Detaljerad miljöinformation

Physical properties^4,5

Solubility at pH 7: 20 000 µg/L

pKa: 5.3

Vapor pressure: 6.57 x 10^-10 mmHg

Molecular weight: 323.42 Da

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 = 0.0031 μg/L

Where:

A =	34.1 kg (estimated amount API consumption in Sweden year 2027).
R =	34 % removal rate as calculated with SimpleTreat 4.0 using the lowest sludge sorption coefficient (Kd) of 44.5 and elimination rate constant (kbiodeg) of 0.057 per hour (Reference OECD 106 & OECD 314B)
P =	number of inhabitants in Sweden = 10 * 106
V (L/day) =	wastewater volume per capita and day = 200 (ECHA default)1
D =	factor for wastewater dilution by surface water flow = 10 (ECHA default)1

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Activated sludge microorgansims (guideline OECD 209)³

EC₁₅ (respiration inhibition) = >1000 000 μg/L

EC₅₀ (respiration inhibition) = >1000 000 μg/L

Green alga (Raphidocelis subcapitata) (guideline OECD 201)⁶

NOEC 72 h (growth rate&yield, chronic toxicity) = 880 μg/L

EC₅₀ 72 h (growth rate&yield, chronic toxicity) = >880 μg/L

Daphnids (Daphnia magna) (guideline OECD 211)⁷

NOEC 21 days (reproduction&survival, chronic toxicity) = 971 μg/L

LOEC 21 days (reproduction&survival, chronic toxicity) = >971 μg/L

Fathead Minnow (Pimephales promelas) (guideline OECD 210)⁸

NOEC 33 days (early life stage, chronic toxicity) = 922 μg/L

LOEC 33 days (early life stage, chronic toxicity) = >922 μg/L

Based on the lowest NOEC for the species Raphidocelis subcapitata and using the assessment factor² of 10, the PNEC is calculated to 880/10 = 88 µg/L.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0031/88 = 3.5 x 10^-5, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase ”Use of abrocitinib has been considered to result in insignificant environmental risk.”

Adsorption (guideline OECD 106)⁹

Solid	Kd (L/Kg)	Koc (L/Kg)
Activated sludge (Denton)	44.5	140
Activated sludge (Easton)	57.2	156
HOM soil (TB-L-PF)	315	6700
LOM soil (RMN-LS)	850	106 000
HOM sediment (Brandywine creek)	342	7940
LOM sediment (Choptank river)	35.4	8840

HOM = high organic matter, LOM = low organic matter

Degradation

Biotic degradation

Water-sediment transformation simulation (guideline OECD 308)¹⁰

Length of study: 240 days

High organic sediment system: Brandywine creek

Low organic sediment system: Choptank river

Sediment extraction solvent: THF + 1% NH₄OH

Supplemental extraction solvents: Water, hexanol or hexane

The results from the study are shown in the table below.

Data on day 240 at °C	Brandywine Creek		Choptank River
Total system
Half-life (days)	249	79.5
Total 14CO2 (% of AR)	9.1	25.4
% Parent (% of AR)	59.3	12.9
Aerobic Water Layer
Half-life (days)	7.5	20.9
Parent (% of AR)	<2.7	0.1
Sediment Layer
Half-life (days)	ND	77.9
Bound/NER (% of AR)	28.4	25.1
Extractables (% of AR)	63.1	24.6
Parent (% of AR)	56.6	12.8

ND = not detected, NER = non-extractable residues, AR = applied radioactivity

Biodegradation in surface water, sediment-water system (guideline OECD 309)¹¹

Length of study: 28 days

Parent compound remaining at the end of the study: 6.3 %

Total mineralisation: 10.2 %

Non-extractable residue: 57.6 %

Loss of parent DT₅₀: 8.1 days

WWTP degradation (guideline OECD 314B)¹²

Length of study: 28 days

Parent compound remaining at the end of the study: 0.0 %

Total mineralisation: 36.5 %

Non-extractable residue: 19.9 %

Elimination rate k-value: 0.057 per hour

Loss of parent DT₅₀: 0.5 days

Justification of chosen degradation phrase

As the highest total system DT₅₀ value (water-sediment transformation simulation, OECD 308) was calculated to 249 days, it corresponds to the degradation phrase ”abrocitinib is potentially persistent.”

Bioaccumulation

Partitioning coefficient (guideline OECD 107)¹³

pH	Log Dow
5	1.47
7	1.86
9	1.85

Justification of chosen bioaccumulation phrase

Since log D_ow < 4 at pH 7, abrocitinib has low potential for bioaccumulation.

References

1. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment chapter R10.

2. ECHA, European Chemicals Agency. 2008 Guidance on information requirements and chemical safety assessment chapter R10.

3. Study report 260E-320: PF-04965842: An activated sludge, respiration inhibition test. August 2018.

4. Cibinqo Environmental risk assessment. January 2020.

5. June 2020.

6. Study report 260P-113: PF-04965842: A 72-hour toxicity test with the freshwater alga (Raphidocelis subcapitata). January 2019.

7. Study report 260A-266: PF-04965842: A flow-through life-cycle toxicity test with the cladoceran (Daphnia magna). February 2019.

8. Study report 260A-264: PF-04965842: An early life-stage toxicity test with the fathead minnow (Pimephales promelas). June 2019.

9. Study report 260E-316: PF-04965842: Adsorption/desorption characteristics in representative soils, sediments, and activated sludge solids. December 2018.

10. Study report 260E-318: PF-04965842: Aerobic transformation in aquatic sediment systems. March 2020.

11. Study report 260E-319: PF-04965842: Biodegradation in surface water. January 2019.

12. Study report 260E-315: PF-04965842: Biodegradation in activated sludge. May 2019.