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 = 0.0012 μg/L

Where:

A = 9 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):

Algal growth (OECD 201)

EC₅₀ 96 h (growth rate) = 100 mg/L (Ref. III)

NOEC = 10 mg/L

Crustacean, water flea (Daphnia magna):

Chronic toxicity (OECD 211)

NOEC 21 day (reproduction) > 100 mg/L (Ref. IV)

Fish, zebrafish (Brachydanio rerio):

Early life-stage toxicity (OECD 210)

NOEC 30 day (growth) > 100 mg/L (Ref. V)

PNEC = 1 mg/L = 1000 μg/L (10 mg/L / 10 based on the most sensitive chronic NOEC for algae with an assessment factor (AF) of 10)

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0012/1000 = 1.2E-06 , i.e. PEC/PNEC ≤ 0.1 which justifies the phrase "Use of sugammadex has been considered to result in insignificant environmental risk."

Biotic Degradation

Sediment Transformation (OECD 308) (Ref. VI)

Two sediments varying in pH, textural characteristics, organic matter content and microbial content with associated overlying waters, were tested. The sediment samples were extracted using acetonitrile:water and acetonitrile:phosphoric acid followed by rotary evaporation for extract concentration. In addition, for one replicate of each sediment, a humic/fulvic acid and humin fractionation was performed to characterize bound residues.

The results indicated a half-life = 4.5 to 13.5 days in total water-sediment systems. The majority of the degradation observed was due to transformation. Some mineralization occurred (5.8 – 8.4%) and bound residues accounted for 10 – 61% of the applied radioactivity at 100 days. At the end of the study (day 100), 11 – 13% parent compound was detected in the system. In one sediment-water system, no metabolites >10% were found, but in the other system, 3 metabolites >10% were found.

Justification of chosen degradation phrase:

The DT₅₀ < 32 days justifies the phrase “Sugammadex is degraded in the environment.”

Bioaccumulation

Partitioning coefficient (OECD 107) (Ref. VII)

Measured log K_ow = -6.4

Justification of chosen bioaccumulation phrase:

The log K_ow < 4 justifies the phrase “Sugammadex 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. M Bogers, 2005. "Fresh water algal growth inhibition test with Org 25969 (limit). NOTOX Project 442057, ‘s-Hertogenbosch, Netherlands, 25 October 2005.

4. Michielsen, 2008. "Daphnia magna, reproduction test with Org 25969 (semi-static). NOTOX Project 488486, ‘s-Hertogenbosch, Netherlands, 23 June 2008.

5. M Bogers, 2005. "Fish early-life stage toxicity test with Org 25969 (semi-static). NOTOX Project 442079, ‘s-Hertogenbosch, Netherlands, 28 November 2005.

6. B van Noorloos, 2007. Aerobic degradation of 14C-Org 25969 in two water/sediment systems. NOTOX Project 442046, 26 January 2007.

7. MJC Brekelmans, 2005. "Determination of the partition coefficient (N-octanol/water) of Org 25969", NOTOX Project 442024, ‘s-Hertogenbosch, Netherlands, 3 October 2005.