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 = 1.14 x 10^-4 μg/L

Where:

A = 0.83 kg (total sold amount API in Sweden year 2023, data from IQVIA).

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)

According to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of zidovudine is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) at the time of registration was below the action limit 0.01 μg/L.

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae:

No data

Water flea (Daphnia magna):

Acute toxicity

EC50 48 h (immobility) > 1,000,000 μg/L (OECD 202) (Reference 6)

NOEC > 1,000,000 μg/L

Water flea (Daphnia magna):

Chronic toxicity

EC50 21 days (reproduction) > 100,000 μg/L (OECD 211) (Reference 7)

NOEC = 16,000 μg/L

Rainbow Trout:

Acute toxicity

No data

Other ecotoxicity data:

EC50 3 hours (Inhibition) =102,000 μg/L (OECD 209) (Reference 5)

PNEC cannot be calculated because data is not available for all three (algae, crustacean and fish) of the short-term toxicity endpoints.

Environmental risk classification (PEC/PNEC ratio)

Risk of environmental impact of zidovudine cannot be excluded, since there is not sufficient ecotoxicity data available.

Degradation

Biotic degradation

Ready degradability:

0.23% degradation in 28 days (OECD 301B) (Reference 3)

Inherent degradability:

0% degradation in 28 days (OECD 302B) (Reference 4)

50% primary (loss of parent) degradation in 3 days

Abiotic degradation

Hydrolysis:

Half-life, pH 7 > 1 year (OECD 111) (Reference 7)

Photolysis:

No data

Justification of chosen degradation phrase:

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

Bioaccumulation

Partitioning coefficient:

Log Kow = 0.06 (TAD 3.02) (Reference 7)

Justification of chosen bioaccumulation phrase:

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

Excretion (metabolism)

Zidovudine is primarily eliminated by hepatic conjugation to an inactive glucoronidated metabolite. The 5'-glucuronide of zidovudine is the major metabolite in both plasma and urine, accounting for approximately 50-80% of the administered dose eliminated by renal excretion. 3'-amino-3'-deoxythymidine (AMT) has been identified as a metabolite of zidovudine following intravenous dosing. Renal clearance of zidovudine greatly exceeds creatinine clearance, indicating that significant tubular secretion takes place. (Reference 2)

Please, also see Safety data sheets onhttp://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 Retrovir (Zidovudine) 100mg Capsules. ViiV Healthcare, May 2013.

3. Gorman M. Aerobic Biodegradaion in Water using C14 Zidovudine. Report No. 41035. ABC Laboratories Limited, April 1994.

4. Ziegenfuss S. Zidovudine (GR63367X): Aerobic Biodegradation in Activated Sludge. Report No. ERL-2001-024. GlaxoSmithKline Environmental Laboratory, February 2002.

5. Koper CM. Acute Toxicity of GR63367X (Zidovudine) to Activated Sludge Microorganisms. PEET-2001-066. GlaxoSmithKline Environmental Laboratory, February 2002.

6. Ziegenfuss MC. Toxicity of GR63367X (Zidovudine) to Daphnia magna. PEET-2002-001. GlaxoSmithKline Environmental Laboratory, January 2002.

7. Material Safety Data Sheet for Retrovir (Zidovudine) Tablets. SDS number 127089. ViiV Healthcare plc, April 2011.