Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration (PEC)

Currently, ciprofloxacin is marketed in Sweden as ciprofloxacin hydrochloride monohydrate, ciprofloxacin hydrogen sulphate, and ciprofloxacin as such. Ciprofloxacin is the active pharmaceutical ingredient (API) and marketed volumes need to be adjusted to this moiety for PEC calculation.

Ciprofloxacin varieties	Molecular weight	Conversion factor	Sale volume (2022)	API amount (2022)
Ciprofloxacin	331.4 g/Mol	1.00	22.51	22.51
Ciprofloxacin hypochlorite monohydrate	385.82 g/Mol	0.86	2696.18	2318.71
Ciprofloxacin hydrogen sulphate	428.47 g/Mol	0.77	6.93	5.34
Total sale volume API				2346.56

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) = 0.32 μg/L

Where:

A = 2346.56 kg (total sold amount API in Sweden year 2022, data from IQVIA / LIF)

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) (Reference I)

D = factor for dilution of wastewater by surface water flow = 10 (ECHA default) (Reference I)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies*

Algae (green algae, Anabaena flos-aquae):

EC₁₀ 72 hours (growth rate) = 1.4 μg/L, E_rC₅₀ 71 hours (growth rate) = 2.3 μg/L. Guideline OECD 201. (Reference II)

Crustacean (waterflea, Daphnia magna):

Chronic toxicity

EC₁₀ 21 days (reproduction) = 10.9 μg/L. Guideline OECD 211. (Reference III)

Fish (fathead minnow, Pimephales promelas):

Chronic toxicity

NOEC 29 days (development, survival, length) = 0.89 μg/L. Guideline OECD 210. (Reference IV)

The PNEC was calculated by division of the lowest effect level (NOEC) of the most sensitive taxonomic group considering an appropriate assessment factor (AF). The most sensitive taxonomic group were fish and the lowest effect level was reported as NOEC = 0.89 µg/L. The regulatory default standard AF of 10 was used, which is applicable when there are chronic aquatic toxicity studies representing the three trophic levels (algae, crustaceans, and fish).

PNEC = 0.89 µg/L / 10 = 0.089 µg/L

Environmental risk classification (PEC/PNEC ratio)

The risk quotient PEC/PNEC was calculated with 0.32 µg/L / 0.089 µg/L = 3.61

Justification of chosen environmental risk phrase:

A risk quotient between 1 and 10 qualifies for the phrase “Use of ciprofloxacin has been considered to result in moderate environmental risk.”.

Degradation

Biotic degradation

Ready degradability:

The study reported 0 % biodegradation of ciprofloxacin in 28 days, i.e., the substance is not readily biodegradable. Guideline OECD 301. (Reference V)

Abiotic degradation

Hydrolysis:

This study reported that ciprofloxacin was stable at pH 4, 7, and 9 at 50 °C. Guideline OECD 111. (Reference VI)

Justification of chosen degradation phrase:

Ciprofloxacin is not readily biodegradable and resistant to hydrolysis, which qualifies for the phrase “Ciprofloxacin is potentially persistent.”.

Bioaccumulation

Partitioning coefficient:

The log D_ow was reported as 1.1 at pH 2.5 (< 1 at pH 5.5-7). Guideline OECD 121. (Reference VII)

Justification of chosen bioaccumulation phrase:

As the log D_ow was < 4 ciprofloxacin is not considered bioaccumulative which qualifies for the phrase “Ciprofloxacin has low potential for bioaccumulation.”.

References

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

2. Growth inhibition test with Anabaena flos-aquae under static conditions. Experimental Toxicology, Schering AG, study no. T7078912EXT, report no. PH-36164 (2010).

3. Reproduction study of Ciprofloxacin (BAY q3939) in Daphnia magna. Investigational Toxicology, Bayer AG, study no. TOXT3082931, report no. A51126 (2016).

4. Early-life-stage test with Ciprofloxacin hydrochloride (BAY O009867) on the fathead minnow (Pimephales promelas). Investigational Toxicology, Bayer AG, study no. T101899-8, report no. PH-39261 (2016).

5. Study on the biodegradability of Ciprofloxacin (BAY q3939) in the manometric respiration test. Bayer Pharma AG, study no. TOXT2080392, report no. A47373 (2011).

6. Ciprofloxacin / BAY Q003939 / Report on Physicochemical Properties / Rate of Hydrolysis. Bayer Pharma AG, study no. 09100278, report no. A49381 (2010).

7. BAY O9867: Determination of the (n-octanol/water) by the shake-flask method. Bayer Pharma AG, study no. T102119-5, report no. R-11097.