Cover Image


View/Hide Left Panel
4. Consequences of unusually large intake or chronic cumulative use

There may be adverse effects associated with consumption of excessively large amounts of chaparral (Heron and Yarnell, 2001). This type of overuse is typically related to encapsulated chaparral products.

B. Animal Studies

Animal studies on chaparral: There were no animal studies identified that showed liver toxicity as the result of chaparral administration. In studies with rats, significant toxic effects were demonstrated following administration of chaparral; however, the nature of the toxicity was not documented (Nakazato et al., 1998; Ulreich et al., 1997). The ethanol:water tincture of chaparral administered to the rats was lethal in the relatively large amounts administered in these studies. In all, there is evidence of considerable toxic effects from four different animal models: using rats (Konno et al., 1987; Nakazato et al., 1998; Ulreich et al., 1997), hamsters (Granados and Cardenas, 1994), chickens (Zamora, 1984), and insects (Mabry et al., 1977) with relatively high exposures to chaparral. In considering all of the animal studies (Table E), the evidence evaluating any aspects of the safety of chaparral in animal studies is minimal.

Acute studies on NDGA in animals: The evidence evaluating the safety of NDGA, a major component of chaparral, is more substantial but is still incomplete (Table E). NDGA administered by gavage to rats and mice was reported to have an LD50 of > 4 g/kg body weight. NDGA was somewhat more toxic in guinea pigs, with an LD50 of 0.8 g/kg body weight. Thus, the LD50 is less than 100× a typical human intake.

Chronic studies on NDGA in animals: Chronic studies on the safety of NDGA are limited to toxicity studies conducted primarily in small rodents (Table E). Rats fed NDGA at 0.5 percent of their diet exhibited massive hemorrhages and multiple renal cysts in experiments reported only in abstract (Cranston et al., 1947) and reviews (Lehman et al., 1951). Strong evidence has been published that NDGA fed to rats at high doses (1 or 2 percent of the diet) clearly leads to various pathological changes. In various rat models, growth inhibition and structural changes in or near the kidney have been shown to develop within 2 to 6 months (Cranston et al., 1947; Gardner et al., 1986, 1987; Lehman et al., 1951). Renal and mesenteric cysts form within 6 to 12 months of NDGA feeding (Goodman et al., 1970; Grice et al., 1968; Lehman et al., 1951). By 18 months of feeding 1 percent NDGA (Grice et al., 1968) or 6 months of feeding 2 percent NDGA (Evan and Gardner, 1979), the development of renal and mesenteric cysts is profound. The renal cysts contained degenerating tubular cells and the renal

The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement