Toxicological Assessment of Heavy Straight Run Naphtha in a Repeated Dose/Reproductive Toxicity Screening Test

McKee, Richard H.; Steup, David R.; Schreiner, Ceinwen A.; Podhasky, Paula; Malley, Linda A.; Roberts, Linda G.

doi:10.1177/1091581813504224

Cited by 6 publications

(2 citation statements)

References 37 publications

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“…The thyroid, liver, and pituitary changes are characteristics of a consequence of hepatocellular induction as a result of enhanced hepatic metabolism. 29 As a side effect of hepatic induction, an increased liver metabolism of thyroid hormones T3 and T4 can occur. This subsequently leads to an enhanced thyroid gland production of these hormones, resulting in a negative feedback stimulation of TSH production.…”

Section: Parental Toxicitymentioning

confidence: 99%

Toxicological Assessment of Higher Olefins in OECD TG 422 Repeated Dose and Reproductive /Developmental Toxicity Screening Tests in Han Wistar Rats

Shi,

Carrillo,

Penman

et al. 2023

Int J Toxicol

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Higher olefins (HO) are used primarily as intermediates in the production of other chemicals, such as polymers, fatty acids, plasticizer alcohols, surfactants, lubricants, amine oxides, and detergent alcohols. The potential toxicity of five HO (i.e., 1-Octene, Nonene, Decene, Hexadecene, and 1-Octadecene) with carbon ranging from C8 to C18 was examined in a combined repeated dose and reproduction/developmental toxicity screening study (OECD TG 422). These five HO were administered to Han Wistar rats by gavage at 0 (controls), 100, 300, and 1000 mg/kg bw/day. As a group of substances, adaptive changes in the liver (liver weight increase without pathological evidence), as well as increased kidney weight in male rats, were observed in HO with carbon numbers from C8 to C10. The overall systemic no observed adverse effect level (NOAEL) for all HO was determined at 1000 mg/kg bw/day. In the reproductive/developmental toxicity assessment, offspring viability, size, and weights were reduced in litters from females treated with Nonene at 1000 mg/kg bw/day. The overall no observed effects level (NOEL) for reproductive toxicity was considered to be 300 mg/kg bw/day for Nonene and 1000 mg/kg bw/day for the other four HO, respectively. These data significantly enrich the database on the toxicity of linear and branched HO, allowing comparison with similar data published on a range of linear and branched HO. Comparisons between structural class and study outcome provide further supportive data in order to validate the read-across hypothesis as part of an overall holistic testing strategy.

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Section: Parental Toxicitymentioning

confidence: 99%

Toxicological Assessment of Higher Olefins in OECD TG 422 Repeated Dose and Reproductive /Developmental Toxicity Screening Tests in Han Wistar Rats

Shi,

Carrillo,

Penman

et al. 2023

Int J Toxicol

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“…As no hazards were identified that differed from previously published results of either naphtha streams or formulated gasoline, it was concluded that the hazards of all naphthas fall within the range of substances tested and that further toxicological testing for hazard characterization is unnecessary. 51 Benzene, when present, must be taken into account and, in particular, the occupational exposure recommendations for benzene must be observed. Finally, with respect to risk assessment, it should be noted that naphthas may have relatively wide boiling ranges and that exposures are primarily to the more volatile C 4 -C 6 constituents.…”

