Detaljerad miljöinformation

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 = 0.064 μg/L

Where:

A = 467.74 kg (total sold amount API in Sweden year 2022, data from IQVIA). Total volume of Abacavir = 24.16 Kg. Total volume of Abacavir sulphate = 340.28 Kg. Total volume of Abacavir hydrochloride monohydrate = 103.30 Kg. Total abacavir = 24.16 + 340.28 + 103.30 = 467.74.

.

R = 0% removal rate (conservatively, it has been assumed there is no loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)

P = number of inhabitants in Sweden = 10*10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Reference 1)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Reference 1)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae (Selenastrum caprocornutum):

IC50 72h (growth) = 57,400 μg/L (OECD 201) (Reference 8)

NOEC = 30,000 μg/L

Water flea (Daphnia magna):

Acute toxicity

EC50 48 h (immobility) = 139,000 μg/L (OECD 202) (Reference 3)

NOEC = 79,000 μg/L

Water flea (Ceriodaphnia dubia):

Chronic toxicity

EC50 7 days (reproduction) = 10,000 μg/L (EPA 1002) (Reference 11)

NOEC = 5,600 μg/L

Fathead Minnow (Juvenilee Pimephales promelas):

Acute toxicity

LC50 96 h (lethality) > 95,000 μg/L (OECD 203) (Reference 9)

NOEC = 95,000 μg/L

Chronic Toxicity

NOEC 32 days (mortality) = 10,000 μg/L (OECD 210) (Reference 12)

Other ecotoxicity data:

Microorganisms in activated sludge

EC50 3 hours (Inhibition) > 71,400 μg/L (OECD 209) (Reference 7)

Chironomid (Chironomus riparius)

NOEC 28 days (reproduction) = 100,000 μg/kg (OECD 218) (Reference 14)

PNEC = 5,600/10 = 560 μg/L

PNEC (μg/L) = lowest NOEC/10, where 10 is the assessment factor applied for three long-term NOECs. NOEC for water flea (= 5,600 ug/L) has been used for this calculation since it is the most sensitive of the three tested species.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.064/560 = 1.00 x 10^-4, i.e. PEC/PNEC ≤ 1 which justifies the phrase “Use of abacavir has been considered to result in insignificant environmental risk.”

Degradation

Biotic degradation

Ready degradability:

27% degradation in 28 days (OECD 301B) (Reference 5)

Inherent degradability:

100% primary (loss of parent) degradation in 14 days (OECD 302B) (Reference 10)

Data on the evaluation of degradation products is not available and therefore loss of parent API does not inform summary degradation phrase.

Simulation studies:

Water-sediment study:

50% (DT₅₀ parent) degradation in 9.10 – 15.0 days (OECD 308) (Reference 13)

Data on the evaluation of degradation products is not available and therefore loss of parent API in the OECD 308 is not used to assign a classification.

Non-extractable residue = 37.80% - 62.60%

Abiotic degradation

Hydrolysis:

Half-life, pH 7 > 1 year (TAD 3.09) (Reference 4)

Photolysis:

No Data

Justification of chosen degradation phrase:

Abacavir is not readily biodegradable nor inherently biodegradable. The phrase “Abacavir is potentially persistent” is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log Dow = 1.20 at pH 7 (OECD 107) (Reference 3)

Log Dow at pH 5 = 0.90

Log Dow at pH 7 = 1.20

Log Dow at pH 9 = 1.20

Justification of chosen bioaccumulation phrase:

Since log Pow < 4, the substance has low potential for bioaccumulation.

Excretion (metabolism)

Abacavir is primarily metabolised by the liver with approximately 2% of the administered dose being renally excreted, as unchanged compound. The primary pathways of metabolism in man are by alcohol dehydrogenase and by glucuronidation to produce the 5'-carboxylic acid and 5'-glucuronide which account for about 66% of the administered dose. The metabolites are excreted in the urine.

The mean half-life of abacavir is about 1.5 hours. Following multiple oral doses of abacavir 300 mg twice a day there is no significant accumulation of abacavir. Elimination of abacavir is via hepatic metabolism with subsequent excretion of metabolites primarily in the urine. The metabolites and unchanged abacavir account for about 83% of the administered abacavir dose in the urine. The remainder is eliminated in the faeces (Reference 2).

Please, also see Safety data sheets on http://www.msds-gsk.com/ExtMSDSlist.asp.

References

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

2. Pharmacokinetic properties: Metabolism and Elimination. Summary of Product Characteristics Ziagen (Abacavir) 300mg Film Coated Tablets. ViiV Healthcare UK Ltd., March 2013.

3. Sydney P. 1592U89: Determination of the Physico-Chemical Properties. Report No. 96/GLX179/1022. Huntingdon Life Sciences Ltd, October 1997.

4. Sydney P. 1592U89: Determination of Hydrolysis as a Function of pH. Report No. 96/GLX181/0864. Huntingdon Life Sciences Ltd, October 1997.

5. Jenkins WR. 1592U89: Activated Sludge – Respiration Inhibition Test. Report No. GLX180/970062. Huntingdon Life Sciences Ltd, September 1997.

6. Jenkins CA. 1592U89: Acute Toxicity to Daphnia magna. Report No. 96/GLX180/1068. Huntingdon Life Sciences Ltd, September 1997.

7. Jenkins WR. 1592U89: Biotic Degradation with a Composite Innoculum. Modified Sturm Test. Report No. GLX183/970063. Huntingdon Life Sciences Ltd, September 1997.

8. Swarbrick RH. Abacavir sulphate: Toxicity to Green alga Selenastrum capricornutum. Report No. BL7702/B. Brixham Environmental Laboratory, October 2004.

9. Warbrick RH. Abacavir sulphate: Acute Toxicity to Rainbow trout Oncorhynchus mykiss. Report No. BL7703/B. Brixham Environmental Laboratory, October 2004.

10. Swarbrick RH and Smyth DV. Abacavir sulphate: Determination of Inherent Biodegradability (Zahn-Wellens Test). Report No. BL7704/B. Brixham Environmental Laboratory, March 2006.

11. Young BE and Kent SJ. Abacavir sulphate: Determination of the 3-brood (7 day) Chronic Toxicity of Ceriodaphnia dubia. Report No. BL8144/B. Brixham Environmental Laboratories, March 2006.

12. Ablitt, S. Abacavir hemisulphate:Fish, Early Life Stage Toxicity. Report No. 41500228. Envigo Research Limited, October 2015.

13. Unsworth, R and Carter, J. Abacavir hemisulphate: Aerobic Transformation in Aquatic Sediment Systems. Report No. TMR0047. Envigo Research Limited, November 2016.

14. Ablitt, S. Abacavir hemisulphate: Sediment-Water Chironomid Toxicity Test Using Spiked Sediment. Report No. VG43JK. Envigo Research Limited, February 2017.