Hepatotoxicity and carcinogenicity in female Sprague-Dawley rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): a pathology working group reevaluation.

Risk assessment for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been based in part on the incidences of liver neoplasms in female Sprague-Dawley (SD) rats reported in a 2-year study conducted by Dow Chemical Corporation and published in 1978. In the years subsequent to the Dow report, the criteria for the diagnosis of proliferative hepatocellular lesions in the rat have been refined based upon ongoing study of these lesions. Because of this, PATHCO, Inc., was requested to conduct an independent review of the liver slides from the Dow TCDD study in order to assess how the current terminology might impact on interpretation of proliferative liver lesions in rats compared to the terminology used in the past. In March 1990, a pathology working group (PWG) was convened to review proliferative lesions in the livers of the female rats. The results of the PWG's evaluation of the microslides indicated a trend in tumor incidence similar to that published in 1978 but with a lower incidence of tumors in the middle and high dose females. Based on the morphologic findings, including the fact that the tumors were predominantly benign and usually associated with lesions of hepatic toxicity, the PWG considered this study to demonstrate a weak oncogenic effect of TCDD in the livers of female SD rats. As a result of its review, the PWG noted that in order to establish a relationship between the toxic hepatitis and the hepatocellular neoplasms, an independent review and grading of the toxic lesions in all female rats would be required.(ABSTRACT TRUNCATED AT 250 WORDS)

Generally recognized as safe (GRAS) evaluation of 4-hexylresorcinol for use as a processing aid for prevention of melanosis in shrimp.

4-Hexylresorcinol (C12H18O2) is proposed for use as a processing aid for prevention of melanosis ("black spot") in shrimp and as an alternative to the currently approved sulfites. A safety evaluation was conducted to affirm, based upon scientific procedures, the generally recognized as safe ("GRAS") status of 4-hexylresorcinol for proposed use. The GRAS safety evaluation compiled, reviewed, and analyzed data on the following areas: chemical identity, analytical methodology, historical and proposed uses, functionality, and safety. The publicly available safety data on 4-hexylresorcinol cover a broad range of potential toxicity concerns including acute and subacute toxicity, subchronic toxicity, carcinogenicity, mutagenicity, and allergenicity. These studies, along with the aforementioned data, demonstrate that 4-hexylresorcinol presents no risk of toxicity at the levels proposed for treatment of shrimp, and the use of 4-hexylresorcinol as a processing aid to prevent melanosis in shrimp is GRAS.

Canine protothecosis: review of the literature and report of an additional case.

A review of protothecosis in dogs revealed that this malady usually begins in the gastrointestinal tract and progresses to systemic involvement. Clinical signs generally include bloody diarrhea or blood-stained feces as well as blindness, ataxia, and polyuria. Histologically, myriads of protothecal organisms in different stages of development are found in the granulomatous lesions. Two main species have been culturally identified: Prototheca zopfii and P wickerhamii. In the absence of cultural studies, species identification can be accomplished readily by immunofluorescence. The present case involved P zopfii infection in a 5-year-old female Cocker Spaniel that had bloody diarrhea, with a history of bloody diarrhea 6 months earlier.

Experimental lead paint poisoning in nonhuman primates. II. Clinical pathologic findings and behavioral effects.

Oral administration of lead-containing paint to rhesus monkeys induced anemia, more profound in older primates. Erythrocytes were microcytic and hypochromic, but tended to become macrocytic terminally. Stippled erythrocytes were increased in all poisoned monkeys, especially in those with high blood lead levels and anemia. Proteinuria, glycosuria, casts and sloughed tubular cells containing acid-fast inclusion bodies were found on urinalysis. Terminal elevations of blood urea nitrogen were associated with profound anemia and renal tubular damage. Repeated blood lead values over 200 microgram/dl were associated with a moribund termination while monkeys which had levels under 100 microgram/dl remained apparently healthy. Behavioral studies in a small number of subclinically poisoned juveniles and neonates failed to reveal deficiencies of visual acuity or cognitive ability, nor was there evidence of alterations in levels of activity.

Experimental lead paint poisoning in nonhuman primates. I. Clinical signs and course.

Lead-containing paints were administered orally to 27 rhesus monkeys for periods of 18-667 days. Lead acetate was fed to nine monkeys of three different species for 9-156 days. Excretion of one week's dose of lead in six primates ranged from 35 to 94%. The animals incurred moderate to extreme elevations of lead in blood, most lost weight, or had depressed weight gains, and developed Burtonian lines, some died suddenly and unexpectedly, and many terminated in a moribund state with profound anemia. Only one neonate had obvious signs of lead encephalopathy. The monkeys' ages, dose and source of lead, and possibly other factors, affected their response to lead.

Demyelinating encephalomyelopathy associated with lead poisoning in nonhuman primates.

Lead poisoning was diagnosed in four primates by the finding of toxic amounts of lead in tissues. Abnormalities in the brain and spinal cord were characterized by vascular lesions and demyelination. These findings suggest a new animal model for the study of demyelination and strengthen the supposition that lead may be a factor in some idiopathic demyelinating diseases.