Case Study - Alliance for Risk Assessment

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37unique for the derivation of a 24-hr ReV is conducted. The same analytical steps used to deriveacute 1-hr ReVs and chronic ReVs (TCEQ 2012) are used to derive a 24-hr ReV. OECD (2010)also provides guidance applicable to the development of acute reference concentrations.Key StudiesBD has very low acute toxicity (TCEQ 2008). The toxicity of BD is shown in Figure C-1 as anexposure response array for acute (less than 24 hr) and subacute studies which were consideredfor the development of a 24-hr ReV. Effects in humans (slight smarting of the eyes and difficultyin focusing) occurred at 2000 ppm after a 7-hr BD exposure (Carpenter et al. 1944). Animalstudies show BD is a potential reproductive/developmental hazard to humans. The followingstudies were considered for the development of a 24-hr ReV:Developmental toxicity (decrease in maternal body weight gain and fetal body weight)occurs in mice, the most sensitive species, after BD exposure (6 hr/day, gestational day 6-15) with a lowest observed adverse effect level (LOAEL) of 200 ppm and a no-observedadverse effect level (NOAEL) of 40 ppm (Hackett et al. (1987b).In three different developmental studies in rats, the lowest critical effect is a decrease inbody weight parameters. Toxicity occurs in rats at much higher concentrations than inmice. The LOAELs in rat studies ranged from 1000-1500 ppm and the NOAELS rangedfrom 200-300 ppm (IISRP 1982; Hackett et al. 1987a; ACC 2003).After a 6-hr/day, 5-day exposure in male mice, decreased testes weight was observed(LOAEL = 500 ppm; NOAEL = 130 ppm). There was a concentration/duration effect onmale reproductive effects. After 4 weeks exposure in male mice, followed by mating,there was an increase in early fetal deaths with a LOAEL of 65 ppm. After 10 weeksexposure, a LOAEL of 12.5 ppm was observed for fetal deaths and sperm abnormalities.
difficulty focusing; Human; (E)DecBodyWeight; Rat; (F)DecBodyWeight; Rat; (G)DecBodyWeight; Rat; (A)DecBodyWeight; Mouse; (H)Dec Testes Wt; Mouse; (J)inc early fetal death; Mouse; (C)fetal deaths; abnormalities; Mouse;(B)Concentration (ppm)Key Study38Inhalation Exposure-Response ArrayTest Doses10,000NOAELBMCL1,000LOAEL10010Human------------------------ Rat--------------------Mice-------------------- Mice-----------------1-------------------------- Developmental Studies----------------------5-7 hrs 1 wk4 wk10 wkFigure C-1 BD Exposure response array for acute (less than 24 hr) and subacute studiesCitation Key Citation KeyACC (2003) A IISRP (1982) FAnderson et al. (1996) B Hackett et al. (1987a) GAnderson et al. (1998) C Hackett et al. (1987b) HCarpenter et al. (1944) E Pacchierotti et al. (1998) J38
Page 4: 1INTERPRETATION OF 24-HOUR SAMPLING
Page 7 and 8: 1,3-Butadiene concentration parts p
Page 9 and 10: 24-Hour Benzene Concentrations (ppb
Page 11 and 12: 8mortalityresponse relationship of
Page 13: 10Section 4 Twenty-Four Hour Refere
Page 17 and 18: 14Haber’s rule is dependent on th
Page 19 and 20: 161, which is considered to be cons
Page 21 and 22: 18Viluksela, M, Stahl, BU, Birnbaum
Page 23 and 24: 20Example 1: Development of a 24-Ho
Page 25 and 26: Log Concentration (µg/m 3 )22Total
Page 27 and 28: 24References1. Agency for Toxic Sub
Page 29 and 30: 26The TCEQ has historically develop
Page 31 and 32: 28Three subacute mouse studies iden
Page 33 and 34: 30higher than the multiple-day LOAE
Page 35 and 36: Log Concentration (µg/m 3 )32A UF
Page 37 and 38: 34This value is sufficiently conser
Page 39: 36Example 3: Development of a 24-Ho
Page 43 and 44: 40Figure 3-2 Schematic of BD Metabo
Page 45 and 46: 42Table 3-1: Derivation of the 1-Hr
Page 47 and 48: 1,3-Butadiene concentration parts p

Case Study - Alliance for Risk Assessment

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