The Relationship Among Microsomal Enzyme Induction, Liver Weight and Histological Change in Rat Toxicology Studies

Amacher, David E.; Schomaker, Shelli; Burkhardt, John E.

doi:10.1016/s0278-6915(98)00066-0

Cited by 104 publications

(59 citation statements)

References 20 publications

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“…The reduction in body weight gains may be due to the combined action of cholinergic and oxidative stress [19,[34][35][36][37] and/or due to the increased degradation of lipids and proteins as a direct effect of organophosphate compound exposure [38]. Moreover, the increase in liver weight could be attributed to the relationship between liver weight increase and various toxicological effects or to the reduction in body weight gain of experimental animals [2,34,36,[39][40][41]. However, co-administration with SAC or VC attenuated the statistical different change of body and relative liver weights in DM-treated animals.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of a Synthetic Antioxidant “Acetyl Gallate Derivative” Against Dimethoate Induced DNA Damage and Oxidant/Antioxidant Status in Male Rats

Heikal¹

2012

J Environ Anal Toxicol

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Section: Discussionmentioning

confidence: 99%

Protective Effect of a Synthetic Antioxidant “Acetyl Gallate Derivative” Against Dimethoate Induced DNA Damage and Oxidant/Antioxidant Status in Male Rats

Heikal¹

2012

J Environ Anal Toxicol

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“…In these circumstances, liver enlargement was not associated with pathological changes, and the liver weights returned to control levels when the conditions causing the liver enlargement were terminated. Based on the results of studies of 11 drug candidate substances, Amacher et al (1998) concluded that liver weight increases of up to 50% with no more than slight elevations in levels of ALT or mild pathological changes should be interpreted as adaptive responses. Ennulat et al (2010) [citing Greaves (2007) and Schulte-Hermann et al (1974)] concluded that the most common histological change associated with liver enzyme induction was hepatocellular hypertrophy.…”

Section: Liver Enlargementmentioning

confidence: 99%

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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“…Microsomal enzyme inducers are known to cause hepatomegaly as an adaptive change without any evidence of liver injury in rats (Amacher et al, 1998 108.2 ± 1.9 108.2 ± 1.7 107.0 ± 1.3 106.8 ± 1.0 106.0 ± 1.7 104.8 ± 0.8 Ca, mg/dL 9.50 ± 0.33 9.68 ± 0.13 9.82 ± 0.16 10.13 ± 0.28** 9.83 ± 0.27 10.02 ± 0.44 IP, mg/dL 7.28 ± 0.70 7.33 ± 0.42 6.90 ± 0.62 7.52 ± 0.52 6.88 ± 0.58 7.13 ± 0.34 Values are expressed as the mean ± standard deviation. *Significantly different from the control group at P < .05 by the Dunnett multiple comparison test.…”

Section: Discussionmentioning

confidence: 99%

A 28-day repeated oral-dose toxicity study of insecticide synergist N-(2-ethylhexyl)-1-isopropyl-4-methylbicyclo[2.2.2] oct-5-ene-2,3-dicarboximide in rats

Matsumoto¹,

Furukawa

Kobayashi³

et al. 2018

Fundam. Toxicol. Sci.

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-N-(2-Ethylhexyl)-1-isopropyl-4-methylbicyclo[2.2.2]oct-5-ene-2,3-dicarboximide (Synepirin 500; CAS: 13358-11-7) is used as a synergist, a chemical that makes pesticide ingredients more effective. People can be exposed to Synepirin 500 by using insecticides containing this chemical or from residues in food. The Japanese government chose this chemical as a target substance in its existing chemical testing program. Crl:CD(SD) rats were administered 0, 40, 200, and 1000 mg/kg/day Synepirin 500 by gavage for 28 days, followed by a 14 day recovery period. Diarrhea or soft feces were observed in both sexes at 1000 mg/kg/day. Absolute and/or relative liver weights significantly increased at ≥ 40 mg/kg/day in females and at ≥ 200 mg/kg/day in males. Absolute and/or relative thyroid weights significantly increased in both sexes at 1000 mg/kg/day. These changes were still significant at the end of the recovery period in females. Significantly prolonged prothrombin time and activated partial thromboplastin time were observed in males receiving ≥ 40 mg/kg/day. Histopathological changes in the liver and thyroid were observed in both sexes at 1000 mg/kg/day. On the basis of the effects on the liver, the level of the lowest observed adverse effect from repeated doses of Synepirin 500 was judged to be 40 mg/kg/day for rats.

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The Relationship Among Microsomal Enzyme Induction, Liver Weight and Histological Change in Rat Toxicology Studies

Cited by 104 publications

References 20 publications

Protective Effect of a Synthetic Antioxidant “Acetyl Gallate Derivative” Against Dimethoate Induced DNA Damage and Oxidant/Antioxidant Status in Male Rats

Protective Effect of a Synthetic Antioxidant “Acetyl Gallate Derivative” Against Dimethoate Induced DNA Damage and Oxidant/Antioxidant Status in Male Rats

Characterization of the toxicological hazards of hydrocarbon solvents

A 28-day repeated oral-dose toxicity study of insecticide synergist N-(2-ethylhexyl)-1-isopropyl-4-methylbicyclo[2.2.2] oct-5-ene-2,3-dicarboximide in rats

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