Development of an Acceptable Factor To Estimate Chronic End Points From Acute Toxicity Data

Abstract

Acceptable daily intake (ADI) values are routinely developed for threshold toxicants from NOAELs determined from human or animal chronic or subchronic data. These NOAELs are then divided by appropriate uncertainty factors ranging from 10 to 1000 depending on the quality of the data. However, for the vast majority of chemicals used industrially, adequate toxicity data needed to use this process are not available. Thus, a procedure to estimate a chronic toxicity endpoint from acute toxicity data, such as an oral rat LD50, becomes necessary. An acute-to-chronic application factor of 0.0001 was developed, which when multiplied by an oral LD50 for an individual chemical, yields a surrogate chronic NOAEL. This figure can then be used to estimate an acceptable daily exposure for humans. The process used to estimate this application factor is detailed.

Subacute toxicity study in Wistar rats fed with StemEnhanceTM, an extract from Aphanizomenon flos-aquae

“…[23][24][25][26][27] Our studies demonstrated that feeding StemEnhance at 600 mg/kg for 2 weeks was not toxic to Wistar rats. StemEnhance did not affect the behavior or physical examinations of the rats.…”

Allowable limits for toxic leachables: practical use of ISO 10993-17 standard * *The recommendations offered in this chapter should not be construed as guidance from the US Food and Drug Administration (FDA). The mention of commercial products, their sources or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services.

“…Venman and Flaga (1985) compared oral LD50 values for compounds to their respective NOAEL values from long-term repeat-dose studies. Since the LD50 value represents a dose consistent with a very severe endpoint, it is understandable that a MF much greater than that applied to a NOAEL value should be used when deriving a TI based on an LD50 value rather than a NOAEL value.…”

Assessing Human Health Response in Life Cycle Assessment Using ED10s and DALYs: Part 2—Noncancer Effects

“…To hedge against the tendency to neglect chemicals that have been incompletely tested (Gray, Brand, & Evans, 1997), we explore the potential for estimating a potency factor from a more readily available acute toxicity measure. Venman and Flaga (1985) and Layton et al (1987), for example, suggested that readily available lethal dose data could provide a basis for estimating measures such as the effect dose ED 10h .…”