# Presentation: 528808

## Veterinary Pharmaceuticals: Potential Environmental Impact and Treatment Strategies

-      **John L. Cicmanec, DVM, MS, ACLAM**
**   ****US EPA, Cincinnati, OH**

## Groups of Compounds

- Antibiotics
- Anthelmintics
- Hormones; steroids and bovine     somatotropin
- Pesticides
- Vaccines
- X-Ray contrast media, iodine & barium based

## US Pesticide Use

- 4.5 billion pounds chemicals per year
- 890 active ingredients, 30,000 formulations
- Uses
- 75% agricultural
- 25% home, garden, structural

## Unintentional Pesticide Illness, USA        Toxic Exposure Surveillance System 1993-1996

**Notes:**
The Toxic Exposure Surveillance System (TESS) are data compiled from the majority of US poison centers and are used to identify hazards to focus research and prevention.  The log scale graph depicts pesticide classes and severity of illness reported by TESS.  For the years 1993 to 1996, pesticides were among the top 10 substances involved in human exposures.  For this time period, there were 87,000 symptomatic pesticide exposures, mostly due to insecticides.  Disinfectants were the next most common type of pesticide exposure.
While most pesticide illnesses were categorized as being of minor severity, pesticide exposures did cause more severe illnesses and a few fatalities, mostly among children.
This data represents an undercount of actual pesticide illness, since all states were not included in TESS, and since not all illnesses are reported to poison control centers.

## Multi-ingredient Products

**Swisher Super Broiler 300-108**
-        Bacitracin, ethopabate, amprolium
**Aureomix S-700**
-       chlortetracycline, sulfamethazine
**Banmith**
-        carbadox, pyrantel

## Potential Endocrine Disrupting Chemicals

- Trenbolone acetate (RevalorR, FiniplexR)
- Melengestrol acetate
- Estradiol benzoate
- Testosterone proprionate
- Human chorionic gonadotropin
- Prostaglandins

## Trenbolone & Melengestrol

**Little is known about their fate after excretion by the animal**
**Trenbolone half-life when stored as liquid manure is **_**267 days**_
**In farm field studies ****Trenbolone**** was detected at the end of fertilizer application and ****Melengestrol****  was detected at harvest**

## Categories of Antibiotics 

**Sulfonamides –    sulfamethoxazole, etc**
**Quinolones-         Ciprofloxacin**
**Beta-lactams-       penicillins,             **
**                               ****cephalosporins**
**Aminoglycosides- streptomycin, **
**                                ****gentamycin**
**Macrolides –         erythromycin, tylosin**

## Antibiotic Use by Compound Class (1999)

-  _Antibiotic_ _Class_                 _Percentage_
-   Aminoglycosides                             1
-   Fluoroquinolones                             0.1_ _
-   Ionophores/Arsenicals                  47
-   Penicillins                                        4
-   Sulfonamides                                  2
-   Tetracyclines                                16
-   Other Classes                               29

## Testing for Antibiotic Resistance in the Laboratory

**Testing for Antibiotic Resistance in the Laboratory**

## Species Comparisons of Resistance in E. coli

**Notes:**
Animal isolates exhibit a much higher prevalence of tetracycline resistance than human isolates
The patterns observed among the resident geese (who have access to lagoons and feed) are very similar to those observed among the swine isolates
Human isolates exhibit a higher prevalence of trimethoprim and florfenicol resistance than animal isolates

## Species Comparisons of Resistance in Salmonella 

## A Snapshot of Antibiotic Use

-          _***Europe***_
**10,900 tons combined Use (1998)**
- 7000 tons-human use
- 3900 tons-animal use

-     _***United***_*** ***_***States***_
**12,000 tons combined Use (1997)**
- 4800 tons-human use
- 7200 tons-animal use

## Animal Antibiotics in the Environment

- Presently in Europe only 4 antibiotics - monensin, avilamycin, flavomycin, & salinomycin are approved for animal use
- Primarily the macrolides & sulfonamides persist in the environment
- Tetracyclines, penicillins & fluoroquinolones rapidly degrade
- Concentrations found-usual 1-5 ng/L but can range up to 300 ng/L

## Full-scale Anaerobic Digester near 

- Full-scale Anaerobic _Digester_ near
- Nevada, IA, Crawford Swine Farm

## Results of Screening StudyTylosin Tartrate -10 mg/L (α=0.05)

## Generic Conceptual Models

- Resistant
- Pathogen

- Contamination of Food Supply

- AR Disease: Food-borne Illness

- Resistant
- Commensal

- Contamination of Food Supply

- AR Disease: Opportunistic AR Infection

- Human AR Carriers

*Human Populations*

*Food Animals*

- Relapsed
- AR Disease

- Food-borne Illness

**Pathogenic Bacteria**

**Commensal Bacteria**

## European and U. S. Data

**Resistance in Retail Meat**
**Poultry: 30 - 60% have Streptogramicin-resistant Enterococcus faecalis (SREF)**
**Also present in Pork and Beef products**
**Incidence among Humans**
**US: 0.4 - 1% have SREF**
**Europe: up to ~10% reported**

## Linking Animal & Human Use

- Animal Drug - Virginiamycin
**Streptogramin (Group B)**
**Used in animals for > 26 years**
**Used as growth promoter at sub-therapeutic levels**
- Human Drug - Synercid
**Streptogramin - Quinupristin/Dalfopristin combination**
**Approved for therapy in US (1999) **
**Active against Gram-positive bacteria  -**** ****“drug of last resort”**

## Principal Drugs Used in Fish Hatcheries

- Benzalkonium chloride
- Copper sulfate
- Chloramine-T
- Malachite green
- Methyl testosterone
- Oxytetracycline
- Luteinizing Hormone Releasing Hormone

## Arsenicals

**Commonly used in Poultry feed as growth promoters**
**Consumption of 60 gm/day of chicken exposes the consumer to 1-5μg/day of inorganic As**
**Consumption of 350 gm/day of chicken (the 95%) – 32-47μg/day**
**   ****(The RfD is 2.1 μg/day)**

## Processes to Remove Pharmaceuticals

**Sorption to particles**
**Ultraviolet light**
**Bacterial degradation**
**Reverse osmosis**
**Bank filtration**
**Natural attenuation**
**Nanofiltration**
**Photolysis**

## What we can Learn from Studies of Human Pharmaceuticals

- Most persistent drugs are diazepam, carbamazepine, bezafibrate,& iopromide
- Elimination from wastewater depends primarily upon _sludge retention time_
- For activated sludge systems _4-5 days_ are needed; for nitrogen removal _8-20 days_

## Human Pharmacokinetic Data (from Goodman & Gilman “The Pharmacologic Basisof Therapeutics, 7th Edition, 1999)

- _Drug_                _Percent_ _Bound_       H_alf-life_ (hr)
- Carbamazepine          74                     15
- Diazepam                   98                     43
- Trimethaprim              44                     11
- Clofibrate                    96                     13
- Acetominophen            0                       2
- Streptomycin              48                       2.6

## Summary

**Presently antibiotic-resistance and Endocrine Disrupting Chemicals have been shown to have the greatest potential for causing environmental damage**
**The vast quantities of compounds  and wide-spread distribution make Veterinary Pharmaceuticals a significant environmental challenge**
**Product control and distribution is more complex than for Human Pharmaceuticals**