Detaljerad miljöinformation

Environmental Risk Classification

Total sales of esomeprazole and omeprazole are included in the calculation of the Predicted Environmental Concentration (PEC), as a worst case, as esomeprazole is the S-enantiomer of the racemate omeprazole and the toxicity is assumed to be very similar.

Predicted Environmental Concentration (PEC)

PEC is calculated according to the following formula:

PEC (μg/L) = (A*10⁹*(100-R))/(365*P*V*D*100) = 1.37*10^-6*A(100-R)

Where:

A = total sold amount API in Sweden year 2022, data from IQVIA (Ref I).

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

hydrolysis or biodegradation) = 0 if no data is available .

P = number of inhabitants in Sweden = 10*10⁶

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

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

(Note: The factor 10⁹ converts the quantity used from kg to μg).

A = 8 171.9377 kg. This figure is based on sales figures (286.0346 kg esomeprazole magnesium + 1262.6530 kg esomeprazole magnesiumdihydrate + 63.6454 kg esomeprazole magnesiumtrihydrate + 246.4380 kg esomeprazole sodium + 6239.9573 kg omeprazole 73.2094 kg omeprazolmagnesium)

R = 0

PEC = 1.37 x 10^-6 x 8 171.9377 (100-0) = 1.1196 µg/L

(Note: Whilst esomeprazole and omeprazole are extensively metabolised, little is known about the ecotoxicity of the excreted metabolites. Hence, a total residue approach is taken where no metabolism of parent compound is considered; a worst case assumption.)

Ecotoxicity data - Omeprazole

Endpoint	Species	Common Name	Method	Time	Result	Ref.
EbC50 – Based on Biomass Note 7	Pseudokirchneriella subcapitata (formerly known as Selenastrum capricornutum)	Green Alga	OECD 201	72 h	30.1 mg/L Note 1	III
ErC50 – Based on Growth Rate Note 7					>75.9 mg/L Note 1
NOEC - Based on Biomass Note 7					<1.81 mg/L Note 1
NOEC - Based on Growth Rate Note 7					1.81 mg/L Note 1
EC50 - Based on Immobilisation  Note 7	Daphnia magna	Giant Water Flea	OECD 202	48 h	>100 mg/L Note 3	IV
LC50 Note 7	Danio rerio (formerly known as Brachydanio rerio)	Zebra fish	OECD 203	96 h	41.9 mg/L Note 1	V
NOEC - Based on Activated Sludge Respiration Inhibition Note 8	-	-	OECD 209	3 h	100 mg/L	VI
EC50 - Based on Activated Sludge Respiration Inhibition Note 8					>100 mg/L

_{Note 1: Results are expressed as mean measured concentrations.}

_{Note 2: The population relevant endpoints measured were survival, fecundity and adult length.}

_{Note 3: Concentrations were confirmed by analysis, and results expressed as nominal.}

_{Note 4: The population relevant endpoints measured were total number of emerged adult insects, sex ratio and replicate mean plus individual emergence times (development rates).}

_{Note 5: The population relevant endpoints measured were hatch, survival, length and dry weight.}

_{Note 6: Results are expressed as nominal concentrations.}

_{Note 7: Data from studies on omeprazole sodium.}

_{Note 8: Data from studies on omeprazole.}

PNEC (Predicted No Effect Concentration)

The lowest LC50 value presented in the table above for Omeprazol is 41.9 mg/L (equivalent to 41 900 µg/L) and an assessment factor of 1000 is applied to calculate PNEC for Omeprazol (ref VII).

PNEC =41 900 µg/L /1000 =41.9 µg/L

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 1.1196/41.9= 0.027, i.e. PEC/PNEC ≤ 1 which justifies the phrase “Use of Omeprazol has been considered to result in insignificant environmental risk”.

Environmental Fate Data – Omeprazole

Endpoint	Method	Test Substance Concentration	Time	Result	Ref.
Half-life Note 9	Unknown	In aqueous solution	-	T1/2 @20 oC: pH 4 = 15 mins pH 7 = 30 h pH 9 = > week	VII
				T1/2 =10 h @ 37 oC, pH 7

_{Note 9: This study predates current ERA regulatory requirements and may not have been undertaken to standardised test guidelines.}

Physical Chemistry Data- Omeprazole

Endpoint	Method	Test Substance Conditions	Result	Ref.
Distribution Coefficient Octanol Water	Unknown	-	Log D (experimental) = 2.24	VII
Solubility Water  Note 9	Unknown	22 oC	130 mg/L
Dissociation Constant Note 9	Unknown	-	pKa(1) = 4 (Pyridinium ion)
Dissociation Constant			pKa(2) = 8.8 (Benzimidazole ion)

_{Note 9: This study predates current ERA regulatory requirements and may not have been undertaken to standardised test guidelines.}

Biodegradation

Omeprazole was found not to be readily biodegradable in biodegradability studies. The substance has hence been assigned the phrase: “Omeprazol is potentially persistent”.

In Swedish: ”Omeprazol är potentiellt persistent” under the heading ”Nedbrytning”.

Bioaccumulation

Since Log D < 4, Omeprazole has low potential to bioaccumulate and the phrase “Omeprazole has low potential for bioaccumulation” is assigned (Ref VIII).

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

References

1. Data from IQVIA "Consumption assessment in kg for input to environmental classification v1 - updated 2023 (data 2022)".

2. [ECHA] European Chemicals Agency. Guidance on Information Requirements and Chemical Safety Assessment. Chapter R.16: Environmental exposure assessment (version 3.0). February 2016.

3. H 168/68 Na salt: acute Toxicity to Pseudokirchneriella sucapitata. Document No. T3355, Corning Hazelton, Harrogate, England. June 1996.

4. H 168/68 Na salt: acute Toxicity to Daphnia Magna. Document No. T3353, Corning Hazelton, Harrogate, England. June 1996.

5. H 168/68 Na salt: acute Toxicity to Brachydanio rerio. Document No. T3354, Corning Hazelton, Harrogate, England. June 1996.

6. IVL Swedish Environmental Research Institute Commissioned Report; Investigation of the ‘ready biodegradability’ of A001 drug substance, Report BD3984. June 1991.

7. ECHA (European Chemicals Agency) 2008. Guidance on information requirements and chemical safety assessment. Chapter R.10: Characterisation of dose [concentration]- response for environment

   https://echa.europa.eu/documents/10162/13632/information_requirements_r10_en.pdf/bb902be7-a503-4ab7-9036-d866b8ddce69

8. Hazardous Substances Data Bank (HSDB). Hazardous Substance Data Bank number: 4433.

   http://www.chemspider.com/Chemical-Structure.4433.html