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) = 1.5*10^-6*A*(100-R)

PEC = 1.41 * 10^-3 µg/l

Where:
A = 9.42 kg (total sold amount API in Sweden 2020, data from IQVIA)
R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)
P = number of inhabitants in Sweden = 10*10⁶ 
V (l/day) = volume of wastewater per capita and day = 200 (Ref II)
D = factor of dilution of waste water by surface water flow = 10 (Ref II)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Chronic toxicity

Algae (Pseudokirchneriella subcapitata):

NOEC 3 days (growth inhibition) = 100 000 µg/l

(Protocol: OECD 201)

(Ref I)

Crustacean (Daphnia magna):

NOEC 21 days (reduction in reproduction) = 100 000 µg/l

(Protocol: OECD 211)

(Ref I)

Fish (Pimephales promelas):

NOEC 35 days (lethality and developmental effect) = 10 000 µg/l

(Protocol: OECD 210)

(Ref I)

Other ecotoxicity data:

PNEC = 1 000 µg/l

(The PNEC (μg/l) = 10 000/10 using results from the most sensitive chronic toxicity endpoint and an assessment factor of 10 (”long-term results from at least three species representing three trophic levels,” [Ref II, Table R.10-4]). The most sensitive species was the fish, Pimephales promelas  for which the NOEC used was 10 000 μg/l.)

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 1.41 * 10^-3/1 000 = 1.41 *10^-6, i.e. PEC/PNEC ≤ 0.1. Results show that the use of brivaracetam most likely results in insignificant environmental risk. However, since this is a theoretical value the standard environmental phrase to be used is: “Use of brivaracetam has been considered to result in insignificant environmental risk”

Degradation

Biotic degradation

Ready degradability: brivaracetam showed < 60 % degradation over 10 days (protocol: OECD 301B) (Ref I)

Brivaracetam did not pass the ready degradation test and since there is no information available on grade of mineralisation the phrase: ”brivaracetam is potentially persistent.” should be used.

Bioaccumulation

Partitioning coefficient

 Log P_ow = 1.5  at pH 7 (Protocol: OECD 117) (Ref I)

Justification for chosen bioaccumulation phrase: 

Since log P_ow < 4 at pH 7, the substance has low potential for bioaccumulation.

Excretion (Metabolism)

Brivaracetam is excreted 5-10 % as parent compound and 3 major metabolites have been identified. The metabolites are pharmacologically inactive. (Ref I)

References

1. Briviact Assessment report EMA/CHMP/822086/2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/003898/WC500200208.pdf

2. ECHA, European Chemicals Agency. Guidance on information requirements and chemical safety assessment, version 3.0 Feb 2016.