Detaljerad miljöinformation

Environmental Risk Classification 

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)

PEC = 0.218 μg/L

Where:

A = 1590.225 kg (total sold amount API in Sweden year 2023, data from IQVIA).

R = 0 % 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

No data is available.

Environmental risk classification (PEC/PNEC ratio)

It is not possible to calculate the environmental risk classification (PEC/PNEC ratio) due to lack of data.

Summary phrases for the environmental risk:

Risk of environmental impact of balsalzide cannot be excluded, since no ecotoxicity data are available.

Degradation

Balsalzide is a pro-drug, which is metabolized in the gut to mesalazine, responsible for the anti-inflammatory action, and the inert carrier molecule metabolite.

Ready degradability: Mesalazine showed > 90 % degradation over 28 days.
(Ref II)

Summary phrases for degradation:

The potential for persistence of balsalzide cannot be excluded, due to lack of data.

Bioaccumulation

Partitioning coefficient: 

Balsalazide

LogP = 1.3 (experimental data, pH unknown, method unknown)

LogP = 3.37 (predicted data, pH unknown (source ALOGPS))

LogP = 3.17 (predicted data, pH unknown (source Chemaxon))
(Ref III)

Mesalazine (active metabolite)
LogP = 0.75 (predicted data, pH unknown (source ALOGPS))

LogP = -0.29 (predicted data, pH unknown (source Chemaxon))
(Ref IV)

Justification of chosen bioaccumulation phrase:

Since LogP < 4, balsalazide and its active metabolite have low potential for bioaccumulation.

Excretion (metabolism)

The systemic uptake of balsalazide itself is low (< 1 %) and the major part of the dose is split in the colon by bacterial azoreductase. This cleavage results in the primary metabolites 5-aminosalicylic acid (5-ASA), responsible for the anti-inflammatory action, and 4-aminobenzoyl-beta-alanine (4-ABA), considered to be an inert carrier.

Most of the dose is eliminated via the faeces but about 25 % of the released 5-ASA appears systemically predominantly as the N-acetylated metabolite (NASA) after inactivation in the colonic mucosa and liver. The systemic uptake of 4-ABA is only 10-15 % of that of 5-ASA and also this metabolite is grossly N-acetylated (to NABA) in the first pass.

In urine, virtually only NASA and NABA are recovered and their renal clearances are high.

Protein binding of 5-ASA is about 40 % and that of NASA about 80 %.

Fasting slightly increases the systemic uptake of balsalazide and its metabolites.
(Ref V)

References

1. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment.

2. Summerton L, Sneddon HF, Jones LC, Clark JH. Green and Sustainable Medicinal Chemistry: Methods, Tools and Strategies for the 21st Century Pharmaceutical Industry. 2016.

3. Drug Bank data for balsalzide, retrieved from Drug Bank December 2024.

4. Drug Bank data for mesalazine, retrieved from Drug Bank December 2024.

5. SmPC of Colazide, retrieved from MPA, November 2024.