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 = 0.023 μg/L

Where:

A = 168 kg (total sold amount API in Sweden year 2022, data from IQVIA (Ref I.)

R = 0 % removal rate (worst case assumption)

P = number of inhabitants in Sweden = 10 *10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Ref. II)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Ref. II)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae (Selenastrum capricornutum) (FDA 4.01) (Ref. III):

EC₅₀ 12 day (growth rate) > 0.026 mg/L

NOEC 12 day (growth rate) = 0.026 mg/L

No effects seen up to highest concentration tested

Crustacean, water flea (Daphnia magna) (FDA 4.08) (Ref. IV)

Acute toxicity

EC₅₀ 48 h (mortality) =1.1 mg/L

Chronic toxicity (OECD 211) (Ref. V)

NOEC 21 day (survival) = 0.16 mg/L

Fish, fathead minnow (Pimephales promelas) (OECD 210) (Ref. VI)

Chronic toxicity

NOEC 33 day (growth) = 0.07 mg/L

Fish, bluegill sunfish (Lepomis macrochirus) (FDA 4.11) (Ref. VII)

Acute toxicity

LC₅₀ 96 h (mortality) = 0.85 mg/L

PNEC = 2.6 µg/L (0.026 mg/L / 10) based on the chronic NOEC for the algae and an assessment factor (AF) of 10)

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.023/2.6 = 0.0088, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase "Use of efavirenz has been considered to result in insignificant environmental risk."

Degradation

Biotic degradation

Biodegradation Simulation Screening (FDA 3.11) (Ref. VIII)

Test results showed 12% biodegradation to CO₂ by Day 28

Abiotic degradation

Photolysis (EPA 795.70) (Ref. IX)

Test results indicate 85% photo-degradation over 16 days

Justification of chosen degradation phrase:

Efavirenz is degradable in biological systems and via photolysis, however the criteria for classification as degradable was not met. The phrase “Efavirenz is potentially persistent” is thus chosen.

Bioaccumulation

Bioconcentration Factor (OECD 305). (Ref. X)

Measured BCF values were 439 for low concentration (0.9 µg/L) and 454 for high concentration (9 µg/L)

Justification of chosen bioaccumulation phrase:

Since measured BCF < 500, the substance has low potential for bioaccumulation.

References

1. Data from IQVIA ”Consumption assessment in kg for input to environmental classification - updated 2023 (data 2022)”.

   
   

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

   http://guidance.echa.europa.eu/docs/guidance_document/information_requirements_en.htm
   

3. Springborn Laboratories, Inc. 1997. "DMP 266 - Toxicity to the Freshwater Green Alga," Report No. 97-4-6954, Wareham, MA, 02 October 1997.

   
   

4. Springborn Laboratories, Inc. 1997. "DMP 266 - Acute Toxicity to Daphnids (Daphnia magna) Under Static Conditions," Report No. 97-3-6906, Wareham, MA, 02 October 1997.

   
   

5. Springborn Smithers Laboratories, Inc. 2007. "Efavirenz (DMP 266) - Full Life-Cycle Toxicity Test with Water Flea, Daphnia magna, Under Static-Renewal Conditions," Study No. 12534.6301, Wareham, MA, 09 March 2007.

   
   

6. Springborn Smithers Laboratories, Inc. 2007. "Efavirenz (DMP 266) - Early Life-Stage Toxicity Test with Fathead minnow (Pimephales promelas), Following OECD Guideling #210," Study No. 12534.6302, Wareham, MA, 08 February 2007.

   
   

7. Springborn Laboratories, Inc. 1997. "DMP 266 - Acute Toxicity to Bluegill Sunfish (Lepomis macrochirus) Under Static-Renewal Conditions," Report No. 97-3-6907, Wareham, MA, 02 October 1997.

   
   

8. Springborn Laboratories, Inc. 1997. "DMP 266 - Determination of Aerobic Biodegradation in Water," Report No. 97-4-6937, Wareham, MA, 15 September 1997.

   
   

9. Springborn Laboratories, Inc. 1997. "DMP 266 - Indirect Photolysis Screening Test with Synthetic Humic Water Following EPA/TSCA, 40 CFR Ch. 1, 795.70," Report No. 97-6-7017, Wareham, MA, 25 August 1997.

   
   

10. Springborn Smithers Laboratories, Inc. 2008. "Efavirenz (DMP 266) - Flow-Through Bioconcentration and Metabolism Study with Bluegill Sunfish (Lepomis macrochirus), Following OECD Guideline 305," Study No. 12534.6306, Wareha