Amoxicillin

Ecotoxicological Summary

Hazard for aquatic organisms

Freshwater

Hazard assessment conclusion:

PNEC aqua (freshwater)

PNEC value:

0 mg/L

Assessment factor:

10

Extrapolation method:

assessment factor

PNEC freshwater (intermittent releases):

0 mg/L

Marine water

Hazard assessment conclusion:

PNEC aqua (marine water)

PNEC value:

0 mg/L

Assessment factor:

100

Extrapolation method:

assessment factor

STP

Hazard assessment conclusion:

PNEC STP

PNEC value:

10 mg/L

Assessment factor:

100

Extrapolation method:

assessment factor

Sediment (freshwater)

Hazard assessment conclusion:

PNEC sediment (freshwater)

PNEC value:

0.001 mg/kg sediment dw

Extrapolation method:

equilibrium partitioning method

Sediment (marine water)

Hazard assessment conclusion:

PNEC sediment (marine water)

PNEC value:

0 mg/kg sediment dw

Hazard for air

Air

Hazard assessment conclusion:

no hazard identified

Hazard for terrestrial organisms

Soil

Hazard assessment conclusion:

PNEC soil

PNEC value:

0 mg/kg soil dw

Extrapolation method:

equilibrium partitioning method

Hazard for predators

Secondary poisoning

Hazard assessment conclusion:

no potential for bioaccumulation

Additional information

According to ECHA’s Guidance on information requirements and chemical safety assessment. Chapter R.10: Characterisation of dose [concentration]-response for environment, PNEC for freshwater are estimated by division of the lowest value for the toxicity with the relevant assessment factor.

As stated in the Guidance, blue-green algae should be counted among the primary producers due to their autotrophic nutrition. Moreover, according to the European Medicines Evaluation Agency (EMEA), the use of blue-green algae (Cyanophyta) is recommended for effect assessment of antimicrobials, as they are more sensitive indicator organisms than green algae (EMEA, 2006).

Only short-term aquatic toxicity data on fish and daphnia are available for amoxicillin. The algal growth inhibition test is, in principle, a multi-generation test. However, for purposes of applying the appropriate assessment factors, the EC50 is treated as a short-term toxicity value. Nevertheless, from the toxicity data found in the literature, it could be realized that algae have a higher sensitivity toward amoxicillin compared to crustaceans and fish. Although no long-term toxicity studies to aquatic invertebrates or fish were available in the literature, taking into account the acute toxicity studies performed on crustaceans and fish, amoxicillin seems to be not toxic for these two trophic levels. In regards to aquatic algae, amoxicillin displayed toxicity to the cyanobacterium but showed no toxicity to the green algae. The results indicated that the prokaryotic blue-green algae are considered more sensitive to antibiotics than eukaryotic green algae, most probably due to their structure being more like bacteria.

Taking this information into account, the starting point for PNEC derivation was determined to be the study conducted by Andreozzi et al. (2004) were the 96h-NOEC for S. leopoliensis was determined to be 0.78 µg/mL (worst case scenario). The assessment factor to be applied would be 10 for freshwater and 100 for marine water and intermediate releases, since no effects are expected neither in fish nor aquatic invertebrates in long-term studies.

Conclusion on classification

Based on available data, amoxicillin only shows toxic effects to cyanobacteria most problably due to their structure being more like bacteria (prokaryotic cells). No effects were observed in fish, aquatic invertebrates nor green algae or plants.

According to the Guidance on the Application of the CLP Criteria (Version 4.1 - June 201), where the algal toxicity EC50 falls more than 100 times below the next most sensitive species and results in a classification based solely on this effects, consideration should be given to whether this toxicity is representative of the toxicity to aquatic plants. The obtained data suggest that the use of a single species for assessing the toxicity effects of antibiotics is not realistic and therefore, the substance would not be classified for aquatic toxicity according to CLP Regulation (EC) no. 1272/2008.