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) = 1.37*10^-6 * 307.5 * 100 = 0.421 μg/L

Where:

A = 307.4617 kg moxifloxacin hydrochloride (total sold amount API in Sweden year 2021, 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) (ECHA 2008)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (ECHA 2008)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Cyanobacteria (Anabaena flos-aquae) (OECD201):

NOEC 72 hours = 0.0018 mg/L

EC₁₀ 72 hours = 0.003 mg/L

(Data from Bayer; retrieved from iPiE Sum database: T5078910EXT)

Crustacean (Daphnia magna): no data available

Fish: fathead minnow (Pimephales promelas)

Chronic toxicity

NOEC 28 days (hatchability, mortality and weight) = 224.1 μg/L (OECD 210) (Data from Bayer; retrieved from iPiE Sum database: TOXT9080399)

Other ecotoxicity data:

Bacterial respiration inhibition (activated sludge microorganisms)

EC₅₀ 3 h = 68 mg/L (OECD209), (Data from Bayer; retrieved from iPiE Sum database: TOXT0080426)

Sediment-dwelling organisms (Chironomus riparius, non-biting midge)

NOEC 28 days ≥ 100.0 mg/kg dry weight (OECD 218) (Data from Bayer; retrieved from iPiE Sum database: T5081628EXT)

PNEC derivation:

For antibiotics, there is strong evidence that cyanobacteria are the most sensitive species among the usual test set of algae/cyanobacteria, a crustacea species and a fish species. Therefore, a PNEC can be derived from the available cyanobacteria NOEC applying an assessment factor of 10.

PNEC = 1.8 µg/L / 10 = 0.180 µg/L

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0421 µg/L / 0.180 µg/L = 0.233 i.e. PEC/PNEC ≤1 which justifies the phrase "Use of moxifloxacin has been considered to result in low environmental risk."

Degradation

Biotic degradation

Ready degradability: no data available

Simulation studies:

DT50 water:  0.3 - 0.6 days

(Data from Bayer; retrieved from iPiE Sum database: TOXT3079926)

Justification of chosen degradation phrase:

The available data is not sufficient to conclude on the persistence potential. Therefore, the following phrase is used: "The potential for persistence of moxifloxacin cannot be excluded, due to lack of data."

Bioaccumulation

Partitioning coefficient:

logK_ow = -1.87 (method unknown) (SDS Pharmacopeia)

Justification of chosen bioaccumulation phrase:

As the logK_ow remains below the trigger level for a bioaccumlative substance (logK_ow < 4.0), the following statement is used for moxifloxacin: "Moxifloxacin has low potential for bioaccumulation."

Excretion (metabolism)

Moxifloxacin is eliminated in urine and by biliary excretion and metabolism.

Approximately 45% of an oral or IV dose of the drug is excreted unchanged (20% in urine and 25% in feces).1 A total of 96% of an oral dose is excreted as unchanged drug or metabolites. (AHFS Drug Information, 2017)

PBT/vPvB assessment

Based on screening information, moxifloxacin cannot be considered a potential PBT substance as the octanol-water partition coefficient remains significantly below the trigger level for a bioaccumulative substance.

References

• ECHA 2008, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment. http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm

• BAY 12-8039: Growth inhibition test with Anabaena flos-aquae under static conditions.

BAYER - Bayer Pharma AG, T5078910EXT, 2010

• Early-life-stage test with moxifloxacin (Bay 12-8039) on the fathead minnow (Pimephales promelas). BAYER - Bayer Pharma AG, TOXT9080399, 2010

• Respiration inhibition test of moxifloxacin (BAY 12-8039) on activated sludge microorganisms. BAYER - Bayer Pharma AG, TOXT0080426, 2009

• Chronic toxicity test with midge larvae (Chironomus riparius) in a water/sediment system.

BAYER - Bayer Pharma AG, T5081628EXT, 2011

• Aquatic-sediment Study (Aerobic) with Moxifloxacin (BAY 12-8039). BAYER - Bayer Pharma AG, TOXT3079926, 2010

• US Pharmacopeia_186826-86-8_Moxifloxacin Hydrochloride_5003759_SDS_EN_20130626.

AHFS Drug Information, 2017. Pharmaceutical Press.

https://www.medicinescomplete.com/mc/ahfs/current/a300002.htm#pkin