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) = 1.5*10^-6*A*(100-R)

PEC = 0.015 µg/L

Where:

A = 99.177 kg (total sold amount API in Sweden year 2019, data from IQVIA)

R = 0% removal rate (due to loss by adsorption to sludge particles, by volatilization, hydrolysis or biodegradation)

P = number of inhabitants in Sweden = 9*10⁶

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

D = factor of dilution of waste water by surface water flow = 10 (ECHA default) (Ref I)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Pseudokirchneriella subcapitata)
EC₅₀ 72 h (growth rate) = 35,6 mg/L = 35 600 μg/L
NOEC 72 h (growth rate) = 1,35 mg/L = 1350 μg/L

Guideline: OECD 201
(Ref II)

Crustacean (Daphnia magna)

Acute toxicity

EC₅₀ 48 h (immobilisation) = 84,3 mg/L = 84 300 μg/L

Guideline: OECD 202

(Ref III)

Fish (zebrafish embryos (Danio rerio)

Acute toxicity

LC₅₀ 96 h (mortality) > 100 mg/L = 100 000 μg/L
Guideline: OECD 236

(Ref IV)

Other ecotoxicity data

PNEC = 35.6 μg/L
e.g. PNEC (μg/L) = lowest EC₅₀/1000, where 1000 is the assessment factor used.

EC₅₀ for Pseudokirchneriella subcapitata has been used for this calculation since it is the most sensitive of the three tested species.

35 600 μg/L/1000 = 35.6 μg/L

Environmental Risk Classification (PEC/PNEC ratio)

PEC/PNEC = 0.015 µg/L/35.6 μg/L = 0.00042

PEC/PNEC ≤ 0.1 which justifies the phrase:

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

Degradation

Biotic degradation

Ready degradability

0 % in 28 days

Guideline: OECD 301F

(Ref V)

Justification of chosen degradation phrase:
Metoclopramid is potentially persistent.

Bioaccumulation

Partition coefficient

Log P = 2.667 (experimentally derived, method unknown, pH unknown)
(Ref VI)

Justification of chosen bioaccumulation phrase:

Since log P < 4 , metoclopramide has low potential for bioaccumulation.

Excretion (metabolism)

The excretion takes place in the urine. About 85 % of the dose is eliminated within 72 hours, 20-30 % as unchanged metoclopramide and the remainder as sulphate or glucuronide conjugate, or as other metabolites. About 5% is excreted in the faeces via the bile.
(Ref VII)

References

1. ECHA, European Chemicals Agency, 2008 Guidance on information requirements and chemical safety assessment. https://echa.europa.eu/guidance-documents/guidance-on-information-requirements-and-chemical-safety-assessment

2. Sanofi, Internal Report: Metoclopramide Hydrochloride Monohydrate: Toxicity to Pseudokirchneriella subcapitata in an Algal Growth Inhibition Test. Report # 117731210. 2017

3. Sanofi, Internal Report: Metoclopramide Hydrochloride Monohydrate: Acute Toxicity to Daphnia magna in a Static 48-hour Immobilisation Test. Report # 117731220. 2017

4. Sanofi, Internal Report: Metoclopramide Hydrochloride Monohydrate: Acute Toxicity to Zebrafish (Danio rerio) Embryos in a 96-hour Static Test. Report # 117731238. 2017

5. Sanofi, Internal Report: Metoclopramide hydrochloride: Ready Biodegradability in a Manometric Respirometry. Report # 117731163. 2017

6. Metoclopramide, retrived from DrugBank webpage 2021-04-22, find here

7. SmPC of Priperan, retrived from SE MPA webpage 2021-04-22, find here