Environmental Safety of Active

Pharmaceutical Ingredients

Dr. Richard Reiss

Sciences International, Inc.

October 20, 2005

1
 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

2
 General Environmental
Fate Properties
• Both compounds have similar fate properties:
– Very low vapor pressures
– Soluble in water
– Highly adsorbent to organic matter
• Both compounds will reach the environment
through down-the-drain disposal
– Both show significant degradation in water treatment plants
(next slide)
• TCS shows rapid removal from water column in die-
away studies (2-5 hour half-life)
– 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 Trickling Filter
Sludge

TCC 94% 77%

TCS 95% 83%

Predominant pathway is biodegradation 4

 Freshwater Aquatic Environmental
Concentrations in U.S. for TCC
Source Results

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

Consortium,
2002

Halden & Paull, •Max=6.8 ppb in sites with significant raw

2005
sewage

EPA E-FAST •Model estimates, high-end at outfall =

model, TCC
consortium, 0.017 ppb, median at outfall = 0.0013 ppb
2002
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

6
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

7
 Comparison of Environmental
Concentrations to NOECs for TCC

1.6
TCC Consortium
Measurements
1

1.4 8
 Comparison of Environmental
Concentrations to NOECs for TCS

7
USGS Measurements

9
 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

11
 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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