Pa. Malsch et al., ESTIMATION OF A CHROMIUM INHALATION REFERENCE CONCENTRATION USING THEBENCHMARK DOSE METHOD - A CASE-STUDY, Regulatory toxicology and pharmacology, 20(1), 1994, pp. 58-82
The benchmark dose (BD) method has been proposed as an alternative to
the NOAEL/UF method for setting reference levels. The BD is the 95% lo
wer confidence limit on a dose corresponding to a 10% increase (or rel
ative change) in an adverse effect. A case study exploring the suitabi
lity of the current Cr(III) and Cr(VI) inhalation toxicity data bases
to the BD approach is presented. Because chromic acid mists, typical o
f many occupational Cr(VI) exposures, present a toxicological profile
different from that of Cr(VI) particulates, representative of environm
ental exposures, Cr(VI) particulate data were evaluated separately fro
m Cr(VI) acidic mist data. The current Cr(III) and Cr(VI) acidic mist
data bases proved inadequate for BD analysis due to data and/or study
quality limitations. Benchmark reference concentrations (RfCs) for par
ticulate Cr(VI) ranging from 0.34 mu g/m(3) (for lactate dehydrogenase
(LDH) in bronchoalveolar lavage fluid (BALF)) to 1.4 mu g/m(3) (for i
ncreased lung weights) are derived from data taken from U. Glaser et a
l. (Arch. Toxicol. 57, 250-256, 1985) and U. Glaser et al. (Environmen
tal Hygiene II, Springer-Verlag, Berlin/New York, 1990). A Cr(VI) part
iculate RfC of 0.34 mu g/m(3) based upon LDH in BALF as the critical e
ffect is proposed. This value may be viewed as conservative since it r
epresents the 95% lower confidence limit on the dose associated with a
10% increase in response for a sensitive endpoint and has appropriate
dosimetric adjustments and uncertainty factors incorporated. (C) 1994
Academic Press, Inc.