Estimated reference dose

Selection of the Key Study. The available toxicity data for sulfur mustard are summarized in Table 13 The experimental study considered most suitable 

Sasser et al. (1989a) Rat subchronic 0.1 0.3 Epithelial hyperplasia of the forestomach 

Sasser et al. (1989b) Rat two-generation — 0.03 Maternal toxicity acanthosis and hyperplasia of the forestomach 

no-observed-adverse-effect level LOAEL, lowest-observed-adverse-effect level. 

The lowest dose tested, 0.03 mg kg d , can be considered a LOAEL for rats subchronically exposed to sulfur mustard, with epithelial acanthosis and hyperplasia of the forestomach as the critical effect. Using this LOAEL, a human chronic RfDg can be derived by adjusting the dose to a 7 d/wk exposure protocol and then applying the result to the RfD methodology. Dose adjustments for discontinuous exposure can be made as follows female rats were gavaged five times per week for 15 wk (75 d), total dose = 2.25 mg/kg daily for 3 wk (21 d), total dose = 0.63 mg/kg and four times per week for 3 wk (12 d), total dose = 0.36 mg/kg. The combined total dose over the 21-wk exposure period, therefore, was 3.24 mg/kg dividing the combined total dose of 3.24 mg/kg by 147 d (21 wk) results in an adjusted LOAEL of 0.022 mg kg d . The adjusted LOAEL can then be applied to the equation for the derivation of an RfD. 

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TABLE 6.6. Estimated reference doses (RfDg), RfD uncertainty factors, and health-based environmental... 

Table 5. Estimated reference doses (RfDs)a and reference concentrations (RfCs) for agent VX degradation and related products6...

Epididymis—testicular structure in which spermatozoa are stored Epithelium—cells covering the internal and external surfaces of the body Erythema—redness of the skin produced by congestion of the capillaries Estimated Reference Dose (RfDe)—toxicity value calculated in this report from the available toxicological data but not yet verified by EPA (see Reference Dose)... 

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