Detaljerad miljöinformation

Predicted Environmental Concentration (PEC)

PEC is calcluated according to the following formula:

PEC (μg/L) = (A*10⁹*(100))/(365*P*V*D*100) = 1.5*10^-6*A = 0.0004 μg/L

Where:

A = 2.6 kg ipratropium bromide (monohydrate), total sold amount API in Sweden year 2020, data from IQVIA).

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 = 10 (ECHA default) (Ref I)

Predicted No Effect Concentration (PNEC)

Environmental assessment was based on toxicity data; however as only one and not three different trophic levels were available, a valid PNEC cannot be calculated. Therefore, the following phrase is used:

“Risk of environmental impact of ipratropium cannot be excluded, since there is not sufficient ecotoxicity data available”.

Degradation

Ipratropium is not readily biodegradable (CO₂-production test, detailed method unknown, no standard guideline used) (Ref II).

The phrase ”Ipratropium is potentially persistent” is therefore used.

Bioaccumulation

log P = -2.2 at pH 7 (Detailed method unknown, no standard guideline used. log P was estimated via the determination of Ipratropium concentrations in the water and octanol phase, respectively. ) (Ref III)

Justification: As log P is below 4, the phrase “Ipratropium has low potential for bioaccumulation” is used.

Excretion (metabolism)

Following inhalation 10 to 30% of a dose, depending on the formulation and inhalation technique, is generally deposited in the lungs (Ref IV, V, VI, VII, VIII, IX). The portion of the dose deposited in the lungs reaches the circulation rapidly and has a nearly complete systemic availability (Ref X). The major part of the dose is swallowed and passes the gastro-intestinal tract. Due to the negligible gastro-intestinal absorption of Ipratropium bromide the bioavailability of the swallowed dose portion accounts for only ~2% of the dose (Ref X, XI, XII, XIII). The major portion of approximately 60% of the systemic available dose is eliminated by metabolic degradation, probably in the liver (Ref XIV, XV).

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. Boehringer Ingelheim GmbH internal report U91-0792, 1991

3. Boehringer Ingelheim GmbH internal report A082322, 2012

4. Taburet AM, Schmit B. Pharmacokinetic optimisation of asthma treatment. Clin Pharmacokinet 1994;26(5):396-418

5. Short MD, Singh CA, Few JD, Studdy PR, Heaf PJD, Spiro SG. The labelling and monitoring of lung deposition of an inhaled synthetic anticholinergic bronchodilating agent. Chest 1981;80:918-21

6. Timsina MP, Martin GP, Marriott C, Ganderton D, Yianneskis M. Drug delivery to the respiratory tract using dry powder inhalers.Int J Pharm 1994;101(1/2):1-13

7. Chrystyn H. Standards for bioequivalence of inhaled products. Clin Pharmacokinet 1994;26(1):1-6.

8. Dolovich M. Lung dose, distribution, and clinical response to therapeutic aerosols.Aerosol Sci Technol 1993;18(3):230-40.

9. Boehringer Ingelheim GmbH internal report U95-0166, 1995

10. Ensing K, Zeeuw Rd, Nossent GD, Koeter GH, Cornelissen PJG. Pharmacokinetics of ipratropium bromide after single dose inhalation and oral and intravenous administration. Eur J Clin Pharmacol 1989; 36(2):189-94.

11. Boehringer Ingelheim GmbH internal report U86-0434, 1986

12. Boehringer Ingelheim GmbH internal report U92-0550, 1992

13. Boehringer Ingelheim GmbH internal report U96-0020, 1995

14. Adlung J, Hoehle KD, Zeren S, Wahl D. Studies on pharmacokinetics and biotransformation of ipratropium bromide in man. Untersuchungen zur Pharmakokinetik und Biotransformation von Ipratropiumbromid am Menschen. Arzneimittelforschung 1976;26:1005-10.

15. Boehringer Ingelheim GmbH internal report U73-0141, 1973