The sub-chronic toxicity in rats of isoparaffinic solvents

Carrillo, Juan-Carlos; Adenuga, David; McKee, Richard H.; Roth, Randy N.; Steup, David R.; Simpson, Bob

doi:10.1016/j.yrtph.2013.09.004

Cited by 16 publications

(17 citation statements)

References 48 publications

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“…3 for C9-C14 constituents. Recent publications (Adenuga et al 2014b, Carrillo et al 2013 provide support for this recommendation. It should be noted, however, that there is an ACGIH ® TLV ® of 1000 mg/m 3 for nonanes.…”

Section: Occupational Exposure Limitsmentioning

confidence: 82%

“…There are specific occupational exposure limits for n-hexane that are related to its neurological properties; for other aliphatic constituents of these solvents, occupational recommendations are set to avoid respiratory irritation and/or acute CNS effects. In repeated exposure studies, liver enlargement is commonly observed; male rat kidney effects associated with a2u-globulin induction are seen in studies of substances containing isoparaffinic and/or cycloparaffinic constituents, and small but statistically significant reductions in hematological parameters have been reported in some studies (Carrillo et al 2013, Carpenter et al 1975d, 1978, Galvin and Marashi 1999a, 1999b, 1999c, Kinkead et al 1985, Kim et al 2012, Malley et al 2000, Schreiner et al 1998, Sung et al 2010). As described above, liver enlargement without pathological changes or elevated levels of marker enzymes (ALT, AST) is considered to be an adaptive response rather than an adverse effect.…”

Section: Light Aliphatic Solvents (C5-c9)mentioning

confidence: 99%

“…The changes were not observed in kidneys of female rats or dogs. In studies to further characterize these effects, it was noted that these changes tended to be more commonly observed in studies of isoparaffinic hydrocarbons than in normal paraffinic or aromatic solvents (Carrillo et al 2013, Phillips and Egan 1984a, 1984b) and were referred to as "light hydrocarbon nephropathy" in some of the early publications. It was noted that the observations were similar to those described by Alden et al (1984) in a report of a study of decalin (a C10 cycloparaffin) in which the renal effects were associated with the induction of a specific urinary protein (a2u-globulin).…”

Section: Kidney Effectsmentioning

confidence: 99%

“…In some studies, small but statistically significant reductions in hematological parameters have been observed (Carrillo et al 2013). These changes, which are more commonly found in male than female rats, are characterized by reductions in hemoglobin content, packed cell volumes, and/or red blood cell (RBC) counts.…”

Section: Hematological Changesmentioning

confidence: 99%

“…The no observed adverse effect level was 7480 mg/m 3 (1571 ppm), the highest concentration tested. Carrillo et al (2013) summarized the results of a repeated inhalation study of a C8 isoparaffinic solvent. Rats were exposed 6 hours/day and 5 days/week to vapors at concentrations of 400 or 1200 ppm (approximately 1800 or 5500 mg/ m 3 ).…”

Section: Repeated Dose Studies Of C7-c9 Aliphatic Hydrocarbon Solventmentioning

confidence: 99%

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Characterization of the toxicological hazards of hydrocarbon solvents

McKee

Adenuga

Carrillo

2015

Critical Reviews in Toxicology

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Hydrocarbon solvents are liquid hydrocarbon fractions derived from petroleum processing streams, containing only carbon and hydrogen atoms, with carbon numbers ranging from approximately C5-C20 and boiling between approximately 35-370°C. Many of the hydrocarbon solvents have complex and variable compositions with constituents of 4 types, alkanes (normal paraffins, isoparaffins, and cycloparaffins) and aromatics (primarily alkylated one-and tworing species). Because of the compositional complexity, hydrocarbon solvents are now identified by a nomenclature ("the naming convention") that describes them in terms of physical/ chemical properties and compositional elements. Despite the compositional complexity, most hydrocarbon solvent constituents have similar toxicological properties, and the overall toxicological hazards can be characterized in generic terms. To facilitate hazard characterization, the solvents were divided into 9 groups (categories) of substances with similar physical and chemical properties. Hydrocarbon solvents can cause chemical pneumonitis if aspirated into the lung, and those that are volatile can cause acute CNS effects and/or ocular and respiratory irritation at exposure levels exceeding occupational recommendations. Otherwise, there are few toxicologically important effects. The exceptions, n-hexane and naphthalene, have unique toxicological properties, and those solvents containing constituents for which classification is required under the Globally Harmonized System (GHS) are differentiated by the substance names. Toxicological information from studies of representative substances was used to fulfill REACH registration requirements and to satisfy the needs of the OECD High Production Volume (HPV) initiative. As shown in the examples provided, the hazard characterization data can be used for hazard classification and for occupational exposure limit recommendations. Introduction Scope and purpose of the documentThe present document summarizes information on the physical/ chemical properties and toxicological hazards of hydrocarbon solvents and provides examples of the ways in which the information on hazard characterization can be used for hazard classification and to set occupational exposure limits. Many of the toxicological studies were published separately, but the results are summarized herein and referenced in the appendices.Hydrocarbon solvents are liquid hydrocarbon fractions that are primarily produced by the distillation of petroleum feed stocks or their synthetic analogs (e.g., Fischer-Tropsch derived materials), sometimes followed by additional processing steps such as solvent extraction, hydrodesulfurization, or hydrogenation. 1 Most hydrocarbon solvents are complex substances with variable compositions and are best described as UVCB 2 (unknown and variable composition) substances, but some are single constituent (mono-constituent) substances. The complex and variable nature of these solvents is the consequence of their manufacturing processes. In short, most hydroca...

