The literature on 506 selected chemicals has been evaluated for evidence that these chemicals induce tumors in experimental animals and this assessment comprises the Gene-Tox Carcinogen Data Base. Three major sources of information were used to create this evaluated data base: all 185 chemicals determined by the International Agency for Research on Cancer to have Sufficient evidence of carcinogenic activity in experimental animals, 28 selected chemicals bioassayed for carcinogenic activity by the National Toxicology Program/National Cancer Institute and found to induce tumors in mice and rats, and 293 selected chemicals which had been evaluated in genetic toxicology and related bioassays as determined from previous Gene-Tox reports. The literature data on the 239 chemicals were analyzed by the Gene-Tox Carcinogenesis Panel in an organized, rational and consistent manner. Criteria were established to assess individual studies employing single chemicals and 4 categories of response were developed: Positive, Negative, Inconclusive (Equivocal) and Inconclusive. After evaluating each of the individual studies on the 293 chemicals, the Panel placed each of the 506 chemicals in an overall classification category based on the strength of the evidence indicating the presence or absence of carcinogenic effects. An 8-category decision scheme was established using a modified version of the International Agency for Research on Cancer approach. This scheme included two categories of Positive (Sufficient and Limited), two categories of Negative (Sufficient and Limited), a category of Equivocal (the evidence of carcinogenicity from well-conducted and well-reported lifetime studies had uncertain significance and was neither clearly positive nor negative), and three categories of Inadequate (the evidence of carcinogenicity was insufficient to make a decision, however, the data suggested a positive or negative indication). Of the 506 chemicals in the Gene-Tox Carcinogen Data Base, 252 were evaluated as Sufficient Positive, 99 as Limited Positive, 40 as Sufficient Negative, 21 as Limited Negative, 1 as Equivocal, 13 as Inadequate with the data suggesting a positive indication, 32 as Inadequate with the data suggesting a negative indication, and 48 Inadequate with the data not suggesting any indication of activity. This data base was analyzed and examined according to chemical class, using a 29 chemical class scheme.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMedDate not supplied

An analysis of the Gene-Tox Carcinogen Data Base.

The Gene-Tox Carcinogen Data Base is an evaluated source of cancer data on 506 chemicals selected in part for their previous assessment in genetic toxicology bioassays. This data base has been analyzed for the distribution of these chemicals into chemical classes. The major chemical classes (6% or greater of the total data base) are: acyl-, alkyl-, and aryl-halides; alcohols and phenols; aliphatic and aromatic amines, amides, and sulfonamides; benzene-ring-containing chemicals; organo-lead, -mercury, -phosphorous compounds, metals and derivatives, phosphoric acid esters, and phosphoramides; and polycyclic aromatic hydrocarbons. Cancer studies representing a subset of the Gene-Tox Carcinogen Data Base, 199 chemicals which were rated as Sufficient Positive/Negative or Limited Positive/Negative, were examined for distribution of those studies by animal species, gender, route of chemical administration, duration of study, major tumor sites, and major tumor types. These analyses revealed that the Gene-Tox Carcinogen Data Base contains a large number of lifetime studies involving the rat and mouse treated by oral routes of administration. The major organs that were targets were: liver, lung, skin, forestomach, bladder, and mammary gland, while the major tumor types were: carcinoma, sarcoma, papilloma, and adenoma. Chemicals in the data base have been assessed for species-specific carcinogenic effects, and these results indicate that for mice and rats there is a high correspondence (85%). This number is higher than that (71%) reported by Tennant et al. (1986) based on the recent results of 72 chronic cancer bioassays performed by the National Toxicology Program. This difference is probably based on the nature of the chemicals selected for inclusion in both data bases. Although the absolute value of this correspondence is unknown, it would seem to be within this range. When chemicals in the Gene-Tox Carcinogen Data Base were examined for their previous evaluation in 73 genetic toxicology bioassays, only 26 of these bioassays had 30 or more chemicals. In these 26 bioassays, the prevalence of positive chemicals was generally greater than 80-90%. This suggests that a thorough evaluation of genetic toxicology bioassays in regard to their ability to predict carcinogenic effects in animals is premature at this time.

Animals↗

PubMedDate not supplied

Neuroretinal function is normal in early dementia of the Alzheimer type.

We recently demonstrated that retinal ganglion cell function, optic nerve head parameters and the retinal nerve fiber layer thickness are not altered in early dementia of the Alzheimer type (DAT). Our current objective was to assess whether the function of cells located more distally in the retina is also unaffected by the disease. We evaluated 23 individuals with early to moderate DAT and 23 healthy age-matched subjects, all displaying clinically normal visual function. Scotopic and photopic flash electroretinograms (fERGs) and oscillatory potentials (OPs) were recorded. The amplitude and latency of the retinal potentials did not differ between DAT and control subjects. Our current results showing normal fERGs and OPs in early DAT indicate that the underlying neurons giving rise to these signals are not impaired by the disease process. These data support and extend our recent findings suggesting that visual deficits in DAT do not stem from neuroretinal dysfunction.

Aged↗

PubMedDate not supplied

Sensory-motor and cognitive functioning in children who have undergone bone marrow transplantation.

Sensory-motor and cognitive functioning was investigated in a group of 32 children treated with bone marrow transplantation (BMT), 1-6 years after treatment. Twenty-five of the patients had suffered from leukemia. The BMT procedure had involved a regimen of cytostatic drugs and, for leukemia patients, total body irradiation at a dose of 10 Gy, administered in one session. Cytostatic drugs and irradiation are known to be potentially neurotoxic, particularly when combined. The examination involved four neuropsychological tests of sensory-motor and cognitive functioning, as well as an age-appropriate intelligence test. For control the bone marrow donors (n = 32), siblings of the patients, were also investigated. A pronounced delay in motor development was found in four children, who had been treated with BMT including total body irradiation before 3 years of age. Patients between 3 and 11 years of age at BMT were at a slight disadvantage, compared to donors, on tasks involving perceptual and fine motor speed. In older patients no deficits were observed.

Adolescent↗