHCA default) (Ref.1). (Note: The factor 10⁹ converts the quantity used from kg to μg).

A = 1284.4 kg

R= 0

PEC = 1.5 * 10^-6 *1284.4 *(100-0) = 0.19 µg/L

(Note: Whilst isosorbide mononitrate is extensively metabolised in humans, little is known about the ecotoxicity of the metabolites. Hence, as a worst case, for the purpose of this calculation, it is assumed that 100% of excreted metabolites have the same ecotoxicity as parent isosorbide mononitrate).

Metabolism

Elimination takes place by denitration and conjugation. The metabolites are excreted mainly via the kidneys. Only about 2% of the dose is excreted as unchanged drug via the kidneys (Ref.2).

^{Note 1: Concentrations were confirmed by analysis, and results expressed as nominal.}

PNEC (Predicted No Effect Concentration)

Since no long term effect data are available, and only short term data from one species, the water flea, is available, it is not possible to calculate the PNEC (Ref 1). Therefore, the statement "Risk of environmental impact of isosorbide mononitrate cannot be excluded, since there is not sufficient ecotoxicity data available" is used.

In Swedish: ”Risk för miljöpåverkan av isosorbidmononitrat kan inte uteslutas då det inte finns tillräckliga ekotoxikologiska data” under the heading "Miljörisk".

Environmental Fate Data

^{Note 2: This study predates current ERA regulatory requirements and may not have been undertaken to standardised test requirements.}

_{Note 3: The reported Log P is a measured distribution coefficient. For ionisable compounds other AstraZeneca reports often refer to Log D or Log Dow rather than Log P or Log Pow.}

Biotic degradation

No information is available concerning the biodegradability of isosorbide mononitrate, thus the phrase "The potential for persistence of isosorbide mononitrate cannot be excluded, due to lack of data" is assigned.

In Swedish: ”Det kan inte uteslutas att Isosorbidmononitrat är persistent då data saknas” under the heading ”Nedbrytning”.

Bioaccumulation

Since log P < 4 at pH 7, the substance has been assigned the phrase: "Isosorbide mononitrate has low potential for bioaccumulation".

In Swedish: ”Isosorbidmononitrat har låg potential att bioackumuleras” under the heading ”Bioackumulering”.

Physical Chemistry Data

References

1. ECHA, European Chemicals Agency. 2008. Guidance on information requirements and chemical safety assessment.

http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm

2. Imdur CDS, Doc ID-001016029 vs 3. February 2005.

3. Isosorbide-5-Mononitrate: Acute toxicity to Daphnia magna. Brixham Environmental Laboratory, AstraZeneca, UK report BL8037/B. March 2005.

4. SDS: Isosorbide-5-mononitrate. Nov 1992 Edition 4. Nobel Chemicals Ltd.

5. LOGKOW Databank. Sangster J. Sangster Res. Lab. Montreal, Quebec, Canada 1994

(M.S. Roberts, P.A. Cossum, E.A. Kowaluk and A.E. Polack, "Factors affecting the availability of organic nitrates from plastic infusion systems: structure of organic nitrate, nature of plastic and effect of temperature", Int. J. Pharm. 17(2-3), 145-159(1983).)