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)

PEC (μg/L) = 1.37*10^-6*A (100-R)

PEC = 1.37*10^-6*0.1312 (100-R)

= 0,0000179744 μg/L

Where:

A = 0.1312 kg (total sold amount API cangrelor sodium in Sweden year 2021, data from IQVIA). Reduction of A may be justified based on metabolism data.

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) = 0 if no data is available. (If R not= 0 this should be justified under the degradation section)

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)

On the basis of the above result, since the PEC value is below 0.01 μg/L it may be assumed that the product is unlikely to represent a risk for the environment following its prescribed usage in patients.

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies*

NA

Environmental risk classification (PEC/PNEC ratio)

NA

Degradation*

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

Biotic degradation

NA

Abiotic degradation

NA

Bioaccumulation

The log_KOW for cangrelor at environmentally relevant pH is less than 0, therefore, it is not considered to bioaccumulate in the enviroment, in accordance with REACH guidance.

Partitioning coefficient:

Log Octanol/Water Partition Coefficient (Log Kow): Log Kow values for Cangrelor tetrasodium have been determined using the shake-flask method at low pH

pH	LogKow
0	-0.43 ± 0.01
1	-0.91 ± 0.04
2	-2.22 ± 0.02

Above pH 2, the compound is highly ionized and therefore extremely hydrophilic. Thus, it is beyond the limits of quantification. At neutral pH 7, the compound exists as the tetra-anion and at this pH the log D has been estimated to be < -16. Since log D_ow < 4 at pH 7, the substance has low potential for bioaccumulation. (Ref. 2)

Excretion (metabolism)

Cangrelor is a substituted nucleotide that is rapidly inactivated by dephosphorylation to the nucleoside. Human metabolites produced and eliminated following administration of cangrelor are structurally related to the purine compounds, adenine and adenosine which are ubiquitous compounds in the environment.

References

I. 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

II. ERA module from the Kengrexal MAA dossier