Detaljerad miljöinformation

1. PREDICTED ENVIRONMENTAL CONCENTRATION (PEC):

The Predicted Environmental Concentration is calculated according to the following formula:

PEC (µg/L) = A x 10⁹ x (100-R) / 365 x P x V x D x 100

Where:
A (kg/year)	=	9.04202054 kg (total sold amount API in the most recent sales data for Sweden (2019) was distributed by IQVIA/LIF in 2020)
R (%)	=	removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)
	=	0% (worst-case scenario: no removal)
P	=	number of inhabitants in Sweden (9 x 106)
V (L/day)	=	volume of waste water per capita and day
	=	200 (ECHA default) [6]
D	=	factor for dilution of waste water by surface water flow
	=	10 (ECHA default) [6]
PEC (µg/L)	=	0.001376259 µg/L

2. PREDICTED NO EFFECT CONCENTRATION (PNEC)

2.1. Ecotoxicological studies

2.1.1. Algae

Green algae (Pseudokirchneriella subcapitata) (OECD 201) [1]:

E_bC₅₀ (biomass) 72 h = 7.6 mg/L

NOEC_b (biomass) = 1.6 mg/L

E_rC₅₀ 72 h (growth rate) = 15.1 mg/L

NOEC_r (growth rate) = 5.0 mg/L

2.1.2. Crustacean

Acute

Water-flea (Daphnia magna) (OECD 202) [2]:

EC₅₀ 48 h (immobilization) = 12.3 mg fentanyl HCl/L ≈ 11.1 mg fentanyl/L

Chronic

Not available

2.1.3. Fish

Acute

Zebra fish (Brachydanio rerio) (OECD 203) [3]:

LC₅₀ 96 h (Survival) = 24.0 mg/L

NOEC (Survival) = 5.0 mg/L

Chronic

Not available

2.1.4. Other ecotoxicity data

Activated sludge respiration inhibition test Microorganisms (OECD 209) [4]:

EC₅₀ 3 h > 80 mg/L

NOEC ≥ 80 mg/L

2.2. Calculation of Predicted No Effect Concentration (PNEC)

PNEC (µg/L) = lowest EC50/1000, where 1000 is the assessment factor used. EC50 for Daphnia magna 11.1 mg/L has been used for this calculation since it is the most sensitive of the three tested species. As for the algae species, the growth rate endpoint has been chosen in favor of that of the algae biomass in the determination of the PNEC. According to the OECD 201 guideline, preference should be given to the growth rate endpoint.

PNEC = 11.1 mg/L/1000 = 11.1 µg/L

2.3. Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.001376259/11.1 = 0.000123987 i.e. PEC/PNEC ≤ 0.1

Since PEC/PNEC ≤ 0.1, Fentanyl has been considered to result in insignificant environmental risk.

Conclusion for environmental risk:

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

3. DEGRADATION

3.1. Biotic degradation

3.1.1. Ready biodegradation

Fentanyl is not readily biodegradable in a biodegradability test according to OECD No. 301 F: “Manometric respirometry test”. [5]

Within the given test period of 28 days and at the given test conditions fentanyl HCl cannot be regards as readily biodegradable. Consequently, the medicine is potentially persistent.

Conclusion for degradation:

Fentanyl is potentially persistent.

4. BIOACCUMULATION

4.1 Partition coefficient octanol/water

The partition coefficient octanol/water was to be log K_ow = 3.94 (pH = 3) using unknown internal method. The ChemSpider ACD/Percepta log Kow for Fentanyl = 3.89. The substance therefore has low potential for bioaccumulation. [7]

Conclusion for bioaccumulation:

Fentanyl has low potential for bioaccumulation.

5. PBT-ASSESSMENT

	PBT-criteria	Results for Fentanyl
P	DT50 freshwater > 40 days or DT50 sediment > 120 days	-
B	BCF > 2000	-
T	Chronic NOEC < 0.01 mg/L or CMR or endocrine disrupting	NOECalgae = 5 mg/L NOECfish = 5 mg/L

The PBT-criteria are not fulfilled. Therefore, Fentanyl is not considered a PBT-substance.

6. REFERENCES

1. Memmert U., Fentanyl – Toxicity to Pseudokirchneriella subcapitata (formerly Selanastrum capricornutum) in a 72-Hour Algal Growth Inhibition Test; RCC Ltd Study A46877; Janssen Study RMD725; Jan 17, 2008.

2. Van Woensel M., Baelen S., Vos E., The Acute Toxicity of Fentanyl.HCL R133119 in the water-flea Daphnia magna. Janssen Study ADKD1 /009. April 20, 1998.

3. Memmert U., Acute Toxicity to Zebra Fish (Brachydanio rerio) in a 96-hour static test; RCC Study Number A46890; Janssen Study RMD726; January 17, 2008.

4. Memmert U., Fentanyl – Toxicity to Activated Sludge in a Respiration Inhibition Test; RCC Study Number a46912; Janssen Study RMD727; January 17, 2008.

5. Vos E., Van Baelen S., Woensel M., The Biodegradability of Fentanyl.HCL Manometric Respirometry Test; Janssen Study BDAS/0075. March 24, 1998.

6. 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

7. Fentanyl, ChemSpider, ID # 3228, July 7, 2015, http://www.chemspider.com/Chemical-Structure.3228.html?rid=a50892f0-2f7f-4572-8e41-d979e2af623f