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 = 0.017 µg/L

Where:

A = 127.4334 kg (total sold amount API in Sweden year 2020, 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 = 10*10⁶

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

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

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Algae (Anabaena flos-aquae):

EC₅₀ 72 h (growth rate): 90.9 µg/L

EC₁₀ 72 h (growth rate): 4.06 µg/L
NOEC 72 h (growth rate): 13.1 µg/L
Protocol: OECD 201
(Ref II)

Crustacean (Daphnia magna):

EC₅₀ 48 h (immobilization): > 109000 µg/L

NOEC 48 h (immobilization): > 109000 µg/L
Protocol: OECD 202
(Ref III)

Fish (Danio Rerio):

LC₅₀ 96 h (lethality): > 100000 µg/L
NOEC 96 h (lethality): > 100000 µg/L
Protocol: OECD 236
(Ref IV)

Other ecotoxicity data:

PNEC = Lowest EC₅₀/1000

Lowest EC₅₀:
Algae (Anabaena flos-aquae):
EC₅₀ 72 h (growth rate): 90.9 μg/L

PNEC: 90.9 μg/L/1000 = 0.091 μg/L

Environmental Risk Classification (PEC/PNEC ratio)
PEC/PNEC = 0.017/0.091 = 0.19

0.1 < PEC/PNEC ≤ 1 : Use of rifampicin has been considered to result in low
environmental risk.

Degradation

Biodegradation

Test showed 0 % degradation in 28 days.
OECD 301F. (Ref V)

Rifampicin is therefore potentially persistent.

Bioaccumulation

Rifampicin has high potential for bioaccumulation based on a calculated Log Kow = 4.24.

(Method: US EPA; Estimation Program Interface (EPI) Suite. Ver.3.11. June 10, 2003.)

(Ref VI)

Excretion

After absorption, rifampin is rapidly eliminated in the bile, and an enterohepatic circulation ensues. During this process, rifampin undergoes progressive deacetylation so that nearly all the drug in the bile is in this form in about 6 hours. This metabolite has antibacterial activity. Intestinal reabsorption is reduced by deacetylation, and elimination is facilitated. Up to 30 % of a dose is excreted in the urine, with about half as unchanged drug. (Ref VII)

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. Sanofi Internal report: Rifampicin: Toxicity to Anabaena flos-aquae in an Algal Growth Inhibition Test. OECD 201. Report 135371218 , November 2018.

3. Sanofi internal report: Rifampicin: Acute Toxicity to Daphnia magna in a Semi-Static 48-hour Immobilisation Test. OECD 202. Report 135371220, October 2018.

4. Sanofi internal report: Rifampicin: Acute Toxicity to Zebrafish (Danio rerio) Embryos in a 96-hour Semi-Static Test. OECD 236. Report 135371238, December 2018.

5. Sanofi internal report: Rifampicin: Ready Biodegradability in a Manometric Respirometry Test. OECD 301F. Report 135371163, October 2018.

6. US EPA; Estimation Program Interface (EPI) Suite. Ver.3.11. June 10, 2003. Available from, as of April 8, 2004: http://www.epa.gov/oppt/exposure/pubs/episuitedl.htm

7. Rifater® package insert, Sanofi-Aventis U.S., April 2013.