Dr. Richard Reiss

1
Environmental Safety of Active Pharmaceutical
Ingredients

• Dr. Richard Reiss
• Sciences International, Inc.
• October 20, 2005

2
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

3
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)

4
Average Removal Rates in Wastewater Treatment
Plants
Actives Activated Sludge Trickling Filter
TCC 94 77
TCS 95 83
Predominant pathway is biodegradation
5
Freshwater Aquatic Environmental Concentrations
in U.S. for TCC
Source Results
TCC Consortium, 2002 Max0.23 ppb, 90 less than 0.05 ppb
Halden Paull, 2005 Max6.8 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
6
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, Max0.14 ppb in low flow conditions
7
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, NOEC6 ppb
8
Comparison of Environmental Concentrations to
NOECs for TCC
TCC Consortium Measurements
9
Comparison of Environmental Concentrations to
NOECs for TCS
USGS Measurements
10
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)

11
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

12
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