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 = 6.14 x 10^-4 μg/L

Where:

A = 4.09 kg (total sold amount API in Sweden year 2020, data from IQVIA). Reduction of A may be justified based on metabolism data.

R = 0% removal rate (conservatively, it has been assumed there is no 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 for dilution of waste water by surface water flow = 10 (ECHA default) (Ref. I)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae (Scenedesmus subspicatus):

IC50 72 h (growth) > 4,200 μg/L (OECD 201) (Reference 4)

NOEC = 1,400 μg/L

Water flea (Daphnia magna):

Acute toxicity

EC50 48 h (immobility) > 1,400 μg/L (OECD 202) (Reference 3)

NOEC = 400 μg/L

Water flea:

Chronic toxicity

No data

Rainbow Trout (Oncorhyncus mykiss):

Acute toxicity

LC50 96 h (lethality) > 750 μg/L (OECD 203) (Reference 5)

NOEL = 750 μg/L

Chronic toxicity

No data

Other ecotoxicity data:

Microorganisms in activated sludge:

EC50 3 h (inhibition) > 100,000 μg/L @ 3 hrs (OECD 209) (Reference 6)

NOEC = 100 000 μg/L

PNEC = 750/1000 = 0.75 μg/L

PNEC (μg/L) = PNEC (μg/L) = lowest EC50/1000, where 1000 is the assessment factor applied for three short-term EC50s. As EC50 are greater than values the lowest potential EC50 for fish (= 750 µg/L) has been used for this calculation since it is the most sensitive of the three tested species.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 6.14 x 10^-4/0.75= 8.19 x 10^-4, i.e. PEC/PNEC ≤ 0.1 which justifies the phrase “Use of Clobetasol propionate has been considered to result in insignificant environmental risk.”

Degradation

Biotic degradation

Ready degradability:

No data

Inherent degradability:

< 5% primary(removal of parent) degradation in 14 days (OECD 302). (Reference 7)

Abiotic degradation

Hydrolysis:

No data

Photolysis:

No data

Justification of chosen degradation phrase:

Clobetasol propionate is not readily degradable or inherently biodegradable. The phrase “Clobetasol propionate is potentially persistent” is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log Pow = 3.49 (TAD 3.02) (Reference 8)

Log Pow_calc = 3.1 (Reference 9)

Justification of chosen bioaccumulation phrase:

Since log Dow < 4 at pH 7, the substance has low potential for bioaccumulation.

Excretion (metabolism)

There are no human data regarding the distribution of corticosteroids to body organs following topical application. Nevertheless, once absorbed through the skin, topical corticosteroids are handled through metabolic pathways similar to systematically administered corticosteroids. They are metabolized primarily in the liver, and are then excreted by the kidneys. In addition, some corticosteroids and their metabolites are also excreted in the bile (Reference 2).

PBT/vPvB assessment

Clobetasol propionate does not fulfil the criteria for PBT and/or vBvP.

All three properties, i.e. ‘P’, ‘B’ and ‘T’ are required in order to classify a compound as PBT (Reference 1). Clobetasol does not fulfil the criteria for PBT and/or vBvP based on log Dow < 4.

Please, also see Safety data sheets on http://www.msds-gsk.com/ExtMSDSlist.asp

References:

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

2. Clobex (clobetasol propionate) FDA label issued on 2005-11-01

3. Magor SE and Kent SJ. Clobetasol 17-Propionate: Acute Toxicity to Daphnia magna. Report No. BL7712/B. Brixham Environmental Laboratory Limited, June 2004.

4. Magor SE, Kent SJ and Young BE. Clobetasol 17-Propionate: Toxicity to Green Alga Selenastrun capricornutum. Report No. BL7713/B. Brixham Environmental Laboratory Limited, August 2004.

5. Magor SE and Kent SJ. Clobetasol 17-Propionate: Acute Toxicity to Rainbow Trout (Oncoryhynchus mykiss). Report No. BL7714/B. Brixham Environmental Laboratory Limited, June 2004.

6. Swarbrick RH and Smyth DV. Clobetasol 17-Propionate: Effect on the Respiration Rate of Activated Sludge. Report No. BL7715/B. Brixham Environmental Laboratory Limited, May 2004.

7. Magor SE, Kent SJ and Young BE. Clobetasol 17-Propionate: Determination of Inherent Biodegradability (Zahn-Wellens Test). Report No. BL7712/B. Brixham Environmental Laboratory Limited, August 2004.

8. MSDS ID 25278. Clobetasol propionate. GlaxoSmithKline plc, February 2011.

9. ACD /LogD. May 2012. Advanced Chemistry Development, Inc.