Detaljerad miljöinformation

Predicted Environmental Concentration (PEC)

PEC is calculated according to the following formula:

PEC (µg/L) = (A*10⁹*(100-R))/(365*P*V*D*100) = 1.52*10^-4*A = 0.0206 µg/L

Where:

A = 135,75 kg (total sold API in Sweden year 2016, data from QuintilesIMS)

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 = 9*10⁶

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

D = factor for dilution of waste = 10 (ECHA default) (Ref I)

Predicted No Effect concentration (PNEC)

Ecotoxicological studies

Green alga (Scenedesmus subspicatus) (OECD 201) (Ref II):

No concentrations above the solubility of the test item in the test medium (1.43 mg/L) were tested.

EC₅₀ 72 h (growth inhibition) > 1.43 mg/L

NOEC 72 h (growth inhibition) = 1.43 mg/L

Water-flea (Daphnia magna) (OECD 202) (Ref III):

No concentrations above the solubility of the test item in the test medium (1.93 mg/L) were tested.

EC₅₀ 48 h (immobilization) > 1.93 mg/L

NOEC 48 h (immobilization) = 1.93 mg/L

Zebra fish (Danio rerio) (OECD 203) (Ref IV):

No concentrations above the solubility of the test item in the test medium (1.63 mg/L) were tested.

LC₅₀ 96 h > 1.63 mg/L

NOEC 96 h (endpoint: mortality and signs of intoxication) = 1.63 mg/L

Conclusion: In the acute effect studies with alga, water-flea and fish, no effects on the test organisms were observed up to the highest test concentrations. In order to be able to calculate a PEC/PNEC ratio, the concentration of 1.43 mg/L and an assessment factor of 1000 are used for calculation of the PNEC.

PNEC = 1.43 mg/L / 1000 = 0.00143 mg/L = 1.43 µg/L

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0206 / 1.43 = 0.014

Justification: PEC/PNEC ≤ 0,1 which justifies the phrase “Use of bisacodyl has been considered to result in insignificant environmental risk”.

Degradation

Bisacodyl is not readily biodegradable:

Tests have shown 11% degradation in 28 days (OECD 301) (Ref V). The percentage biodegradation did not exceed 60 % within a 10 day window. Bisacodyl can therefore be considered to be not readily biodegradable.

Bioaccumulation

The partition coefficient (n-octanol/water) was experimentally determined (OECD 117) (Ref VI):

log D = 2.5

Justification: log D < 4 which justifies the phrase “Bisacodyl has low potential for bioaccumulation”.

Adsorption

After administration in humans, bisacodyl is hydrolyzed to bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM) which is the active moiety.

BHMP has no high tendency for adsorption (OECD 121) (Ref VII):

Koc = 88

Excretion (metabolism)

Bisacodyl is a pro-drug. After administration in humans bisacodyl is hydrolyzed to bis-(p-hydroxyphenyl)-pyridyl-2-methane (BHPM) which is the active moiety. BHMP is mainly excreted as monoglucuronide (Ref VIII).

References:

1. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment. Chapter R.10: Characterization of dose [concentration]-response for environment.

   http://echa.europa.eu/documents/10162/13632/information_requirements_r10_en.pdf

2. Boehringer Ingelheim GmbH internal report U02-1644, 2002

3. Boehringer Ingelheim GmbH internal report U02-1645,2002

4. Boehringer Ingelheim GmbH internal report U03-1253, 2003

5. Boehringer Ingelheim GmbH internal report U02-1606, 2002

6. Boehringer Ingelheim GmbH internal report U02-1605, 2002

7. Boehringer Ingelheim GmbH internal report U06-0257, 2006

8. Arzneimittelforschung, Nov. 1975, 25(11): 1796-1800