Pentanedioic acid, compd. with (1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol (1:1)

Endpoint summary

Additional information

Apart from the Key hydrolysis study (White & Mullee), all studies were carried out on one of the analogue materials. The analogues are considered to be sufficiently similar to the substance of interest (please see attached data matrix and justification in Section 13 for additional details) for them to be used for the purposes of health and environment risk assessments.

Hydrolysis:

(White & Mullee - 2007) The stusy concluded that the reference material (Abacavir Glutarate) had an estimated half-life at 25°C as follows:

pH 4: Approximately > 1 year

pH 7: > 1 year

pH 9: > 1 year

An additional hydrolysis study (Sydney - 1997) concluded that the analogue material (Abacavir Succinate) is hydrolytically stable under acidic, neutral and basic conditions.

Biodegradation:

Two studies have been carried out to assess the analogue materials Abacavir Succinate and Abacavir Hemisulphate for biodegradation in water:

Abacavir Succinate

Jenkins (1996):

Degradation of the test material was slow but progressive throughout the test; the mean cumulative CO₂production was equivalent to 27% of the TCO₂(range 25 to 29%) after 28 days.

The test material cannot therefore be considered to be ultimately degradable. The results of HPLC analysis at the end of the test suggests that the parent molecule may have been subject to primary degradation the extent of which ranged from 41% to 94%.

Abacavir Hemisulphate

Swarbrick & Smyth (2004): Analysis of the biotic exposure at the end of the 14 day test period showed mean degradation of equal to or >99%.

A study has been carried out to assess the analogue material Abacavir Succinate for biodegradation in soil:

Abacavir succinate did not readily undergo aerobic biodegradation in any of the soils examined with 15.3%, 16.8% and 11.4% of the applied test material recovered as carbon dioxide in the clay loam, sandy loam and sandy silt loam soils respectively. Adsorption/desorption: For the following reasons, no determination was possible by Method C19 of Commission Directive 2001/59/EC (which constitutes Annex V of Council Directive 67/548/EEC). The method guideline states that the measurement of adsorption coefficient should be carried out on substances in their ionised and unionised forms. The test material is a salt and is made up of two components, abacavir and glutaric acid. The abacavir component has predicted dissociation constants of 14.86, 6.53 and -3.38 using ACD/pKa 8.03. The glutaric acid component has an experimental database match for dissociation constants of 5.50 and 4.39 using ACD/pKa DB 8.02. Based on this information, this suggests that the abacavir component would be unionised between approximately 7.5 and 13.5. The glutaric acid component is unionised below approximately 3.5. As the pH of sewage treatment plants operate between pH 5.5 and 7.5 and the environmentally relevant range is between approximately 5.5 and 8.5, testing is usually conducted in the latter range. However, the test material is a salt containing amine groups. Experience has shown that positively charged nitrogens can interact with the column stationary phase by forces other than partitioning.