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Section: Occupational Exposure Limitsmentioning

confidence: 82%

Section: Light Aliphatic Solvents (C5-c9)mentioning

confidence: 99%

Section: Kidney Effectsmentioning

confidence: 99%

Section: Hematological Changesmentioning

confidence: 99%

Section: Repeated Dose Studies Of C7-c9 Aliphatic Hydrocarbon Solventmentioning

confidence: 99%

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Characterization of the toxicological hazards of hydrocarbon solvents

McKee

Adenuga

Carrillo

2015

Critical Reviews in Toxicology

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Aliphatic Hydrocarbons

Rushton,

Kocabas,

Barranco

2023

Patty's Toxicology

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The aliphatic hydrocarbons discussed in this chapter are open‐chain compounds that may be saturated or unsaturated. The saturated compounds, known as paraffin hydrocarbons or alkanes, include methane and its homologs having the empirical formula C n H 2 n +2 . The unsaturated compounds fall into a number of homologous series: ( 1 ) those containing one double bond (ethene and its homologs) and having the formula C n H 2n are known as olefins or alkenes; ( 2 ) those containing one triple bond (acetylene and its homologs) are called acetylenes or alkynes and have the formula C n H 2 n −2 ; ( 3 ) those having two double bonds (allene, 1,3‐butadiene, and 1,4‐pentadiene represent three types) are diolefins or alkadienes and also have the formula C n H 2 n −2 ; ( 4 ) those having a large number of double or triple bonds or both double and triple bonds are named in analogous fashion as alkatrienes , alkatetraenes , alkadiynes , alkenynes , and alkadienynes . Aliphatic hydrocarbons have the potential to act as asphyxiants and central nervous system (CNS) depressants. Serious toxic effects of aliphatic hydrocarbons include asphyxia and chemical pneumonitis for many of the compounds in this category. There is evidence in humans of axonal neuropathy for n ‐hexane and cancer for 1,3‐butadiene. The hepatic and renal systems can be impacted by target organ toxicity, some of which may not be relevant to human.

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Trimethylpentan (alle Isomere) [MAK Value Documentation in German language, 2017]

Hartwig

2017

The MAK‐Collection for Occupational Health and Safety

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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated trimethylpentane (all isomers) [ 564‐02‐3 , 540‐84‐1 , 560‐21‐4 , 565‐75‐3 ] considering all toxicological endpoints. Available unpublished study reports and publications are described in detail. The re‐examination determined that it is difficult to draw final conclusions from a carcinogenicity study of a mixture of 542 hydrocarbons and from mechanistical studies with some of their single components. Thus, the assignment to Carcinogen Category 3 A has been withdrawn. The critical effect is the acute effect on the central nervous system in rats. The NOAEC after 60 min inhalation is 500 ml 2,2,4‐trimethylpentane/m 3 . Experimental data from structurally analogous n‐alkanes and iso‐alkanes lead to the assumption that the concentration of 2,2,4‐trimethylpentane in the brain after 8 hours will be about twice as high as after one hour. The short half‐life in the brain, estimated to be about one hour, does not predict an accumulation during the work week. The same assumptions are made for the other trimethylpentane isomers. Thus, taking into consideration uncertainties in the extrapolation of animal to human data, a MAK value of 100 ml/m 3 (470 mg/m 3 ) is set for all trimethylpentane isomers. As the critical effect is systemic, trimethylpentane isomers are assigned to Peak Limitation Category II. The excursion factor of 2 is set as the estimated half‐life in the brain is one hour. Prenatal developmental toxicity studies with trimethylpentane isomers are not available. For structurally analogous C8‐isoalkanes the NOAEC for developmental toxicity in rats is more than 1200 ml/m 3 . Acute neurotoxicity is critical, but the consequences of acute neurotoxic effects on in‐utero development of the nervous system are not known and studies on developmental neurotoxicity of C8‐alkanes are not available. Thus, trimethylpentane isomers are classified in Pregnancy Risk Group D. There are no clinical data and no data in animals concerning the sensitizing potential of trimethylpentane isomers. In analogy to n‐heptane, skin contact is not expected to contribute significantly to systemic toxicity.

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The sub-chronic toxicity in rats of isoparaffinic solvents

Cited by 16 publications

References 48 publications

Characterization of the toxicological hazards of hydrocarbon solvents

Characterization of the toxicological hazards of hydrocarbon solvents

Aliphatic Hydrocarbons

Trimethylpentan (alle Isomere) [MAK Value Documentation in German language, 2017]

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