Detaljerad miljöinformation

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 = 0.000794052 µg/L

Where:

A = total actual API sales in Sweden for the most recent year 5.796 kg (total sold amount API in the most recent sales data for Sweden (2022) was distributed by IQVIA in 2023)

R = 0

P = number of inhabitants in Sweden = 10 *10⁶

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

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

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Scenedesmus subspicatus) (guideline e.g. OECD 201) [Reference I]:

EC₅₀ 72 h > 4.9 µg/L

NOEC = 4.9 µg/L (inhibition of growth)

Crustacean (Daphnia magna) (water-flea) (guideline e.g. OECD 211) [Reference II]:

Acute toxicity

Not available.

Chronic toxicity

Water-flea (Daphnia magna) reproduction test

NOEC 21 days = 9.1 µg/L (Survival)

Fish:

Acute toxicity

Not available.

Chronic toxicity

Zebra fish (Brachydanio rerio) early life stage test (guideline e.g. OECD 210) [Reference III]

NOEC 35 days = 10 µg/L

Other ecotoxicity data:

Activated sludge respiration inhibition test (guideline e.g. OECD 209) [Reference IV]

EC₅₀ 3h > 1000 mg/kg

NOEC 3h ≥ 1000 mg/L

Earthworm Acute Toxicity (Eisenia fetida) in a 14-day test (guideline e.g. OECD 207) [Reference VIII]

NOEC 14 days >1000 mg/kg dry soil

Sediment-dwelling larva of Chironomus riparius in a water-sediment system (guideline e.g. OECD 219) [Reference IX]

NOEC 28 days > 20 µg/L

PNEC (µg/L) = lowest NOEC from long-term ecotoxicity/10, where 10 is the assessment factor used. NOEC for algae (4.9 µg/L) has been used for this calculation since it is the most sensitive of the three tested species.

PNEC = 4.9 µg/L/10 = 0.49 µg/L

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC =   0.000794052 µg/L / 0.49 µg/L = 0.0016205 i.e. PEC/PNEC ≤ 0.1

The calculated PEC/PNEC ratio is ≤ 0.1.

Use of Etravirine has been considered to result in insignificant environmental risk.

Degradation

Biotic degradation

Ready degradability:

No data available

Inherent degradability: -

Simulation studies:

Aerobic degradation in aquatic sediment systems

Etravirine was investigated for its aerobic degradation in a 100-day aquatic sediment test, according to OECD 308 [Reference V]. The rates of dissipation (DT₅₀ and DT₉₀) of Etravirine from the water phase were calculated using first order kinetics:

System	Water
	DT50 (Days)	DT90 (Days)
River	0.6	2.0
Pond	1.1	3.6

Etravirine is slowly degraded to form four minor degradation products in an aerobic transformation test in aquatic sediment systems (OECD 308). Consequently, Etravirine is not considered as readily biodegradable. The medicine is considered as potentially persistent.

Conclusion for degradation: Etravirine is potentially persistent.

Abiotic degradation

Hydrolysis: -

Photolysis: -

Bioaccumulation

Partition coefficient octanol/water:

The partition coefficient octanol/water was determined according to OECD 117 log D_ow = 3.4 [Reference VI]

Bioconcentration factor (BCF):

The bioconcentration and depuration characteristics of Etravirine in the rainbow trout (Oncorhynchus mykiss) in a flow through system were examined according to OECD 305. [VII]

BCF_low dose = 370.3

BCF_high dose = 476.9

These BCF values indicate that Etravirine does have low potential for bioaccumulation.

Conclusion for bioaccumulation: Etravirine has low potential for bioaccumulation.

Excretion (metabolism)

-

PBT/vPvB assessment

	PBT-criteria	Results for BDQ
Persistence	Half-life in freshwater: DT50 > 40 days Half-life in sediment: DT50 > 120 days	DT50,river = 0.6 days DT50,system = slowly degraded
Bioaccumulation	BCF > 2000	BCF = 370.3 (low dose) and476.9 (high dose)
Toxicity	Chronic NOEC < 10 µg/L	NOECalgae = 4.9 µg/L NOECdaphnia = 9.1 µg/L NOECfish = 10 µg/L

Conclusion for PBT-assessment:

According to the established EU-criteria Etravirine should not be regarded as a PBT substance.

References

1. Peither A., TMC 125 (R165335): Toxicity to Scenedesmus subspicatus in a 72-Hour Algal Growth Inhibition Test (OECD 201); RCC Ltd Study A59231; JNJ Study RMD771; March 20, 2007.

2. Peither A., TMC 125 (R165335): Effect on Survival and Reproduction of Daphnia Magne in a Semi-Static Test Over Three Weeks (OECD 211); RCC Ltd study A59253; JNJ Study RMD772; March 20, 2007.

3. Peither A., TMC 125 (R165335): Toxic Effects of Zebra Fish (Brachydanio rerio) in an Early-Life Stage Toxicity Test (OECD 210); RCC Ltd study A59275; JNJ Study RMD773; April 19, 2007.

4. Seyfried B., TMC 125 (R165335): Toxicity to activated Sludge in a Respiration Inhibition test (OECD 209); RCC Ltd study A59297; JNJ Study RMD774; December 19, 2006.

5. Völkel W.,  TMC 125 (R165335): Route and Rate of Degradation in aerobic Aquatic Sediment Systems (OECD 308); RCC Ltd study A59365; JNJ Study RMD778; February 15, 2007.

6. Weiseenfeld M., Partition Coefficent (n-octanol/water) of TMC 125 (R165335) RCC study A59308; March 10, 2006.

7. Burri R., Bioconcentration: Flow-Through Fish Test with [³H] –TMC125 in Rainbow Trout (Oncorhynchus mykiss); RCC Ltd Study A59332; JNJ Study RMD777; September 29, 2006.

8. Schmidt T., TMC 125 (R165335): Acute Toxicity of the Earthworm Eisenia fetida in a 14 day test (OECD 207); RCC Study Number B14973; JNJ Study RMD905; July 4, 2007.

9. Memmert U., Effects on the Development of Sediment-Dwelling Larvae of Chironomus riparius in a Water-Sediment System (OECD 219): RCC Study Number B67511: JNJ Study RMD983; August 4, 2008.

10. 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