Detaljerad miljöinformation

Detailed background information

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 = 1.79*10^-2 μg/L

Where:

A = 130.3998 kg (total sold amount API in Sweden year 2021, 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)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae:

No data

Water flea (Daphnia magna):

Acute toxicity

EC50 48 h (immobility) = 3.50 μg/L (OECD 202) (Reference 3)

Water flea (Ceriodaphnia dubia):

Chronic toxicity

NOEC 8 days (reproduction) = 0.083 μg/L (USEPA 1002) (Reference 9)

Fish

Acute toxicity

No data

Chronic toxicity

No data

Other ecotoxicity data:

Microbial Inhibition Concentration (Reference 5)

MIC > 11 μg/l, Aspergillus flavus

MIC > 11 μg/l, Azotobacter chroococcum

MIC > 11 μg/l, Chaetomium globosum

MIC > 11 μg/l, Nostoc sp.

MIC > 11 μg/l, Pseudomonas acidovorans

Earthworm (Eisenia foetida):

NOEC 14 days (lethality) = 1000 mg/kg (OECD 207) (Reference 4)

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

Environmental risk classification (PEC/PNEC ratio)

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

Degradation

Biotic degradation

Ready degradability:

No data

Inherent degradability:

No Data

Soil Metabolism:

50% degradation in < 1 day (OECD 307) (Reference 6)

Abiotic degradation

Hydrolysis:

No data

Photolysis:

50 % degradation in 2.63 h (TAD3.10). (Reference 8)

STP Removal

Soil-sediment Sorption log Koc = 4.15 – 4.58 (Reference 7)

Atovaquone is predicted to strongly sorb to organic matrices such as soil, sediment and sludge. Therefore, this substance is likely to be significantly removed from the aquatic environment via sorption to sludge solids. It is anticipated that atovaquone will reach the terrestrial environment via the spreading of sludge solids on agricultural land. EUSES (SimpleTreat) modelling predicts that 78.40% of this substance will distribute to sludge (Reference 3). This is consistent with ADME observation that 94% of the drug substance dose is found in faeces (Reference 2) and not urine. Approximately, 21% of atovaquone will enter the aquatic environment where significant binding to water sediments is expected.

Justification of chosen degradation phrase:

Atovaquone is rapidly degraded in soil, the compartment to which it is likely to partition. For the terrestrial compartment the phrase ‘atovaquone is degraded in the environment’ is appropriate. However, for the aquatic compartment the phrase “The potential for persistence of Atovaquone cannot be excluded, due to lack of data” is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log Kow = 5.31 at pH 7 (TAD 3.02). (Reference 10)

Justification of chosen bioaccumulation phrase:

Since log Kow > 4 at pH 7, the substance has a high potential for bioaccumulation.

Excretion (metabolism)

Greater than 94% of the dose was recovered as unchanged atovaquone in the feces over 21 days. There was little or no excretion of atovaquone in the urine (less than 0.6%). There is indirect evidence that atovaquone may undergo limited metabolism; however, a specific metabolite has not been identified. (Reference 2)

PBT/vPvB assessment

The appropriate degradation data are not available to assign PBT/vPvB criteria.

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. Product Information Mepron. Prescribing information GlaxoSmithKline, Research Triangle Park, NC, May 2008.

   
   

3. http://www.rivm.nl/rvs/Risicobeoordeling/Modellen_voor_risicobeoordeling/EUSES

   
   

4. Sewell IG and Bartlett AJ. 566C80: Acute Toxicity to Daphnia magna. Report No. 303/786. Safepharm Laboratories Limited, June 1997.

   
   

5. Wetton PM. Atovaquone: Acute Toxicity to Earthworms (Eisenia foetida). Report No. 1127/299. Safepharm Laboratories Limited, July 2004.

   
   

6. Hopkins BT. Microbial Inhibition with 566C80. Report No. 40173. ABC Laboratories Limited, September 1992.

   
   

7. Roulstone P and Mckenzie J. Atovaquone: Aerobic Biodegradation in Soil. Report No. 1127/302. Safepharm Laboratories Limited, November 2004.

   
   

8. Gorman M and Abney BS. Soil-Sediment Adsorption-Desorption of 566C80. Report No. 40174. ABC Laboratories Limited, September 1992.

   
   

9. Gorman M and Pratt M. Determination of the Aqueous Photodegradatio of 14C 566C80. Report No. 40175. ABC Laboratories Limited, September 1992.

   
   

10. Goodband TJ and Mullee DM. Atovaquone: Daphnid, Ceriodaphnia Dubia Survival and Reproduction Test. Report No. 1127/1774. Harlan Laboratories Limited, September 2010.

    
    

11. Material Safety Data Sheet for Malarone® Tablets. SDS number 123528. GlaxoSmithKline plc, July 2008.