Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration

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)

Where:

A (total sold amount of API in Sweden year 2024, information obtained from Lif) = 1,041 kg

R (removal rate) = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)

Default values:

P = number of inhabitants in Sweden = 10 x 10⁶

V (L/day) = volume of wastewater per capita and day = 200 (Ref I)

D = factor for dilution of waste water by surface water flow = 10 (Ref I)

PEC = 0.14 µg/l

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Pseudokirchneriella subcapitata) (Ref II):

EC₅₀ 72 h (growth rate): 30.2 µg/L

EC₁₀ 72 h (growth rate): 24.1 µg/L
NOEC 72 h (growth rate): 17.8 µg/L
Protocol: OECD 201

Crustacean (Daphnia magna) (Ref III):

EC₁₀ 21 d (reproduction): 11200 µg/L

NOEC 21 d (reproduction): 9150 µg/L
Protocol: OECD 211

Fish (Danio Rerio) (Ref IV):

LC₅₀ 96 h (lethality): > 100000 µg/L
NOEC 96 h (lethality): > 100000 µg/L
Protocol: OECD 236

Fish (Danio Rerio) (Ref V):

LC₁₀ 28 days (lethality): 435 µg/L
NOEC 28 days (lethality): 93 µg/L
Protocol: OECD 210

Other ecotoxicity data:

Lowest NOEC = 17.8 µg/L

AF = 10

PNEC = Lowest NOEC/AF = 17.8 µg/L/10 = 1.78 µg/L

The assessment factor (AF) 10 is used, which is the AF used for three long-term ecotoxicity data endpoints. NOEC for Algae (Pseudokirchneriella subcapitata) 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 = 0.14/1.78 = 0,08

Justification of chosen environmental risk phrase:

PEC/PNEC ≤ 0.1 which justifies the phrase "Use of ketoprofen has been considered to result in insignificant environmental risk".

Degradation

Biotic degradation

Ready degradability:

Test showed 0% degradation in 29 days (protocol: ISO9439) (Ref VI)

Justification of chosen degradation phrase:

Ketoprofen fails to pass the ready degradation test according to OECD criteria, which justifies the phrase “Ketoprofen is potentially persistent”

Bioaccumulation

Partition coefficient:

Ketoprofen has low potential for bioaccumulation, as indicated by a log Kow of 1.65 at pH 7 (protocol: OECD 107)

(Ref VII)

Excretion (metabolism)

Around 80% of an administered dose is excreted in the urine, mainly as a glucuronide metabolite (Ref VIII). Ketoprofen metabolites are not active (Ref IX).

References

1. ECHA, European Chemicals Agency, 2008 Guidance on information requirements and chemical safety assessment. https://echa.europa.eu/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment

2. Sanofi Internal report: Ketoprofen: Toxicity to Pseudokirchneriella subcapitata in an Algal Growth Inhibition Test. OECD 201. Report 117651210 , February 2017.

3. Sanofi Internal report: Influence to Daphnia magna in a Semi-Static Reproduction Test. OECD 211. Report 117651221, March 2017.

4. Sanofi internal report: Acute Toxicity to Zebrafish (Danio rerio) Embryos in a 96-hour Static Test. OECD 236. Report 117651238, February 2017

5. Sanofi internal report: Ketoprofen: Toxicity to Zebrafish (Danio rerio) in an Early-Life Stage Test. OECD 210. Report 135531232, January 2019.

6. Internal report: Ketoprofen, Biodegradability test (1993)

7. Internal report: Ketoprofen, Octanol-water partition coefficient determination (1993)

8. Miles S., 2007, Ketoprofen, xPharm: The Comprehensive Pharmacology Reference, p1-7

9. Williams R.L. and Upton R.A., 1988, The Clinical Pharmacology of Ketoprofen, The Journal of Clinical Pharmacology, 28 (issue supplement S1), p S13-S22