Amoxicillin

Endpoint summary

Additional information

Hydrolysis:

Amoxicillin is rapidly hydrolysed under mild acidic and basic conditions (Erah et al., 1997; Barschi et al. 2014) by the opening of the ß-lactam ring through the attack of the nucleophile H2O (Andreozzi et al., 2004) and it is not expected to persist in the environment. Amoxicillin penicilloic acid was proposed as the first degradation product obtained from the hydrolyzation of β-lactam ring with further transformation into amoxicillin penicilloic acid and amoxicillin 2',5'-diketopiperazine (Golza et al., 2013 and Pérez-Parada et al. 2011). The substance could be also susceptible of photoinduced transformation (Andreozzi et al., 2004) into amoxicillin-Soxides (Gozlan et al., 2010).

Biodegradation:

The substance is determined to be not readily biodegradable according to the OECD Guideline 301 criteria, obtaining a 5% of biodegradation based on oxygen consumption (Alexy et al., 2004). Nevertheless, the primary elimination (HPLC) reached 100% within 14 days, most probably due to the abiotic hydrolysis without oxygen consumption (Längin et al., 2009; Alexy et al. 2009). Nevertheless, amoxicillin showed ultimate biodegradation in several studies, reaching 75% of DOC elimination, i.e. inherent biodegradability, was found in a Zahn-Wellens test according to OECD Guideline 302B (Längin et al., 2009). The authors pointed out that after a fast and completed hydrolysis within 4 days, this is further biodegraded to compound B by a loss of the phenol moiety and that compound B is only mineralized further through biotic means. In the same way, Gartiser et al. (2006) found out certain ultimate biodegradation and amoxicillin was regarded as partially biodegradable with formation of stable metabolites, with a 28 days DOC elimination of 30, 90 and 39% (3 replicates) with a lag phase of 14 days. In contrast, no “lagphase” was observed by Andreozzi et al. (2004) in a non-preacclimated sludge.

Degradation products:

In a publication by Gozlan et al. (2013), the formation of degradation products in aqueous solutions containing 100 μg/mL of amoxicillin trihydrate was studied at pH 5, 7 and 8 for 3, 6 and 16 days. The identified degradation products were amoxicillin penicilloic acid, amoxicillin penilloic acid, phenol hydroxypyrazine and amoxicillin 2',5'-diketopiperazine. In another study conducted by Pérez-Parata et al. (2010), the identification of the main transformation products of amoxicillin in wastewater and river water (500 µg/mL) at pH 2, 7, 8 and 10 under dark conditions for 10 days. Amoxicillin was observed to spontaneously and faste degrade under both acidic and alkaline conditions. Nevertheless, the profile of degradation products depended on the selected media, time and temperature. Both amoxicillin diketopiperacine-2’,5’ and amoxilloic acid diastereomers were identified as main transformation products related to hydrolysis which involves the opening of the β-lactam ring. Besides, another amoxicillin transformation product formed during analysis was also structurally elucidated for the first time (amoxicilloic acid methyl ester) via accurate mass measurements. According to the authors, due to the pH adjustment, the opening of the β-lactam ring with further arrangement of the molecute to give amoxicilloic acid methyl ester would be another pathway to be considered. Furthermore, Pereira et al. (2014) observed that amoxicillin removal was concomitant with the accumulation of transformation product, which were putatively identified as stereoisomers of amoxicilloic acid during the study of solar photocatalytic oxidation of recalcitrant natural metabolic by products of amoxicillin biodegradation. On the other hand, Hirsch et al. (1999) investigated sewage treatment plant effluents and surface water samples from agricultural areas in Germany and concluded that penicillins could not be determined in the aquatic environment due to chemically unstable β-lactam ring.

Bioaccumulation:

The substance amoxicillin has an octanol-water partitioning coefficient (log Kow) of 0.87 (Sangstar, 1994) and an estimated Log Kow factor of 0.97 (EPI-Suite EPA (USA), BCFBAF v3.01). Thus, it is of low bioaccumulation potential. Moreover, the estimated bioaccumulation factor for the test item was 3.162 L/kg wet-wt (EPI-Suite, KOCWIN v2.00.).

Adsorption:

The substance amoxicillin has an octanol-water partitioning coefficient (log Kow) of 0.87 (Sangstar, 1994) and an estimated Log Kow factor of 0.97 (EPI-Suite EPA (USA), BCFBAF v3.01). Thus, it is of low adsorption potential. The calculated Koc is 108.4 L/kg and log Koc is 2.035 ( EPI Suite, KOCWIN v2.00, MCI method).

In the study by Andreozzi et al. (2004), where adsorption to active sludge was analysed, no “lag phase” was observed, also in the presence of non-preacclimatated sludge. This is probably due to the structural similarity between amoxicillin and other natural substances. From obtained results it is evident that both biodegradation and adsorption processes can play an important role in

the transformation and removal of amoxicillin from the aquatic environment, the former being the faster one. Kbio = 4.43 x 10-1 h-1. Moreover, Githingi et al. (2004) stated that amoxicillin decreased in sorption with pH increase. The sorption behaviour can be explained by their carboxylic acid and amine functional groups, giving them amphoteric properties. At high pH, the carboxylic group dissociates creating net negative charges on the molecules. At low pH, the amine group take up hydrogen atoms leading to a net positive charge.