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 = 0.0842 μg/L

Where:

A =561.265 kg (total sold amount API in Sweden year 2019, data from IQVIA).

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)(Reference 1)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Reference 1)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae (Selenastrum capricornutum):

IC50 72h (inhibition of growth rate) = 70 μg/L (OECD 201) (Reference 3)

Water flea (Daphnia magna):

Acute toxicity

EC50 48 h (immobility) = 70 μg/L (OECD 202) (Reference 3)

Orange red Killfish (Juvenile Poecilia reticulata):

Acute toxicity

LC50 96 h (immobility) = 240 μg/L (OECD 203) (Reference 3)

Other ecotoxicity data:

Microorganisms in activated sludge

EC50 3 hours (Inhibition) = 35,000 μg/L (OECD 209) (Reference 3)

PNEC = 70/1000 = 0.07 μg/L

PNEC (μg/L) = NOEC/1000, where 1000 is the assessment factor recommended for three acute toxicity studies (Reference 1). The EC50 for green algae (= 70 µg/L) has been used for this calculation.

Environmental risk classification (PEC/PNEC ratio)

PEC/PNEC = 0.0842/0.07 = 1.20, i.e. 1 < PEC/PNEC ≤ 10 which justifies the phrase “Use of benzoyl peroxide has been considered to result in moderate environmental risk”.

Degradation

Biotic degradation

Ready degradability:

83%, 20 day MITI Test, OECD 301C (Reference 3)

Inherent degradability:

No data

Abiotic degradation

Hydrolysis:

No data

Photolysis:

No data

Justification of chosen degradation phrase:

Benzoyl peroxide is readily biodegradable the phrase “Benzoyl peroxide is degraded in the environment" is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log Kow = 3.43 (Reference 3)

Justification of chosen bioaccumulation phrase:

Since log Kow < 4, the substance has low potential for bioaccumulation.

Excretion (metabolism)

The presence of benzoyl peroxide in the formulation did not have an effect on the percutaneous absorption of clindamycin. Radio-label studies have shown that absorption of benzoyl peroxide through the skin can only occur following its conversion to benzoic acid. Benzoic acid is mostly conjugated to form hippuric acid, which is excreted via the kidneys. (Reference 2)

PBT/vPvB assessment

Benzoyl peroxide 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). Benzoyl peroxide does not fulfil the criteria for PBT and/or vBvP based on a log Kow < 4 and is readily biodegradable.

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. Pharmacokinetic properties: Metabolism and Elimination. Summary of Product Characteristics DUAC once Daily 10mg/g and 30mg/g Gel. Stiefel, March 2018.

3. DUAC Topical Gel. MSDS ID 133364, version # 6. GlaxoSmithKline, September 2018

4. Instant J Chem Log P and LogD. Sep 2012. Chemaxon Inc.

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 = 0.144 μg/L

Where:

A = 1,049.85 kg (total sold amount API in Sweden year 2020, data from IQVIA). Total volume of Clindamycin phosphate = 79.07 = 66.42 clindamycin free base. Total volume of Clindamycin hydrochloride 983.43 = 904.66 clindamycin free base. Total volume of Clindamycin palmitate hydrochoride = 17.63 = 10.83 clindamycin free base. Total Clindamycin = 66.42 + 983.43 + 10.83 = 1,049.85.

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 = 10 *10⁶

V (L/day) = volume of wastewater per capita and day = 200 (ECHA default) (Reference 1)

D = factor for dilution of waste water by surface water flow = 10 (ECHA default) (Reference 1)

Predicted No Effect Concentration (PNEC)

Ecotoxicological studies

Green Algae (Pseudokirchneriella subcapitata):

EC50 (inhibition of growth rate) = 4.1 μg/L (OECD 201) (Reference 3)

EC10 = 0.98 μg/L

Water flea (Daphnia magna):

Acute toxicity

No data

NOEC = 1,000,000 μg/L

Chronic toxicity

No data

Fish:

Acute toxicity

No data

Chronic toxicity

No data

Other ecotoxicity data:

Microorganisms in activated sludge:

No data

PNEC cannot be calculated because data is not available for all three (algae, crustacean and fish) of the toxicity endpoints.

Environmental risk classification (PEC/PNEC ratio)

Risk of environmental impact of clindamycin cannot be excluded, since there is not sufficient ecotoxicity data available.

Degradation

Biotic degradation

Ready degradability:

No data

Inherent degradability:

No data

Abiotic degradation

Hydrolysis:

No data

Photolysis:

No data

Justification of chosen degradation phrase:

The phrase “The potential for persistence of Clindamycin is cannot be excluded, due to lack of data” is thus chosen.

Bioaccumulation

Partitioning coefficient:

Log Dow_calc at pH 5 = -1.47 (QSAR) (Reference 4)

Log Dow_calc at pH 7 = 0.38

Log Dow_calc at pH 9 = 1.02

Justification of chosen bioaccumulation phrase:

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

Excretion (metabolism)

In an open-label study of 24 patients with moderate-to-severe acne vulgaris, approximately 4 grams of Duac Once Daily 10 mg/g + 30 mg/g Gel was applied once daily for 5 days to the face, upper chest, upper back, and shoulders. Geometric mean maximal plasma clindamycin exposure (Cmax) on Day 5 was 0.961 ng/mL with an AUC∞ of 12.9 ng*hr/mL.

In a maximised percutaneous absorption study the mean plasma clindamycin levels during a four-week dosing period for clindamycin 10 mg/g + benzoyl peroxide 50 mg/g gel were negligible (0.043 % of applied dose). (Reference 2).

PBT/vPvB assessment

Clindamycin does not fulfil the criteria for PBT and/or vPvB

All three properties, i.e. ‘P’, ‘B’ and ‘T’ are required in order to classify a compound as PBT (Reference 1). Clindamycin 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. Pharmacokinetic properties: Metabolism and Elimination. Summary of Product Characteristics DUAC once Daily 10mg/g and 30mg/g Gel. Stiefel, March 2018.

3. https://www.amrindustryalliance.org/wp-content/uploads/2018/09/AMR_Industry_Alliance_List-of-Predicted-No-Effect-Concentrations-PNECs.pdf

4. Instant J Chem Log P and LogD. Sep 2012. Chemaxon Inc.