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 Human Exposure to Thimerosal from Vaccines Labeled for Use in Dogs  

Introduction
Thimerosal or Thiomersal is a mercury-containing compound used in canine and other animal vaccines as a preservative, inactivating agent, and/or adjuvant. Thimerosal is effective as a preservative as it inhibits the growth of microorganisms without alteration of vaccine potency. Preservative concentrations for veterinary vaccines are specified in Title 9, Code of Federal Regulations 114.10. However, the regulation only addresses antibiotics. Thimerosal use in veterinary vaccines appears to be largely unregulated. Because of this, human exposure to thimerosal from the administration of canine vaccines by veterinarians and others is unknown. Owners are potentially exposed when their dogs are vaccinated against DHPP (Distemper, Hepatitis Parvovirus, and Parainfluenza), Rabies, leptospirosis, lyme disease and canine influenza, especially when administering vaccines themselves. Depending on the vaccine type and formulation, vaccination can occur in dogs at either a one year or three year interval. Currently, rabies is the only vaccine required by law, and most states, if not all, only recognize rabies vaccinations administered by a licensed professional. thumb|Nobivac Canine DAPPv: One of a handful of Thimerosal-Free multi-dose, multivalent products

Uncertainties associated with a possible rise in the prevalence of neuro-developmental problems among children vaccinated with thimerosal-preserved vaccines prompted discontinued use in the U.S. since 2004 (with a few exceptions). Despite a lack of information of this risk, the United Nations Environment Programme is leading an effort to reduce and eliminate human exposure to mercury from all potential sources, including veterinary vaccines.

Toxicity of Thimerosal
Thimerosal is 49.6% mercury by weight. Thimerosal may present a risk when blood mercury concentration approaches or exceeds 1.0 μg ml-1 and severe intoxication occurs when blood mercury approaches or exceeds 2.0 μg ml-1.

Exposure Limits
No known occupational limits have been established for Thimerosal in the U.S. In several European countries, for skin the permissible exposure limit is 0.01 mg/m3 timed weight average and short-term exposure limit is 0.03 mg/m3.

Thimerosal in Canine Vaccines
There are approximately 180 monovalent and multivalent vaccines labeled for use in dogs. These products may be available in single dose or multi-dose formats. Unless a vaccine is labeled as Thimerosal-Free, it is assumed Thimerosal is used as a preservative, especially for multi-dose vaccines. A review of 30 randomly selected product labels for canine vaccines indicated that labeling on whether a product contained Thimerosal was inconsistent. In veterinary vaccines, Thimerosal was measured within the range of 47.4 ± 0.4 to 53.7 ± 0.7 µg per dose.

Estimating Accidental Exposure to Thimerosal
The following are considered in estimating chemical exposure:

Doses of Canine Vaccines Produced

 * In general, veterinary vaccine use information is very limited. In 2009, more than 305 million doses of canine vaccines were produced.  However, no data are available on how many of these doses are in combination products, Thimerosal-Free, packaged in single or multi-dose containers, and route of administration.

Extrapolation from Accidental Human Exposure to Other Veterinary Vaccines

 * Human exposure to Thimerosal from vaccines has been studied only from direct vaccination with human products. Thimerosal as a risk in veterinary settings has not been considered in published mercury exposure assessments. However, there are documented instances of exposure to Footvax®, an oil-based veterinary vaccine for sheep which also contains a small concentration of Thimerosal. In 3 patients, accidental self-inoculation resulted in extensive chronic granulomatous inflammation and sterile abscess formation.  While the mineral oil adjuvant was indicated as the cause of the adverse reactions, there is a possible association with Thimerosal (see Confounding Factors below).

Dermal

 * Mercury has a skin permeability coefficient in the order of 10–5 cm/h, which compares to permeability coefficients in the order of 10–4 cm/h for lead. As lead was considered to have negligible absorption, dermal absorption of mercury is considered to be a negligible route of exposure.

Inhalation

 * Mercury compounds are of concern in the vapor phase. Since injectable vaccines are not easily aerosolized, the exposure through inhalation will be negligible.

Ingestion

 * Estimates may be modeled using the conceptual model for inadvertent ingestion exposure in the workplace.

Needlestick injury (NSI)

 * NSI is the primary cause for concern because this represents the greatest exposure volume and entry is directly into the bloodstream and/or tissue. Through this route, mercury bypasses several physiological processing barriers, including the detoxifying entero-haptic system, and may migrate to the brain.

Populations exposed
There are 3 categories of concern: Veterinarians, Veterinary Technicians, and Other End-users. Available statistics for these categories are believed to be underreported. Standardization of reporting is required. Discussion below of prevalence rates is limited to NSI. However, similar analysis may be performed for ingestion.

Veterinarians

 * A study found the NSI of veterinarians in the U.S. at 74.2 per 100 person-years. This rate was similar to 75.3 per 100 person-years in Australian Veterinarians. However, this rate includes the entire spectrum of exposure in small, large, and mixed animal practices and includes all procedures involving needles. A separate study identified a higher rate in female veterinarians (may reflect a higher overall reporting rate) and 50% of the NSI involved vaccines.


 * Other studies have proposed using the estimated rate of 2 NSI per thousand inoculations in U.S. hospitals as a surrogate. However, this probably underestimates the NSI rate because vaccination conditions are different.

Veterinary Technicians

 * In a survey of 226 veterinary technicians, 74% experienced an NSI during the course of a year. From this percentage, 73% were working in a small animal practice, 8.4% were in a mixed animal practice, and 0.4% were in animal shelters.

Other End-users

 * While State and Local authorities do not recognize owner-administered vaccinations, it is estimated that 10-20% of pet dogs are vaccinated by non-veterinarians with products purchased through over-the-counter sources such as catalogs and web sites. There are no available statistics on NSI due to veterinary vaccine use by non-Veterinarians/Veterinary Technicians.

Magnitude
Magnitude will depend on the route of exposure. The average volume inoculated because of an NSI using an 18- to 22-gauge needle is up to 1 µL. Based on the upper limit of 54.4 µg Thimerosal per .5 ml dose (.01% Thimerosal concentration), 1 µL of vaccine contains .11 µg Thimerosal or .055 µg Mercury (based on weight). In a 70 kg male, this would equal a blood concentration of 1.1 X 10-5 μg ml-1.

Co-Exposure with Other Metals
There are concerns with combinations of thimerosal and other metals such as Aluminum in adjuvant formulations to create a more toxic effect. Additional studies are required.

Biosafety Practices
The use of a single layer of gloves was shown to reduce NSI exposure to contaminants by as much as 97%.