Developmental Toxicity Study of Clarified Slurry Oil (CSO) in the Rat

Hoberman, Alan M.; Christian, Mildred S.; Lovre, Stanton C.; Roth, Randy N.; Koschier, Francis J.

doi:10.1093/toxsci/28.1.34

Cited by 4 publications

(6 citation statements)

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“…In addition, in repeated dose studies with both GTL naphtha and GTL base oil, no histopathological changes were observed in either male or female reproductive organs. Again, this is in line with the observation for conventional petroleum-derived products that prenatal developmental toxicity as observed with some products, such as heavy fuel oils, is related to the concentration of 4-to 6-ring polycyclic aromatic constituents (Feuston et al 1994;Hoberman et al 1995a;. Since GTL products are virtually devoid of aromatic constituents, prenatal developmental toxicity was not expected to occur which was confirmed by the studies conducted.…”

Section: Repeated-dose Studiessupporting

confidence: 86%

“…Since GTL products are virtually devoid of aromatic constituents, prenatal developmental toxicity was not expected to occur which was confirmed by the studies conducted. Fertility is not an issue with conventional petroleum-derived products, even with products with high concentrations of polycyclic aromatic constituents (Hoberman et al 1995b;. Hence, it is not surprising that GTL products, which consist entirely of saturated hydrocarbons, have no effect on fertility either.…”

Section: Repeated-dose Studiesmentioning

confidence: 99%

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Toxicological and ecotoxicological properties of gas-to-liquid (GTL) products. 1. Mammalian toxicology

Boogaard

Carrillo

Roberts

et al. 2016

Critical Reviews in Toxicology

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Gas-to-liquid (GTL) products are synthetic hydrocarbons produced from natural gas using a Fischer-Tropsch process. This process yields a synthetic crude oil that consists of saturated hydrocarbons, primarily linear alkanes, with increasing amounts of branched (methyl-groups) alkanes as the chains get longer. In addition, small amounts of cycloalkanes (branched cyclopentanes and cyclohexanes) may be formed as the polymerization reaction prolongs. This synthetic crude can subsequently be refined to a range of products very similar to petroleum refining. However, in contrast to their petroleum-derived analogs, GTL products are essentially free of unsaturated or aromatic constituents and also no sulfur-, oxygen-, or nitrogen-containing constituents are present. From a regulatory perspective, GTL products are new substances which require extensive testing to assess their hazardous properties. As a consequence, a wide range of GTL products, covering the entire portfolio of GTL products, have been tested over the past few years in a wide variety of toxicological studies, including reproductive and prenatal development toxicity studies. This review provides an overview of the hazardous properties of the various GTL products. In general, the data collected on GTL products provide strong proof that they exert minimal health effects. In addition, these data provide supporting evidence for what is known on the mechanisms of mammalian toxicology of their petroleum-derived analogs. In the few cases where adverse effects were found for the GTL substances, these were usually less severe than the adverse effects observed with their petroleum-derived analogs.

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Section: Repeated-dose Studiessupporting

confidence: 86%

Section: Repeated-dose Studiesmentioning

confidence: 99%

Toxicological and ecotoxicological properties of gas-to-liquid (GTL) products. 1. Mammalian toxicology

Boogaard

Carrillo

Roberts

et al. 2016

Critical Reviews in Toxicology

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“…When samples of CSO are tested in developmental toxicity studies, they typically produce developmental effects (resorptions, reduced fetal body weight, and cleft palate) at levels below 5 mg/kg/d. 42,43 In contrast, in screening studies to assess the potential for CSO to affect male and female reproductive parameters, 44 there were no effects at levels up to 250 mg/kg/d, the highest dose tested.…”