Section: Characterization Of Toxicological Hazard Information For Majmentioning

confidence: 99%

The Mammalian Toxicological Hazards of Petroleum-Derived Substances

McKee

White

2013

Int J Toxicol

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Petroleum-derived substances are complex and composed of aliphatic (normal-, iso-, and cycloparaffins), olefinic, and/or aromatic constituents. Approximately 400 of these complex substances were evaluated as part of the US Environmental Protection Agency voluntary High Production Volume (HPV) Challenge program. The substances were separated into 13 groups (categories), and all available data were assessed. Toxicology testing was conducted as necessary to fully address the end points encompassed by the HPV initiative. In a broad sense, volatile hydrocarbons may cause acute central nervous system effects, and those that are liquids at room temperature pose aspiration hazards if taken into the lungs as liquids and may also cause skin irritation. Higher boiling substances may contain polycyclic aromatic constituents (PACs) that can be mutagenic and carcinogenic and may also cause developmental effects. Substances containing PACs can also cause target organ and developmental effects. The effects of aliphatic constituents include liver enlargement and/or renal effects in male rats via an a-2u-globulin-mediated process and, in some cases, small but statistically significant reductions in hematological parameters. Crude oils may contain other constituents, particularly sulfur-and nitrogen-containing compounds, which are removed during refining. Aside from these more generic considerations, some specific petroleum substances may contain unusually toxic constituents including benzene, 1,3-butadiene, and/or n-hexane, which should also be taken into account if present at toxicologically relevant levels.

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Assessment of petroleum streams for thyroid toxicity

Fowles¹,

Banton

Boogaard

et al. 2016

Toxicology Letters

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The thyroid gland, and its associated endocrine hormones, is a growing area of interest in regulatory toxicology due to its important role in metabolism, growth and development. This report presents a review of the toxicology data on chemically complex petroleum streams for thyroid hormone effects. Toxicological summaries and studies from all available published and un-published sources were considered, drawing upon the European REACH regulatory submissions for 19 petroleum streams, with in depth review of 11 individual study reports and 31 published papers on related products or environmental settings. Findings relevant to thyroid pathology or thyroid hormone homeostasis were specifically sought, summarized, and discussed. A total of 349 studies of 28-days or longer duration were considered in the review, including data on mice, rats, rabbits, dogs, humans, and fish. The thyroid was almost invariably not a target organ in these studies. Three rodent studies did find thyroid effects; one on a jet fuel product (JP-8), and two studies on a heavy fuel oil product (F-179). The JP-8 product differs from other fuels due to the presence of additives, and the finding of reduced T4 levels in mice in the study occurred at a dose that is above that expected to occur in environmental settings (e.g. 2000mg/kg). The finding for F-179 involved thyroid inflammation at 10-55mg/kg that co-occurred with liver pathology in rats, indicating a possible secondary effect with questionable relevance to humans. In the few cases where findings did occur, the polycyclic aromatic hydrocarbon (PAH) content was higher than in related substances, and, in support of one possible adverse outcome pathway, one in-vitro study reported reduced thyroid peroxidase (TPO) activity with exposure to some PAH compounds (pyrene, benzo(k)fluoranthene, and benzo(e)pyrene). However, it could not be determined from the data available for this review, whether these specific PAH compounds were substantially higher in the JP-8 or F-179 products than in studies in which thyroid effects were not observed. Thus, a few products may carry a weak potential to affect the thyroid at high doses in rodents, possibly through secondary effects on the rodent liver or possibly through a pathway involving the inhibition of TPO by specific members of the PAH family. Human epidemiology evidence found weak and inconsistent effects on the thyroid but without identification of specific chemicals involved. Two studies in petroleum workers, which found a lower rate of morbidity and mortality overall, reported a statistically significant increase in thyroid cancer, but the small number of cases could not exclude confounding variables as possible explanations for the statistical findings. Overall, the available data indicates a low potential for thyroid hormone effects from exposure to petroleum streams, especially when the aromatic content is low. Because regulatory studies for most chemicals do not include detailed thyroid function or receptor studies, it remains possible that subclinic...

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Toxicological Assessment of Heavy Straight Run Naphtha in a Repeated Dose/Reproductive Toxicity Screening Test

Cited by 6 publications

References 37 publications

Toxicological Assessment of Higher Olefins in OECD TG 422 Repeated Dose and Reproductive /Developmental Toxicity Screening Tests in Han Wistar Rats

Toxicological Assessment of Higher Olefins in OECD TG 422 Repeated Dose and Reproductive /Developmental Toxicity Screening Tests in Han Wistar Rats

The Mammalian Toxicological Hazards of Petroleum-Derived Substances

Assessment of petroleum streams for thyroid toxicity

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