Environmental Safety Of Active Pharmaceutical Ingredients

Environmental Safety of Active Pharmaceutical Ingredients Dr. Richard Reiss Sciences International, Inc. October 20, 2005

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Introduction • Talk will focus on triclosan (TCS) and triclocarban (TCC) • For each chemical, I will provide: – – – –

General environmental fate characteristics Representative environmental concentration data Toxicity levels of most sensitive species Comparison of concentrations and toxicity levels

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General Environmental Fate Properties •

Both compounds have similar fate properties: – – –

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Both compounds will reach the environment through down-the-drain disposal –

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Both show significant degradation in water treatment plants (next slide)

TCS shows rapid removal from water column in dieaway studies (2-5 hour half-life) –

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Very low vapor pressures Soluble in water Highly adsorbent to organic matter

Also, biodegrades in soil in 17-35 days

TCC shows rapid degradation in biosolids (10 hour half-life) 3

Average Removal Rates in Wastewater Treatment Plants Actives

Activated Sludge

Trickling Filter

TCC

94%

77%

TCS

95%

83%

Predominant pathway is biodegradation

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Freshwater Aquatic Environmental Concentrations in U.S. for TCC Source TCC Consortium, 2002

Results •Max=0.23 ppb, 90% less than 0.05 ppb

Halden & Paull, •Max=6.8 2005

ppb in sites with significant raw

sewage

EPA E-FAST model, TCC consortium, 2002

•Model estimates, high-end at outfall = 0.017 ppb, median at outfall = 0.0013 ppb 5

Freshwater Aquatic Environmental Concentrations in U.S. for TCS Source

Study

USGS, 2002

•75th Percentile = 0.2 ppb, median of measured conc =0.14 ppb. Sampling locations chosen as “susceptible to contamination.”

USGS, 2004

• Non-detectable in typical flow conditions, Max=0.14 ppb in low flow conditions

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Most Sensitive Aquatic Species Actives

Chronic Toxicity and No Observed Effect Concentrations (NOECs)

TCC

Waterflea, Ceriodaphnia dubia, NOEC = 1.5 ppb Algae, 6 ppb, minimum algistatic concentration

TCS

Blue-green algae, NOEC = 0.5 ppb (algistatic, not algicidal, recovery in 3-6 days) Waterflea, Ceriodaphnia dubia, NOEC=6 ppb

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Comparison of Environmental Concentrations to NOECs for TCC

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TCC Consortium Measurements

1.4

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Comparison of Environmental Concentrations to NOECs for TCS

7 USGS Measurements

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Terrestrial Risk • Both TCS and TCC can be present in sewage sludge in small concentrations – Sludge may be used as soil amendments in agriculture – Low potential of exposure to ecological species

• Due to low mammalian toxicity, low sludge concentrations, and low potential for exposure, risks to ecological species are expected to be minimal (Federle et al., 2002) 10

Conclusions • The large majority of the TCC and TCS mass will degrade in treatment plants, but some will be present in effluent and sludge – Neither is expected to persist in the environment

• TCC shows low risk to aquatic species when high-end concentrations are compared to the no effect level for the most sensitive species

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Conclusions (cont) • TCS may have transitory algistatic effects on some algal species under worst case conditions and only in aquatic environments close to the effluent pipe – Downstream effects are not expected

• TCS is unlikely to have any significant effects on non-algal species

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