BIOMAT Database Logo BIOMAT Database Logo

Examination of low-incidence brain tumor responses in F344 rats following chemical exposures in National Toxicology Program carcinogenicity studies. 1999

R C Sills, and J R Hailey, and J Neal, and G A Boorman, and J K Haseman, and R L Melnick
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. sills@niehs.nih.gov

Neoplasms in the brain are uncommon in control Fischer 344 (F344) rats; they occur at a rate of less than 1% in 2-yr toxicity/carcinogenicity studies. Furthermore, only 10 of nearly 500 studies conducted by the National Toxicology Program (NTP) showed any evidence of chemically related neoplastic effects in the brain. Generally, the brain tumor responses were considered equivocal, because the characteristics of potential neurocarcinogenic agents (such as statistically significant increased incidences, decreased latency and/or survival, and demonstration of dose-response relationships) were not observed. A thorough examination, including comparisons with a well-established historical database, is often critical in evaluating rare brain tumors. Chemicals that gave equivocal evidence of brain tumor responses were generally associated with carcinogenicity at other sites, and many chemicals were mutagenic when incubated with metabolic activating enzymes. Other factors that were supportive of the theory that marginal increases in brain tumor incidence were related to chemical exposure were that (a) some of the tumors were malignant, (b) no brain neoplasms were observed in concurrent controls from some studies, and/or (c) brain tumors were also seen following exposure to structurally related chemicals. In 2-yr studies in F344 rats (studies conducted by the NTP), equivocal evidence of carcinogenicity was observed for the following 9 chemicals: isoprene, bromoethane, chloroethane, 3,3'-dimethylbenzidine dihydrochloride, 3,3'-dimethoxybenzidine dihydrochloride, furosemide, C.I. direct blue 15, diphenhydramine hydrochloride, and 1-H-benzotriazole. Glycidol was the only chemical evaluated by the NTP with which there was clear evidence of brain tumor induction in F344 rats. Clarification of the potential neurocarcinogenic risks of chemicals that produce equivocal evidence of a brain tumor response in conventional 2-yr rodent studies may be aided by the use of transgenic mouse models that exhibit genetic alterations that reflect those present in human brain tumors as well as by the use of in utero exposures.

UI MeSH Term Description Entries
D008297 Male Males
D008579 Meningioma A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7) Benign Meningioma,Malignant Meningioma,Meningiomas, Multiple,Meningiomatosis,Angioblastic Meningioma,Angiomatous Meningioma,Cerebral Convexity Meningioma,Clear Cell Meningioma,Fibrous Meningioma,Hemangioblastic Meningioma,Hemangiopericytic Meningioma,Intracranial Meningioma,Intraorbital Meningioma,Intraventricular Meningioma,Meningotheliomatous Meningioma,Microcystic Meningioma,Olfactory Groove Meningioma,Papillary Meningioma,Parasagittal Meningioma,Posterior Fossa Meningioma,Psammomatous Meningioma,Secretory Meningioma,Sphenoid Wing Meningioma,Spinal Meningioma,Transitional Meningioma,Xanthomatous Meningioma,Angioblastic Meningiomas,Angiomatous Meningiomas,Benign Meningiomas,Cerebral Convexity Meningiomas,Clear Cell Meningiomas,Convexity Meningioma, Cerebral,Convexity Meningiomas, Cerebral,Fibrous Meningiomas,Groove Meningiomas, Olfactory,Hemangioblastic Meningiomas,Hemangiopericytic Meningiomas,Intracranial Meningiomas,Intraorbital Meningiomas,Intraventricular Meningiomas,Malignant Meningiomas,Meningioma, Angioblastic,Meningioma, Angiomatous,Meningioma, Benign,Meningioma, Cerebral Convexity,Meningioma, Clear Cell,Meningioma, Fibrous,Meningioma, Hemangioblastic,Meningioma, Hemangiopericytic,Meningioma, Intracranial,Meningioma, Intraorbital,Meningioma, Intraventricular,Meningioma, Malignant,Meningioma, Meningotheliomatous,Meningioma, Microcystic,Meningioma, Multiple,Meningioma, Olfactory Groove,Meningioma, Papillary,Meningioma, Parasagittal,Meningioma, Posterior Fossa,Meningioma, Psammomatous,Meningioma, Secretory,Meningioma, Sphenoid Wing,Meningioma, Spinal,Meningioma, Transitional,Meningioma, Xanthomatous,Meningiomas,Meningiomas, Angioblastic,Meningiomas, Angiomatous,Meningiomas, Benign,Meningiomas, Cerebral Convexity,Meningiomas, Clear Cell,Meningiomas, Fibrous,Meningiomas, Hemangioblastic,Meningiomas, Hemangiopericytic,Meningiomas, Intracranial,Meningiomas, Intraorbital,Meningiomas, Intraventricular,Meningiomas, Malignant,Meningiomas, Meningotheliomatous,Meningiomas, Microcystic,Meningiomas, Olfactory Groove,Meningiomas, Papillary,Meningiomas, Parasagittal,Meningiomas, Posterior Fossa,Meningiomas, Psammomatous,Meningiomas, Secretory,Meningiomas, Sphenoid Wing,Meningiomas, Spinal,Meningiomas, Transitional,Meningiomas, Xanthomatous,Meningiomatoses,Meningotheliomatous Meningiomas,Microcystic Meningiomas,Multiple Meningioma,Multiple Meningiomas,Olfactory Groove Meningiomas,Papillary Meningiomas,Parasagittal Meningiomas,Posterior Fossa Meningiomas,Psammomatous Meningiomas,Secretory Meningiomas,Sphenoid Wing Meningiomas,Spinal Meningiomas,Transitional Meningiomas,Wing Meningioma, Sphenoid,Wing Meningiomas, Sphenoid,Xanthomatous Meningiomas
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D010420 Pentanes Five-carbon saturated hydrocarbon group of the methane series. Include isomers and derivatives. Isopentanes
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D001932 Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D002070 Butadienes Four carbon unsaturated hydrocarbons containing two double bonds. Butadiene Derivative,Butadiene Derivatives,Derivative, Butadiene,Derivatives, Butadiene
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D004155 Diphenhydramine A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. Benhydramin,Diphenylhydramin,2-Diphenylmethoxy-N,N-dimethylethylamine,Allerdryl,Benadryl,Benylin,Benzhydramine,Dimedrol,Diphenhydramine Citrate,Diphenhydramine Citrate (1:1),Diphenhydramine Hydrochloride,Diphenylhydramine,Dormin,Citrate, Diphenhydramine,Hydrochloride, Diphenhydramine
D004852 Epoxy Compounds Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS. Epoxide,Epoxides,Epoxy Compound,Oxiranes,Compound, Epoxy,Compounds, Epoxy

