NAS: EPA should limit pesticide studies on humans (fwd)

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Date: Sun, 22 Feb 2004 07:50:16 +0000 (UTC)

From: Angel Para <jap2bep@...>

Angel MCS <jap2bemc@...>, ntefusa@...

Subject: [OEM] NAS: EPA should limit pesticide studies on humans (fwd)

The Laws of Ecology: " All things are interconnected. Everything goes

somewhere. There's no such thing as a free lunch. Nature bats last. "

Ernest Callenbach

" If having endured much, we at last asserted our 'right to know' and if,

knowing, we have concluded that we are being asked to take senseless and

frightening risks, then we should no longer accept the counsel of those

who tell us that we must fill our world with poisonous chemicals, we

should look around and see what other course is open to us. "

Carson

" My toxicasa (world) is your toxicasa (world). "

Judith Goode

http://www4.nationalacademies.org/news.nsf/isbn/0309091721?OpenDocument

Date: Feb. 19, 2004

Contacts: Vanee Vines, Media Relations Officer

Mc, Media Relations Assistant

Office of News and Public Information

202-334-2138; e-mail <news@...>

Full Report:

http://books.nap.edu/catalog/10927.html?onpi_newsdoc021904

FOR IMMEDIATE RELEASE

EPA Should Impose Stringent Scientific and Ethical Standards on Studies

That Deliberately Expose People to Toxins, and Evaluate Such Experiments

To Ensure That Standards Have Been Met

WASHINGTON – When regulating chemicals to protect public health, the

U.S. Environmental Protection Agency should consider information from

studies that involve intentional dosing of humans with toxic chemicals

only if such experiments meet the most stringent scientific and ethical

standards, ensuring that research participants are protected and that

the studies are scientifically necessary and valid, says a new report

from the National Academies' National Research Council. At the same

time, EPA should establish a Human Studies Review Board (HSRB) to

evaluate all human dosing studies – both at the beginning and upon

completion of the experiments – if they are carried out with the intent

of affecting the agency's policy-making. Human testing of chemicals must

be approached with the utmost caution and care, warned the committee

that wrote the report.

" Human studies involving pesticides, air pollutants, or other toxicants

– as opposed to therapeutic agents – are particularly controversial, and

because of this, EPA should subject these studies to the highest level

of scientific and ethical scrutiny, " said committee co-chair F.

Childress, a professor of ethics and medical education, and director,

Institute for Practical Ethics, University of Virginia, Charlottesville.

" Our report proposes a framework for EPA's oversight of this research.

And the recommended framework should apply to studies that are sponsored

by so-called 'third parties' – private companies or other sources

outside the agency – as well as by EPA. "

The issue of whether – and if so, how – EPA should use information from

such studies when formulating regulations has long been highly

controversial. In 1996 Congress passed the Food Quality and Protection

Act, which tightened safety standards on pesticides. Some chemical

manufacturers asserted that the new standards and " reference doses " were

not based on a solid scientific foundation. In support of this

assertion, several companies sponsored or conducted clinical trials to

assess human risk from exposure to pesticides and submitted the results

to the agency for consideration. Some public health advocates and

others, questioning the industry's research findings, urged the agency

to reject the results.

In response to the controversy, EPA announced in 1998 that it would not

use the studies to inform its policy-making until many ethical and

scientific issues had been resolved. Later, a majority of a joint

subcommittee of EPA's Science Advisory Board and the Federal

Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel

concluded that human dosing studies could be ethically and

scientifically justified under certain circumstances, subject to

stringent conditions and oversight. EPA sought a broader scientific

review from the National Academies evaluating key issues of third-party

human dosing studies of pesticides and of some chemical regulatory

programs within the agency. EPA itself has sponsored human dosing

studies of air pollutants and other potentially hazardous chemicals when

it considered the studies necessary to set health-related regulations.

But typically, EPA assesses human risk from exposure to toxic substances

by determining the lowest level that is harmful to laboratory animals

and then reducing that amount by a series of extrapolating factors.

Setting a High Bar

As part of its comprehensive review of the science base, the Research

Council committee evaluated intentional human dosing studies that were

voluntarily submitted by a number of pesticide companies which had

previously submitted their results to EPA. It also reviewed information

about human dosing studies that had been sent to the agency's Office of

Pesticide Programs. And it held a public forum last year to receive

input from various groups and individuals.

The committee recommended that intentional dosing studies in humans be

conducted and used for EPA regulatory purposes only if all of the

following conditions are met:

¨ Studies must be necessary and scientifically valid, addressing

important regulatory questions that cannot be answered with animal

studies or other studies that do not involve human testing. They must be

designed, conducted, and reported in a scientifically rigorous manner to

ensure that they answer a specific research question.

