Detaljerad miljöinformation

Environmental Risk Classification

Predicted Environmental Concentration (PEC)

For PEC calculation, the sales volume of acoramidis HCl was re-calculated for the active pharmaceutical ingredient acoramidis. The molecular weight of acoramidis HCl is 328.76 g/mol, that of acoramidis is 292.31 g/mol, which calculates as a ratio of 292.31 / 328.76 g/mol = 0.89. The sales volume of acoramidis HCl in Sweden in 2025 of 1.31 kg was re-calculated to be 1.31 kg * 0.89 = 1.17 kg acoramidis.

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) = 0.000160 μg/L

Where:

A = 1.17 kg (total sold amount API in Sweden in year 2025; data from Bayer AG as for the new drug product there is not yet IQVIA / LIF data)

R = 0 % removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation) = 0 if no data is available

P = number of inhabitants in Sweden = 10 *10⁶

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

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

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies*

Algae (green algae, Raphidocelis subcapitata):

EC₁₀ 72 hours (growth rate) = 26 mg/L, E_rC₅₀ 72 hours (growth rate) >57 mg/L. Guideline OECD 201. (Reference II)

Crustacean (waterflea, Daphnia magna):

Chronic toxicity

EC₁₀ 21 days (mortality, reproduction, body length) >9.1 mg/L. Guideline OECD 211. (Reference III)

Fish (fathead minnow, Pimephales promelas):

Chronic toxicity

EC₁₀/LC₁₀ 33 days (number hatched, post-hatch survival, total length, wet weight) >10 mg/L. Guideline OECD 210. (Reference IV)

Other ecotoxicity data

Activated sludge, respiration inhibition

NOEC 3 hours (activated sludge) = 320 mg/L. Guideline OECD 209. (Reference V)

The PNEC was calculated by division of the lowest effect level (EC₁₀/LC₁₀) of the most sensitive taxonomic group considering an appropriate assessment factor (AF). The most sensitive taxonomic group were algae and the lowest effect level was reported to be EC₁₀ = 26 mg/L. The regulatory default standard AF of 10 was used, which is applicable when there are chronic aquatic toxicity studies representing the three trophic levels (algae, crustaceans, and fish).

PNEC = 26 mg/L / 10 = 2.6 mg/L = 2,600 µg/L

Environmental risk classification (PEC/PNEC ratio)

The risk quotient PEC/PNEC was calculated with 0.000160 µg/L / 2,600 µg/L = 6.88x10^-8

Justification of chosen environmental risk phrase:

A risk quotient of ≤ 0.1 qualifies for the phrase “Use of acoramidis HCl has been considered to result in insignificant environmental risk.”

Degradation

Biotic degradation

Ready degradability:

Activated sludge was exposed to acoramidis HCl at 10 mg/L for 28 days and degradation was measured as carbon dioxide evolution by means of inorganic carbon analysis. The study reported 0 % biodegradation of acoramidis HCl after 28 days. Guideline OECD 301B. (Reference VI)

Simulation studies:

The fate of acoramidis HCl has been studied in two natural aquatic sediment systems under laboratory conditions. The sediment from Lumsdale Middle Pond was a sand with low organic carbon content while that from Calwich Abbey Lake was a neutral silt loam with a higher organic carbon content. Samples of each aquatic sediment system were allowed to acclimatize before being treated with [14C]-acoramidis HCl at a nominal rate of 0.15 mg/L based on the amount of water in the test vessel including that present within the sediment. The samples were incubated under aerobic conditions at about 20 ±2°C in darkness for periods of up to 100 days.

Mean total recoveries of radioactivity (mass balances) for both aquatic sediments were between 94.8% and 100.6% applied radioactivity (AR).

In Calwich Abbey Lake aquatic sediment, the radioactivity in the water layer declined from a mean of 98.2% AR at time zero to 25.3% AR after 100 days of incubation. In sediment, the total extractable radioactivity increased to a mean of 44.2% AR after 59 days and remained at a similar level up to 100 days of incubation. The proportion of radioactivity remaining unextracted in the sediment increased to a mean of 23.3% AR after 100 days. Low levels of volatile radioactivity assumed to be associated with ¹⁴CO₂ was recovered in the trapping solutions, accounting for a maximum mean of 2.9% AR after 100 days.

Dissipation of radioactivity followed a similar pattern in the Lumsdale Middle Pond aquatic sediment. The radioactivity in the water layer declined from a mean of 94.4% AR at time zero to 26.9% AR after 100 days of incubation. In sediment, the total extractable radioactivity increased to a mean of 38.2% AR after 100 days of incubation. The proportion of radioactivity remaining unextracted in the sediment increased to a mean of 30.4% AR after 100 days of incubation. Little or no volatile radioactivity (maximum mean of 0.5% AR) was recovered in the trapping solutions up to 100 days.

Non-extractable radioactivity in the Calwich Abbey Lake sediment was mainly associated with the humin fraction and in the Lumsdale Middle Pond sediment was mainly associated with the fulvic acid and humin fractions.

DT₅₀ and DT₉₀ (at 20 ±2°C) values for the decline of acoramidis HCl from the water, the sediment and from the total aquatic sediment system are shown below.

Acoramidis HCl was degraded to 9 minor unique components and a polar material (up to a mean of 4.9% AR in the two-sediment total systems after 100 days), acoramidis HCl was incorporated into bound (non-extractable) radioactivity and mineralized to low levels of carbon dioxide.

This study reported a half-life of substance Acoramidis HCl in water DT₅₀ = 19.4-30.7 days and DT₅₀ = 146-341 in sediment/total system. Guideline OECD 308. (Reference VII)

Justification of chosen degradation phrase:

Acoramidis HCl established a DT₅₀ > 120 d for the total system and is resistant to hydrolysis, which qualifies for the phrase “Acoramidis HCl is potentially persistent.”

Bioaccumulation

Partitioning coefficient:

Log D_ow was reported to range from 2.39 to -0.69 for pH 5, 7 and 9 (additionally, while not relevant 2.51 at pH 4) and reported to be 0.52 at pH 7. Guideline OECD 107. (Reference VIII)

Justification of chosen bioaccumulation phrase:

As the log D_ow was < 4 acoramidis HCl is not considered bioaccumulative which qualifies for the phrase “Acoramidis HCl has low potential for bioaccumulation.”

References

1. 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

2. Acoramidis HCl: Algal Growth Inhibition Test. Bayer AG, Ecotoxicology. Report no. B003882, study no. 8473005.

3. Acoramidis HCl: Daphnia magna Reproduction Test. Bayer AG, Ecotoxicology. Report no. B003884, study no. 8473006.

4. Acoramidis HCl: Fish, Early Life Stage Toxicity Test. Bayer AG, Ecotoxicology. Report no. B003885, study no. 8473008.

5. Acoramidis HCl: Toxicity to Activated Sludge in a Respiration Inhibition Test. Bayer AG, Ecotoxicology. Report no. B003886, study no. 8473010.

6. Acoramidis HCl: Assessment of Ready Biodegradability; CO2 Evolution Test. Bayer AG, Ecotoxicology. Report no. B003881, study no. 8473019.

7. Acoramidis: Aerobic Transformation in Aquatic Sediment Systems. Bayer AG, Ecotoxicology. Report no. B004066, study no. 8494181.

8. AG10 HCI: Determination of log D. Bayer AG, Ecotoxicology. Report no. B003880, study no. MFG-660.