Section: Reproductive Toxicitymentioning

confidence: 88%

Subchronic and Developmental Toxicity of Aromatic Extracts

Dalbey¹,

McKee

Goyak

et al. 2014

Int J Toxicol

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Aromatic extracts (AEs; distillate AEs [DAEs] and residual AEs [RAEs]) are complex, highly viscous liquid petroleum streams with variable compositions derived by extraction of aromatic compounds from distillate and residual petroleum fractions from a vacuum distillation tower, respectively. The DAEs generally contain significant amounts of polycyclic aromatic compounds (PACs) and are carcinogenic. The RAEs typically contain lower concentrations of biologically active PACs. The PACs in refinery streams can cause effects in repeated-dose and developmental toxicity studies. In a 13-week dermal study, light paraffinic DAE had several dose-related effects involving multiple organs; no-observed-effect level was <5 mg/kg/d, with no overt toxicity. Predicted dose-responses at 10% (PDR10s), modeled doses causing a 10% effect on sensitive end points based on PAC content, ranged from 25 to 78 mg/kg/d for untested paraffinic DAEs. The no observed adverse effect level (NOAEL) for developmental toxicity for light paraffinic DAE was 5 mg/kg/d. Statistically significant developmental effects at higher doses were associated with maternal effects. The PDR10s for developmental toxicity of paraffinic DAEs ranged from 7 to >2000 mg/kg/d, reflecting differences due to variation in PACs. The NOAELs for RAEs were 500 mg/kg for 90-day studies and 2000 mg/kg for developmental toxicity. Reproductive toxicity is not considered to be a sensitive end point for AEs based on the toxicity tests with DAEs, RAEs, and other PAC-containing petroleum substances. In vivo micronucleus tests on heavy paraffinic DAE, RAEs, and a range of other petroleum substances have been negative. The exception to this general trend was a marginally positive response with light paraffinic DAE. Most DAEs are considered unlikely to produce chromosomal effects in vivo.

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“…Recently, it has been reported by the petroleum industry that dermal treatment of pregnant Sprague‐Dawley rats with a particular refined oil product produces embryolethality in the offspring [5,6]. Because these refined oil products are complex hydrocarbon mixtures, it is difficult to identify which chemical entity or mixture of chemicals may be producing or contributing to this lethality.…”

Section: Introductionmentioning

confidence: 99%

“…The doses were derived from results observed in a developmental toxicity study [8] of carbon black oil and administered percutaneously. Results of their study indicate that maternal weight gain and food consumption were significantly decreased in pregnant females exposed to 50 mg/kg/day (equivalent to 2.5 mg/kg/day carbazole and total benzocarbazole each) crude oil.…”

Section: Introductionmentioning

confidence: 99%

Comparative developmental dermal toxicity and mutagenicity of carbazole and benzo[a]carbazole

Dutson

Booth

Schaalje³

et al. 1997

Enviro Toxic and Chemistry

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Abstract-The objectives of this study were (1) to determine the developmental toxicity of carbazole and benzo [a]carbazole following daily dermal administration to female Sprague-Dawley rats on days 0 through 20 of gestation and (2) to determine the mutagenicity of these two compounds using a modified version of the Ames assay. These chemicals are of concern because they are found in a variety of environmental matrices including crude oil mixtures. No signs of maternal or developmental toxicity were considered to be related to dermal administration of carbazole at doses of 2.5, 25.0, and 250.0 mg/kg. Signs of maternal toxicity considered to be related to administration of benzo [a]carbazole included significantly decreased body-weight gain and decreased absolute-food consumption at a dose of 250.0 mg/kg. Signs of developmental toxicity considered to be related to administration of benzo [a]carbazole included significantly decreased number of total (live and dead combined) and live pups on lactation day 0 as well as significantly decreased average pup weight on lactation days 0 and 4 at a dose of 250.0 mg/kg. Because developmental toxicity following benzo[a]carbazole treatment was observed only at a dose at which maternal toxicity was observed, it is likely that the effects on the offspring are secondary to the treatment effects on the dam. Evidence of toxic effects with benzo[a]carbazole in the absence of effects with carbazole suggests that the substituted benzene ring enhances the biological activity of this compound. Carbazole was nonmutagenic with or without S-9 activation, whereas benzo[a]carbazole showed a clear dose-response with S-9 activation. Without S-9 activation, benzo[a]carbazole was nonmutagenic. Apparently benzo[a]carbazole must be enzymatically activated in order to be mutagenic.

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Developmental Toxicity Study of Clarified Slurry Oil (CSO) in the Rat

Cited by 4 publications

References 0 publications

Toxicological and ecotoxicological properties of gas-to-liquid (GTL) products. 1. Mammalian toxicology

Toxicological and ecotoxicological properties of gas-to-liquid (GTL) products. 1. Mammalian toxicology

Subchronic and Developmental Toxicity of Aromatic Extracts

Comparative developmental dermal toxicity and mutagenicity of carbazole and benzo[a]carbazole

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