Dose-Response Modelling of Growth for Developmental Toxicity

Chen, James J.; Gaylor, David W.; LaBorde, James B.

doi:10.1002/(sici)1099-095x(199603)7:2<135::aid-env163>3.0.co;2-i

Cited by 5 publications

(2 citation statements)

References 18 publications

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“…The least squares means allow comparisons that account for differences in litter size and sex. The mathematical model was based on an article by Chen et al 36 Statistical significance of differences from control was recognized at the 5% or 1% 2-sided levels.…”

Section: Prenatal Developmental Toxicity Testmentioning

confidence: 99%

The Toxicological Properties of Petroleum Gases

McKee

Herron²,

Saperstein³

et al. 2013

Int J Toxicol

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To characterize the toxicological hazards of petroleum gases, 90-day inhalation toxicity (Organization for Economic Cooperation and Development [OECD] 413) and developmental toxicity (OECD 414) tests were conducted with liquefied propane gas (LPG) at concentrations of 1000, 5000, or 10 000 ppm. A micronucleus test (OECD 474) of LPG was also conducted. No systemic or developmental effects were observed; the overall no observed adverse effect concentration (NOAEC) was 10 000 ppm. Further, there was no effect of LPG exposure at levels up to 10 000 ppm on micronucleus induction and no evidence of bone marrow toxicity. Other alkane gases (ethane, propane, n-butane, and isobutane) were then evaluated in combined repeated exposure studies with reproduction/development toxicity screening tests (OECD 422). There were no toxicologically important changes in parameters relating to systemic toxicity or neurotoxicity for any of these gases at concentrations ranging from 9000 to 16 000 ppm. There was no evidence of effects on developmental or reproductive toxicity in the studies of ethane, propane, or n-butane at the highest concentrations tested. However, there was a reduction in mating in the high-exposure group (9000 ppm) of the isobutane study, which although not significantly different was outside the range previously observed in the testing laboratory. Assuming the reduction in mating to have been toxicologically significant, the NOAEC for the isobutane reproductive toxicity screening test was 3000 ppm (7125 mg/m 3 ). A method is proposed by which the toxicity of any of the 106 complex petroleum gas streams can be estimated from its composition.

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Section: Prenatal Developmental Toxicity Testmentioning

confidence: 99%

The Toxicological Properties of Petroleum Gases

McKee

Herron²,

Saperstein³

et al. 2013

Int J Toxicol

View full text Add to dashboard Cite

show abstract

“…The dose-response trials are common in biological, environmental, toxicological, and pharmacological studies (Chen, Gaylor, & Laborde, 1998;Finney, 1978;Piegorsch & Bailer, 1997). In this paper, we consider a dose-mortality trial where the ith group of n i subjects are exposed to a drug of amount x i for a specified period of time, i = 1, .…”

Section: Introductionmentioning

confidence: 99%

Methods of finding the initial values of parameters in the maximum likelihood estimating equations for a logistic regression model and comparison of their final solutions using different criterion functions

Ghosh

Banerjee

2010

Journal of the Korean Statistical Society

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a b s t r a c tWe present two methods of finding the initial values of parameters of the maximum likelihood estimating equations (MLEE) for a logistic regression model using two criterion functions. We then use the initial values and the corresponding criterion functions to obtain the final solutions of MLEE. Most experiments include more than two doses for determining a lethal dose like ED 50 . With more than two doses, we do not have an exact analytical expression for the solution of estimating equations. However, for two doses, we do have an exact analytic expression for the solution of estimating equations. The iterative methods make use of the initial values of the parameters. We have used the search algorithm for performing the optimization to find the final solutions of MLEE. The proposed approach starts with all possible pairs of doses from the doses considered in the experiment. It then chooses the pair giving the optimum value of a criterion function and the corresponding exact solutions for the parameters based on two observations in the pair as the initial values of parameters for solving MLEE for all observations. The proposed methods are transparent in the selection of the initial values of parameters. The proposed methods are computer intensive like bootstrap and jackknife methods popular among statisticians. We illustrate our two methods of finding the initial values with an observed beetle mortality data. We then apply them to obtain the final solutions using two criterion functions. We observe that the numerical values of ED 50 for the initial values of the parameters obtained by our approach are almost the same as the numerical values of ED 50 for the final solutions. This closeness of the estimated ED 50 values from our initial parameter values to the estimated ED 50 values from the final solutions is a strong feature of our proposed methods. Moreover, the proposed methods compare favorably with SAS and R in terms of CPU time values.

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

Roberts

Gray

Trimmer

et al. 2014

Regulatory Toxicology and Pharmacology

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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.

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Dose-Response Modelling of Growth for Developmental Toxicity

Cited by 5 publications

References 18 publications

The Toxicological Properties of Petroleum Gases

The Toxicological Properties of Petroleum Gases

Methods of finding the initial values of parameters in the maximum likelihood estimating equations for a logistic regression model and comparison of their final solutions using different criterion functions

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

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