Detaljerad miljöinformation

Detailed background information

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 = 0.1149 μg/L

Where:

A = 838.7490 kg (total amount API of benzylpenicillin sodium in Sweden year 2021, data from IQVIA) (Ref. 1)

R = removal rate = 0% (no data available)

P = number of inhabitants in Sweden = 10*10⁶

V (L/day) = volume of waste water per capita and day = 200 (ECHA default) (Ref. 2)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref. 2)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Fresh water green algae (Selenastrum capricornutum) (Ref. 3)

NOEC 3 days (growth inhibition): 100 mg/L (Modified ISO 8692)

Fresh water cyanobacteria (Microcystis aeruginosa) (Ref. 3)

EC₅₀ 7 days (growth inhibition): 6μg/L (Modified ISO 8692)

Respiration inhibition test in aerobic bacteria (Ref. 4)

IC₅₀ 30 min (respiration inhibition): >100 mg/L (OECD 209)

IC₅₀ 20 hours (respiration inhibition): >100 mg/L (OECD 209, prolonged test)

According to the ECHA guideline (Ref. 2) and EMA guideline (Ref. 5) with corresponding Q&A (Ref. 6), cyanobacteria is considered to be the most sensitive species for antibiotics. However, the presented ecotoxicological data from cyanobacteria (Ref. 3) lack information on whether exponential growth is achieved throughout the complete exposure period. Hence this data cannot be used for the calculation of PNEC.

Since there are not sufficient data for the calculation of PNEC, the phrase “Risk of environmental impact of Benzylpenicillin cannot be excluded, since there is not sufficient ecotoxicity data available” is used.

Degradation

Biotic degradation

Ready degradability:

Benzylpenicillin did not pass the criteria for readily biodegradability.

Closed Bottle Test (OECD 301D) resulted in <60% degradation in 28 days (Ref. 7)

Inherent degradability:

Benzylpenicillin did not pass the criteria for inherent biodegradability.

Zahn-Wellens test (OECD 302B) resulted in <70% degradation in 7 days (Ref. 8)

Benzylpenicillin did not pass the criteria for ready biodegradability and inherent biodegradability which justifies the phrase “Benzylpenicillin is potentially persistent”.

Bioaccumulation

An experimentally derived Log K_ow of 1.83 (Ref. 9) indicates that Benzylpenicillin has low potential for bioaccumulation.

Log K_ow<4 which justifies the phrase “Benzylpenicillin has low potential for bioaccumulation”.

Excretion (metabolism)

Within 6 hours approximately 70% of administered dose is excreted as the active form through the urine (Ref. 10).

PBT/vPvB assessment

Since Benzylpenicillin has a low potential to bioaccumulate it does not fulfill the B criteria and is not classified as a PBT/vPvB compound.

References:

1. Data from IQVIA ”Consumption assessment in kg for input to environmental classification v1 - updated 2021 (data 2022)”.

2. ECHA, European Chemicals Agency. Guidance on information requirements and chemical safety assessment. Ver 2.1, 2011.
   http://echa.europa.eu/documents/10162/13643/information_requirements_r2_en.pdf

3. Halling-Sørensen B. Algal toxicity of antibacterial agents used in intensive farming. Chemosphere 2000 v40 p731-739

4. Kümmerer K. et al. Standardized tests fail to assess the effects of antibiotics on environmental bacteria. Water Research 2004 v38 p2011-2016

5. Committee for Medicinal Products for Human Use (CHMP); Guideline on the environmental risk assessment of medicinal products for human use.
   2006 Doc Ref EMEA/CHMP/SWP/4447/00

6. Committee for Medicinal Products for Human Use (CHMP): Q&A on guideline on the environmental risk assessment of medicinal products for human use. 2010 Doc Ref EMA/CHMP/SWP/44609/2010

7. Alexy R., Kümpel T., Kümmerer K. Assessment of degradation of 18 antibiotics in the Closed bottle Test. Chemosphere 2004 v57 p505-512.

8. Bergheim M. et al. Benzylpenicillin transformation in aqueous solution at low temperature under controlled laboratory conditions. Chemosphere 2012 v81(11) p1477-1485

9. Hansch C et al. (1994), ChemID+, US National Library of Medicin, National Institutes of Health, http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp

10. SPC for Benzylpenicillin 2018-06-29 www.fass.se