Hormesis: Calabrese Responds

In his commentary in Environmental Health Perspectives, Calabrese (2009) offered a num­ ber of responses to my critique of hormesis methodology (Mushak 2009). Here I will provide a counterpoint to that effort. • Calabrese (2009) falsely asserted that I erred in calculations associated with entry and evaluatory criteria for hormesis frequency, specifically by choosing the wrong denomi­ nator for examining the proportion of entry candidates eventually found to be hormetic using the most conventional form of statis­ tical significance. The choice of a denomi­ nator for these calculations depends on the question asked. My key question was, What proportions of 668 dose–response entry candidates from 20,285 original arti­ cles, using the three criteria identified by Calabrese and Baldwin (2001), partition into each of three hormesis categories? A total of 245 of the 668 candidate dose– responses (37%) had hormetic character, but only 74 of those (30%) were derived using the typical statistical significance test, yielding 11% overall. • Calabrese (2009) mis charac terized my statements about the reliability of the two unvali dated selection criteria (Mushak 2009). My comments addressed applying criteria to screening large databases of pub­ lications for a putative new phenomenon. I was not concerned about routine uses of statistical forms for empirical data (e.g., analyses using 95% confidence intervals on independent means). • Calabrese (2009) misunderstood my con­ cerns about the two tallies of dosing points (1,089 and 1,791 points) from two of his previous studies (Calabrese and Baldwin 2001, 2003b). The still unanswered ques­ tion is how the 871 (80% of 1,089) control­equivalent and threshold response– compatible dosing points reported by Calabrese and Baldwin (2001) are mathe­ matically incorporated into a high pre­ ponderance of hormetic dosing points (to a 2.5:1 ratio) they reported later (Calabrese and Baldwin 2003b). I was not concerned about simple counts. • Calabrese mis interpreted my concern about clustered distributions in entry candidates in the 20,285 articles. I was not referring to publications in which the same informa­ tion is recapitulated in multiple articles, but whether serial publications that described a given experimental approach but tested different substances were included in the articles database. The clustering pattern, although important, remains unexplained. • Calabrese stated that the use of entry and evaluation criteria had been validated for both sensitivity and specificity. The ques­ tion here is whether entry and evaluation criteria that established the original sets of hormetic, false­positive, and false­negative …