Related Publications

R C Sills, and J R Hailey, and J Neal, and G A Boorman, and J K Haseman, and R L Melnick
Comparison of site-specific and overall tumor incidence analyses for 81 recent National Toxicology Program carcinogenicity studies.
June 1986, Regulatory toxicology and pharmacology : RTP,
R C Sills, and J R Hailey, and J Neal, and G A Boorman, and J K Haseman, and R L Melnick
Chemical Exacerbation of Light-induced Retinal Degeneration in F344/N Rats in National Toxicology Program Rodent Bioassays.
August 2016, Toxicologic pathology,
R C Sills, and J R Hailey, and J Neal, and G A Boorman, and J K Haseman, and R L Melnick
Observations on altered hepatocellular foci in National Toxicology Program two-year carcinogenicity studies in rats.
January 1989, Toxicologic pathology,
R C Sills, and J R Hailey, and J Neal, and G A Boorman, and J K Haseman, and R L Melnick
Toxicology and carcinogenicity studies of diuretics in F344 rats and B6C3F1 mice. 2. Furosemide.
October 1990, Journal of applied toxicology : JAT,
R C Sills, and J R Hailey, and J Neal, and G A Boorman, and J K Haseman, and R L Melnick
Toxicology and carcinogenicity studies of diuretics in F344 rats and B6C3F1 mice. 1. Hydrochlorothiazide.
October 1990, Journal of applied toxicology : JAT,
R C Sills, and J R Hailey, and J Neal, and G A Boorman, and J K Haseman, and R L Melnick
Ovarian toxicity and carcinogenicity in eight recent National Toxicology Program studies.
August 1987, Environmental health perspectives,
R C Sills, and J R Hailey, and J Neal, and G A Boorman, and J K Haseman, and R L Melnick
New diet (NTP-2000) for rats in the National Toxicology Program toxicity and carcinogenicity studies.
July 1996, Fundamental and applied toxicology : official journal of the Society of Toxicology,
R C Sills, and J R Hailey, and J Neal, and G A Boorman, and J K Haseman, and R L Melnick
Inhalation toxicology of isoprene in F344 rats and B6C3F1 mice following two-week exposures.
June 1990, Environmental health perspectives,
R C Sills, and J R Hailey, and J Neal, and G A Boorman, and J K Haseman, and R L Melnick
Immunohistochemical investigation of F344/N rat islet cell tumors from national toxicology program studies.
July 2012, Toxicologic pathology,
R C Sills, and J R Hailey, and J Neal, and G A Boorman, and J K Haseman, and R L Melnick
Results from 86 two-year carcinogenicity studies conducted by the National Toxicology Program.
January 1984, Journal of toxicology and environmental health,
Copied contents to your clipboard!