Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration (PEC)

In order to normalize the different irinotecan varieties on the active ingredient irinotecan, all sales volumes are adjusted to the molecular weight of irinotecan.

Irinotecan variety	Molecular weight (g/mol)	Tonnage conversion factor
Irinotecan	586,68	1
Irinotecan hydrochloride trihydrate	641,2	0,914
Irinotecan sucrosofate	1569,5	0,374

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)

PEC = 0,000727 μg/L

Where:

A = 5,307 kg (total sold amount API in Sweden year 2022, data from IQVIA). Reduction of A may be justified based on metabolism data.

R = X % 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. I)

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

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae S. capricornutum (ref 2 ):

EC₅₀ 96 h (growth rate) = 585 µg/L

Crustacean, water flea (Daphnia magna) (ref 2):

LC₅₀ 48 h (immobilization) = 23 µg/L

Fish, fathead minnow (Pimephales promelas) (ref 2):

LC₅₀ 96 h (mortality) = 3789 µg/L

PNEC (μg/L) = 23 /1000, where 1000 is the assessment factor used. LC₅₀ for Daphnia magna 48h has been used for this calculation since it is the most sensitive of the three tested species.

PNEC = 0,023 µg/L

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0,000745 /0,023 = 0,0316, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase ‘Use of irinotecan has been considered to result in insignificant environmental risk.

Degradation

Environmental Fate Data for Irinotecan (ref. 3):

Property	Predicted average	Unit	Predicted range
Atmos. Hydroxylation Rate	8.13*10-11	cm3/molecule*sec	8.13*10-11
Biodeg. Half-Life	95.9	days	95.9
Fish Biotrans. Half-Life (Km)	1.05	days	1.05
Soil Adsorp. Coeff. (Koc)	2.09*104	L/kg	2.09*104
Bioconcentration Factor	7.19	L/kg	7.19

Abiotic degradation

Hydrolysis (ref 4):

Test results showed that hydrolysis was not a significant process in the first 1h of the reaction under various initial values of pH.

15 % degradation in 2 h at PH 4 and 5

20 % degradation in 24 h at PH 4 and 5

15% degradation in 24 h at PH 8 and 9

Photolysis (ref 4):

The photodegradation of IRI in ultrapure water resulted in more than 90% degradation within 1 h at pH values 7 and 9 and 80% at pH value 6, at lower pH values 4 and 5, approximately 20 and 40% of IRI was degraded within 2 h, respectively

Results indicate that there is significant photolytic degradation of Irinotecan at neutral and basic pH values, but very limited photolytic degradation of irinotecan at pH 4 and 5.

According to the above data, the substance Irionotecan considered to be slowly degraded in the environment.

Bioaccumulation

Bioconcentration factor (BCF):

BCF 7,19 (ref. 3)

Partitioning coefficient: e.g. Log P = 3,94 at pH 7 (ref. 4)

Since BCF < 500 och Log P < 4 at pH 7,

the substance has low potential for bioaccumulation

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. A. Olalla, N. Negreira, M. L_opez de Alda, D. Barcel, Y. Valc_arcel, A case study to identify priority cytostatic contaminants in hospital effluents; Chemosphere 190 (2018) 417-430

3. https://comptox.epa.gov/dashboard/chemical/env-fate-transport/DTXSID1041051

4. https://hmdb.ca/metabolites/HMDB0014900

5. Photolytic and photocatalytic degradation of antineoplastic drug irinotecan. Kinetic study, identification of transformation products and toxicity evaluation; Α. Chatzimpaloglou, C. Christophoridis, I. Fountoulakis, M. Antonopoulou, D. Vlastos, A. Bais, K. Fytianos, Chemical Engineering Journal 405 (2021) 126866