¨ The possible benefits to society from such studies must outweigh any

anticipated risks to participants.

¨ Studies whose results would be used for the sole purpose of improving

the scientific accuracy of EPA's established reference doses for humans,

and that would not provide health benefits otherwise, would be justified

only if there were no identifiable risks to participants, or if

investigators could show with reasonable certainty that participants

would not be harmed.

¨ All of the recognized ethical standards and procedures for protecting

the interests of study participants must be observed, including

equitable selection and recruitment of human subjects, the obtaining of

informed consent, and independent review of the scientific and ethical

merits of a given study by an institutional review board (IRB) or its

equivalent.

Extra safety measures mandated by the 1996 Food Quality and Protection

Act (FQPA) to protect children would not be affected by the use of data

from intentional dosing studies in humans, the report adds; dosing

studies in children generally would be unethical. Also, information

directly relevant to children cannot be obtained from these types of

dosing studies in adults.

The committee concluded that EPA should use data from third-party human

dosing experiments to establish reference doses for organophosphates and

carbamates only if the agency thoroughly reviews the studies and finds

that they meet the conditions listed above – the same process EPA should

employ when weighing all studies that involve intentional human dosing

with toxins. These classes of pesticides were among the most hotly

disputed during the debate over the FQPA. They can interfere with proper

functioning of the nervous systems of not only insects, but also humans

and other vertebrates.

On the whole, oversight in this area is crucial, the committee said. A

careful risk assessment is a prerequisite from the outset. EPA should

require that all human research conducted for regulatory purposes be

approved in advance by IRBs or by acceptable equivalents in other

countries. To supplement IRB oversight, the proposed Human Studies

Review Board also should evaluate in advance all intentional human

dosing studies being proposed for use in formulating regulations, to

ensure that the studies meet high scientific and ethical standards –

whether the research is sponsored or carried out by the agency. Private

entities should be strongly encouraged to voluntarily submit their

research plans to the HSRB before beginning a study. This board's

conclusions would be advisory only. Its functions and track record

should be assessed after five years by a group of EPA staff and external

reviewers.

" The committee purposely set a very high bar when it comes to

intentional human dosing studies, especially for those that do not

promise health or environmental benefits, " said committee co-chair

R. , senior fellow and director of the risk, resource, and

environmental management division, Resources for the Future, Washington,

D.C. " Improving the quality of the science used for regulatory purposes

is itself a worthy social goal, but it could never justify harming human

research participants. "

Protecting Research Participants

The relevant benefits that might be associated with any ethically sound

and scientifically valid and necessary dosing studies would be societal.

For example, a human study of an air pollutant could provide essential

data to establish or strengthen environmental standards, aiding the

public at large. Studies that could possibly cause adverse effects must

have a very high likelihood of producing significant health or

environmental benefits if they are to be undertaken. But even those

studies could not be ethically justified if they might cause long-term

harm to participants.

Research participants should be representative of the target population,

and scientific investigators should take steps to avoid exploitation of

any particular social group, the report says. All parties involved in

designing and evaluating a research protocol should consider whether the

proposed level of remuneration given to participants would constitute

exploitation or offer an undue incentive to take part.

Voluntary, informed consent by research participants is another

principal requirement, the report says. In this area, EPA should develop

and disseminate to relevant IRBs, investigators, and research sponsors a

list of " best practices " regarding informed consent in intentional human

dosing studies. It also should encourage stakeholders to implement the

measures and require their adoption in studies that the agency itself

sponsors or carries out. Sponsors of or institutions conducting human

dosing studies also should ensure that participants receive necessary

medical care, free of charge, for any injuries they might incur from

their involvement in research.

The study was sponsored by the U.S. Environmental Protection Agency. The

National Research Council is the principal operating agency of the

National Academy of Sciences and the National Academy of Engineering. It

is a private, nonprofit institution that provides science advice under a

congressional charter. A committee roster follows.

Copies of Intentional Human Dosing Studies for EPA Regulatory Purposes:

Scientific and Ethical Issues are available from the National Academies

Press; tel. 202-334-3313 or 1-800-624-6242 or on the Internet at

http://www.nap.edu. Reporters may obtain a copy from the Office of News

and Public Information (contacts listed above).

NATIONAL RESEARCH COUNCIL

Division on Policy and Global Affairs

Science, Technology, and Law Program

Committee on the Use of Third-Party Toxicity Research with Human

Research Participants