Health assessment of gasoline and fuel oxygenate vapors: Developmental toxicity in rats

Abstract

Gasoline-vapor condensate (BGVC) or condensed vapors from gasoline blended with methyl t-butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME) diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for developmental toxicity in Sprague-Dawley rats exposed via inhalation on gestation days (GD) 5-20 for 6h/day at levels of 0 (control filtered air), 2000, 10,000, and 20,000mg/m(3). These exposure durations and levels substantially exceed typical consumer exposure during refueling (<1-7mg/m(3), 5min). Dose responsive maternal effects were reduced maternal body weight and/or weight change, and/or reduced food consumption. No significant malformations were seen in any study. Developmental effects occurred at 20,000mg/m(3) of G/TAME (reduced fetal body weight, increased incidence of stunted fetuses), G/TBA (reduced fetal body weight, increased skeletal variants) and G/DIPE (reduced fetal weight) resulting in developmental NOAEL of 10,000mg/m(3) for these materials. Developmental NOAELs for other materials were 20,000mg/m(3) as no developmental toxicity was induced in those studies. Developmental NOAELs were equal to or greater than the concurrent maternal NOAELs which ranged from 2000 to 20,000mg/m(3). There were no clear cut differences in developmental toxicity between vapors of gasoline and gasoline blended with the ether or alcohol oxygenates.

Diesel Oil Vapor Inhalation: Risk Factor for Heart Attack

“…The health endpoints include assessments for standard subchronic toxicity, neurotoxicity, genotoxicity, immunotoxicity, developmental and reproductive toxicity, and chronic toxicity/ carcinogenicity. The results of chronic toxicity testing of gasoline and gasoline combined with MTBE have already been reported [5] and reported elsewhere in this issue are the findings for genotoxicity [6], neurotoxicity [7], immunotoxicity [8], reproductive toxicity [9], and developmental toxicity testing in mice and rats [10], [11]. Key differences between whole gasoline and the vaporized gasoline are the significantly greater concentration of C4 and C5 constituents and depletion of C7-C12 aromatic constituents in the vapor condensate.…”

Health assessment of gasoline and fuel oxygenate vapors: Reproductive toxicity assessment

“…The health endpoints include assessments for standard subchronic toxicity, neurotoxicity, genotoxicity, immunotoxicity, developmental and reproductive toxicity, and chronic toxicity/carcinogenicity. The results of chronic toxicity testing of gasoline and gasoline combined with MTBE have already been reported ( Benson et al, 2011 ) and reported elsewhere in this issue are the findings for subchronic toxicity testing ( Clark et al, 2014 ), genotoxicity ( Schreiner et al., 2014 ), neurotoxicity ( O'Callaghan et al., 2014 ), immunotoxicity ( White et al, 2014 ) and developmental toxicity testing in mice and rats ( Roberts et al, 2014a , b ). This paper describes the results of reproductive toxicity tests performed separately and submitted to EPA.…”

“…Developmental NOAELs were 20,000 mg/m 3 for BGVC, G/MTBE, G/ETBE, G/EtOH and G/DIPE. For G/TAME and G/TBA, developmental NOAELs were 10,000 mg/m 3 due to decreased fetal body weight and increased incidence of stunted fetuses at 20,000 mg/m 3 in the G/TAME study, and increased skeletal variations, possibly related to maternal stress (decreased body weight gain and food consumption) at 20,000 mg/m 3 in the G/TBA study ( Roberts et al, 2014b ). Developmental studies at the same doses performed with BGVC and G/MTBE only in pregnant mice in which exposure lasted from GD5–17 resulted in developmental NOAEL values of 2000 and 20,000 mg/m 3 , respectively ( Roberts et al, 2014a ).…”

Introduction: Gasoline health effects and risk management

“…Developmental Toxicity in Rats -evaluated the maternal and developmental toxicity in Sprague-Dawley rats of gasoline and gasoline blended with six different oxygenates (Roberts et al, 2014b).…”