Animal testing methods for endocrine disruptors should change, team argues

June 25, 2014, University of Massachusetts Amherst

Challenging risk assessment methods used for decades by toxicologists, a new review of the literature led by environmental health scientist Laura Vandenberg at the University of Massachusetts Amherst suggests that oral gavage, the most widely accepted method of dosing lab animals to test chemical toxicity, does not accurately mimic how humans are exposed to chemicals in everyday life.

Oral gavage refers to the way researchers give chemicals to animals by putting a tube down their throats to deliver substances directly to the stomach. It has been used for decades and is at present the dosing scheme preferred for assessing potential toxicity of endocrine disrupting chemicals (EDC) by regulatory agencies.

Vandenberg, with colleagues at the University of Missouri-Columbia and Université de Toulouse, France, writes, "We conclude that gavage may be preferred over other routes for some environmental chemicals in some circumstances, but it does not appropriately model human dietary exposures for many chemicals. Because it avoids exposure pathways, is stressful and thus interferes with endocrine responses, gavage should be abandoned as the default route of administration for hazard assessments of EDCs."

Though gavage does offer precise dose and timing control, the authors say it is not appropriate for assessing EDCs, using Bisphenol A (BPA) as a primary example. Its drawbacks include the fact that gavage bypasses the mouth, which means animals experience "dramatic differences in absorption, bioavailability and metabolism" than humans experience when eating food, which is thought to be way most people are exposed to BPA. Further, gavage carries well-known risks including perforation of the esophagus that diminish its value.

Finally, the authors point out that the gavage protocol itself can induce stress responses in the endocrine system, which may confound EDC assessment. "We propose the exploration of alternatives to mimic human exposures when there are multiple exposure routes/sources and when exposures are chronic," they urge. Their work appears in the current issue of Environmental Health.

Vandenberg and colleagues say they chose BPA because exposure is widespread in humans, low doses have been linked to adverse effects in laboratory animals, exposure is linked to a wide range of human diseases, and unanswered questions remain about how best to model exposure routes and sources. The lack of detailed understanding of all potential routes of exposure applies to many chemicals used in a wide range of products, they add.

The researchers reviewed more than 60 papers and reports, pointing out that "for hypothesis testing, route of exposure may not be of central importance, but for hazard assessment, risk assessors typically require that studies use a route of exposure that is deemed 'relevant' to humans."

They point to recent studies in dogs and monkeys where scientists could study different BPA absorption when it was administered both by mouth and by traditional gavage. Given to dogs under the tongue, BPA entered into circulation largely in an unconjugated form, that is, without having been converted to an inactive form by the liver in so-called first-pass metabolism. By comparison, over 99 percent of the BPA was metabolized rapidly in the dogs with gavage. Similarly, less than 1 percent of administered BPA was bioavailable in blood in a gavage experiment with monkeys, while BPA fed in a piece of fruit resulted in over 7 percent of administered BPA being bioavailable in blood.

The authors point out that while "all dosing methods have pros and cons that must be considered in the design of a study," recent studies suggest that gavage may interfere with the study of EDCs and viable alternatives do exist. EDCs and drugs can be administered by milling a compound into feed, dissolving it in drinking water, feeding animals from a pipette or adding a compound to a wafer or other food. Also, implanted devices and osmotic pumps "are of particular interest in BPA studies because they can provide constant exposures to low doses that produce serum concentrations that approximate those found in humans. These routes of exposure may be relevant also because there are important and significant non-oral sources of BPA exposure," Vandenberg and colleagues state.

Explore further: Bisphenol A is affecting us at much lower doses than previously thought

Related Stories

Bisphenol A is affecting us at much lower doses than previously thought

November 7, 2013
Bisphenol A (BPA) is a known endocrine disruptor that hijacks the normal responses of hormones. Yet, traditional toxicology studies indicate that only very high doses of this chemical affect exposed animals—doses as high ...

BPA exposure during fetal development raises risk of precancerous prostate lesions

June 23, 2014
A new study has found for the first time that the endocrine-disrupting chemical bisphenol A (BPA) reprograms the developing prostate, making the gland more susceptible to precancerous lesions and other diseases later in a ...

Bisphenol A at very low levels can adversely affect developing organs in primates

February 27, 2014
Bisphenol A (BPA) is a chemical that is used in a wide variety of consumer products, such as resins used to line metal food and beverage containers, thermal paper store receipts, and dental composites. BPA exhibits hormone-like ...

Current chemical testing missing low-dosage effects of endocrine-disrupting chemicals

March 29, 2012
Endocrine-disrupting chemicals (EDCs) -- such as BPA -- can show tangible effects on health endpoints at high dosage levels, yet those effects do not predict how EDCs will affect the endocrine system at low doses, according ...

Common BPA-like chemical, BPS, disrupts heart rhythms in females

June 23, 2014
Bisphenol S (BPS), a common substitute for bisphenol A (BPA) in consumer products, may have similar toxic effects on the heart as previously reported for BPA, a new study finds. The results were presented Monday at the joint ...

BPA stimulates growth of breast cancer cells, diminishes effect of treatment

June 23, 2014
Bisphenol A (BPA), a chemical commonly used in plastics, appears to increase the proliferation of breast cancer cells, according to Duke Medicine researchers presenting at an annual meeting of endocrine scientists.

Recommended for you

Best of Last Year—The top Medical Xpress articles of 2017

December 20, 2017
It was a good year for medical research as a team at the German center for Neurodegenerative Diseases, Magdeburg, found that dancing can reverse the signs of aging in the brain. Any exercise helps, the team found, but dancing ...

Pickled in 'cognac', Chopin's heart gives up its secrets

November 26, 2017
The heart of Frederic Chopin, among the world's most cherished musical virtuosos, may finally have given up the cause of his untimely death.

Sugar industry withheld evidence of sucrose's health effects nearly 50 years ago

November 21, 2017
A U.S. sugar industry trade group appears to have pulled the plug on a study that was producing animal evidence linking sucrose to disease nearly 50 years ago, researchers argue in a paper publishing on November 21 in the ...

Female researchers pay more attention to sex and gender in medicine

November 7, 2017
When women participate in a medical research paper, that research is more likely to take into account the differences between the way men and women react to diseases and treatments, according to a new study by Stanford researchers.

Drug therapy from lethal bacteria could reduce kidney transplant rejection

August 3, 2017
An experimental treatment derived from a potentially deadly microorganism may provide lifesaving help for kidney transplant patients, according to an international study led by investigators at Cedars-Sinai.

Exploring the potential of human echolocation

June 25, 2017
People who are visually impaired will often use a cane to feel out their surroundings. With training and practice, people can learn to use the pitch, loudness and timbre of echoes from the cane or other sounds to navigate ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.