Detaljerad miljöinformation

PEC/PNEC = 0.0037/240 = 0.0000154

PEC/PNEC<< 0.1

EnvironmentalRisk Classification

Predicted Environmental Concentration (PEC)

The PEC is based on following data:

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

PEC (µg/L) = 1.37*10^-6*A*(100-R)

PEC           = 1.37 * 10^-6 * 27.02 * (100 – 0)

                  = 0.0037 µg/L

A (kg/year) = total sold amount API in Sweden year 2021, data from IQVIA

= 27.02 kg/year

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

hydrolysis or biodegradation) = 0 (default as 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.1)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref.1)

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

Metabolism

Terbutaline is metabolised and excreted as the sulphate conjugate with no active metabolites being formed (Ref. 2). Note: Whilst terbutaline is 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 terbutaline.

Ecotoxicity data

Endpoint	Species	Common Name	Method	Time	Result	Ref
ErC10 - Based on Growth Rate	Pseudokirchneriella subcapitata (formerly known as Selenastrum capricornutum)	Green Alga	OECD 201	72 h	300 mg/L  Note 1	3
ErC50 - Based on Growth Rate					>500 mg/L  Note 1
EC50 - Based on Immobilisation	Daphnia magna	Giant Water Flea	OECD 202	48 h	240 mg/L  Note 1
LOEC - Based on Immobilisation					100 mg/L  Note 1
NOEC - Based on Immobilisation					50 mg/L Note 1
EC50 – Based on Mortality	Danio rerio (formerly known as Brachydanio rerio)	Zebra Fish	OECD 203	96 h	>1000 mg/L  Note 1
NOEC - Based on Mortality					1000 mg/L  Note 1

^{Note 1: Results are expressed as nominal concentrations.}

PNEC (Predicted No Effect Concentration)

Short-term tests have been undertaken for species from three trophic levels, based on internationally accepted guidelines. Therefore, the PNEC is based on the acute toxicity (E/LC50) to the giant water flea (Daphnia magna), the most sensitive species, and an assessment factor of 1000 is applied, in accordance with ECHA guidance (Ref. 4).

PNEC = 240000 µg/L / 1000 = 240 µg/L

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0037 μg/L /240 μg/L = 0.0000154

PEC/PNEC << 0.1 which justifies the phrase ”Use of terbutaline sulphate has been considered to result in insignificant environmental risk.”

In Swedish: “Användning av terbutalin har bedömts medföra försumbar risk för miljöpåverkan.”

Environmental Fate Data

Endpoint	Method	Test Substance Concentration	Time	Result	Ref
Percentage DOC Removal	Aerobic biodegradation ISO 7827-1984E	36 mg Carbon/L	28 d	5 %	3

Biodegradation

Terbutaline sulphate is not readily degradable, and since no other biodegradation data is available, the substance has been assigned the phrase “Terbutaline sulphate is potentially persistent”.

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

Physical Chemistry Data

Endpoint	Method	Result	Ref
Dissociation Constant	Not specified	pKa = 8.8	4
		pKa = 10.1
		pKa = 11.2
Water Solubility	Not specified	1g/1.5ml (666.7g/L) Note 2	5
Partition Coefficient Octanol Water		Log P = 0.9 Note 2

Note 2:  The reported Log P is a measured distribution coefficient. 

Bioaccumulation

Since Log P < 4, the phrase “Terbutaline sulphate has low potential for bioaccumulation” is assigned.

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

References

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

   
   

2. Electronic Medicines Compendium, SmPC Bricanyl https://www.medicines.org.uk/emc/(accessed September 2019).

   
   

3. Report No: SR99250-01 3/92. Environmental assessment of the pharmaceutical agent 'A003' from AB Astra. Toxicon. April 1992.
   
   

4. S1.03 Marketing, General Properties, Terbutaline Sulphate Drug Substance, Respiratory Use. AstraZeneca. Doc ID-000329236, Version 3.0.
   
   

5. Drugbank. Terbutaline. https://www.drugbank.ca/drugs/DB00871 Accessed 16/9/2022