Daminozide - WikiHQ

Daminozide, also known as aminozide, Alar, Kylar, SADH, B-995, B-nine, is an organic compound which acts as a plant growth regulator. When consumed by mammals, daminozide is catabolised into succinic acid (a non-toxic general intermediate in primary metabolism) and 1,1-dimethylhydrazine (UDMH, a compound with a history of studies associating it with carcinogenic activity in animal models relevant to humans). Breakdown into these two compounds also occurs when the sprayed chemical residue remains on stored fruit, especially with higher temperatures and over longer time periods.

In 1989, the EPA outlawed daminozide on U.S. food crops, but still allowed it for non-food crops like ornamental plants. As of August 2022, daminozide appeared as severely restricted in its exports on the list of pesticides whose shipments were ineligible for export credit insurance under the Export–Import Bank of the United States. it is actually a product of the condensation of succinic anhydride with unsymmetrical dimethylhydrazine (UDMH), and therefore better classified as either a dicarboxylic acid or hydrazine:

In its pure form, it is an off-white, water-soluble crystalline solid.

Modes of action

Daminozide is classified as a plant growth regulator, a chemical sprayed on fruit to regulate their growth. They submitted the proposal to the Scientific Advisory Panel (SAP), which concluded that the tests were inadequate to determine the carcinogenicity of the tested substances.

Later, in May 1989, Democrats Joseph Lieberman (D-CT) and Harry Reid (D-NV) held a press conference in which the pesticide program at the FDA was accused of being "riddled with pro-industry bias", charging that 7 of 8 SAP members had worked as "consultants for the 'chemical industry'" — that the worst of them, after serving on the SAP (see below), had "later broke[n] conflict-of-interest laws", with career university academic toxicologists Wendell Kilgore and Christopher Wilkinson (29 years, UCal-Davis and 22 years, Cornell) being singled out as "possible violators of the [FDA] ethics code", with invitation to the "EP[A] inspector general [IG] to investigate". Marshall Elliot, writing for the News & Views section of the AAAS publication, Science, noted that these Senators' public scolding of SAP members—which was prompted by the FDA's "waffling on Alar"—led to the investigation of just these two academics by that agency's IG, and of forwarding of Kilgore's file to the U.S. Justice Department for review. notably, the key formal contention was of possible violation of FDA ethics rules regarding limits to the "kind of consulting jobs that can be accepted after leaving an advisory panel" [emphasis in original source]. Oakes presented the report's argument that children ingesting daminozide in legally permissible quantities were at "intolerable risk" (from it and a wide variety of other potentially harmful chemicals); by their estimate, Oakes said, the "average pre-schooler's exposure to this carcinogen... result[s] in a cancer risk '240 times greater than the cancer risk considered acceptable by E.P.A. following a full lifetime of exposure.'" In February, 1989, the CBS television program 60 Minutes broadcast a story about Alar that featured the NRDC report highlighting problems with the chemical.

Later in 1989, the U.S. Environmental Protection Agency (EPA) decided to ban Alar on the grounds that "long-term exposure" posed "unacceptable risks to public health." However, in June 1989—before the EPA's preliminary decision to ban all food uses of Alar went into effect—Uniroyal, Alar's sole manufacturer, agreed to halt voluntarily all domestic sales of Alar for food uses. Hence, the consequences of CBS broadcast were swift and severe; as Percival, Schroeder, Miller, and Leape note in review of legal aspects in their Environmental Regulation text,<blockquote>"The denouement... came quickly. Alar was removed from the apple market by its manufacturer, not because of regulatory requirements imposed by the EPA, but because of consumer pressure"</blockquote>In particular, the "rapid decline in apple consumption that followed the "60 Minutes" report"

Backlash

In November 1990, Washington apple growers filed a lawsuit in Yakima County Superior Court against CBS, NRDC and Fenton Communications (hired by NRDC to publicize their report on Alar) claiming that unfair business practices (product disparagement in particular) cost them $100 million. The suit was moved from state to federal court at the request of CBS. U.S. District Judge William Fremming Nielsen ruled in 1993 that the apple growers had not proved their case, and it was subsequently dismissed by the United States Court of Appeals for the Ninth Circuit.

Elizabeth Whelan and her organization, the American Council on Science and Health (ACSH), which had received $25,000 from Alar's manufacturer, stated that Alar and its breakdown product UDMH had not been shown to be carcinogenic. During a 1990 speech at Hillsdale College, Whelan said that groups like the NRDC were ignoring a basic principle of toxicology: the dose makes the poison. "It is an egregious departure from science and logic when a substance is labeled 'cancer-causing' based on a response in a single animal study using high doses of a test material", she said.

Current views

Taken together, the complexity of the problem of assigning risk to this agent—the debate over assumptions concerning risks from early-in-life exposure, the principal role of a decomposition product rather than the agent itself in determining its long-term toxicity, the generation of that product both abiotically and through metabolism after consumption, as well as challenges in determining appropriate "subpopulations for study, representative parameters of the potency distribution, and corrections for bioassay length") On the other hand, representatives of the California Department of Health Services are on record as of 1991 stating that "the plausible estimates of risk, derived from conservative, reasonable assumptions, exceed those developed by EPA and NRDC".—supporting insignificant levels of "carcinogenicity of daminozide, alone or in combination with... 1,1-dimethylhydrazine".

As of 2005, daminozide remained classified as a probable human carcinogen by the EPA, and listed as a known carcinogen under California's Prop 65.