Toxicological consequences of Aroclor 1254 ingestion by female rhesus (Macaca mulatta) monkeys and their nursing infants. Part 3: post-reproduction and pathological findings.

A group of 80 menstruating rhesus (Macaca mulatta) monkeys were randomly allocated to four similar rooms (20 monkeys/room) and then to one of five dose groups (four females/dose group/room). Each day the monkeys self-ingested capsules containing doses of 0, 5, 20, 40 or 80 microg Aroclor 1254/kg body weight. After 25 months of continuous dosing, approximately 90% of the treated females had attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl (PCB) in their nuchal fat pad. Concurrently, sebaceous glands were being examined for changes analogous to chloracne. Subsequently, the females were paired with untreated males. The infants' blood PCB levels at birth were not correlated with its dam's dose or blood PCB level. However, there was an association between an infants preweaning blood PCB levels and its dam's dose and PCB milk levels. After weaning, the infants were not dosed with PCB. The half-life for the PCB in the infants' blood was determined and found to be slightly more than 15 wk. After 6 yr on test, three monkeys from the 0, 5, 20 and 40 microg dose groups were randomly allocated to a depletion study to ascertain the half-lives of specific PCB congeners (Mes et al., Chemosphere 1995, 30, 789-800). Concurrently, necropsies began of the remaining females, and of seven infants from the treated dams and four infants from the control dams, which had attained an age of 2 yr. Approximately 3 yr later, the depletion monkeys were necropsied. The only statistically significant treatment-related pathological changes found during the study were in the adult females, in which an involution of the sebaceous glands and a dose related increase in liver weight due to hyperplasia were evident.

Prevalence of endometriosis in rhesus (Macaca mulatta) monkeys ingesting PCB (Aroclor 1254): review and evaluation.

A total of 80 menstruating rhesus monkeys (Macaca mulatta) were equally and randomly divided among groups receiving 0, 5, 20, 40, or 80 mu g of Aroclor 1254/kg body weight/day during a 6-year toxicological-reproduction study. During the first 3 years of the study, 4 of the treated monkeys became moribund and were euthanized; 3 had endometriosis. This finding suggested a possible link between the PCB treatment and the occurrence of endometriosis. However, neither a laparoscopic examination of the control and high-dose monkeys nor the necropsy data provided evidence for a possible link between the PCB treatment and the observed incidence (37% (6/16) of controls; 25% (16/64) of treated monkeys and/or the severity of the endometrial lesions. Additional clinical and historical data not contained in previous reports are presented to facilitate independent evaluation of the relationship between PCB ingestion and endometriosis. We conclude that the incidence and severity of the endometriosis lesions observed in the rhesus monkeys utilized in this study did not have any relationship with the dosages of Aroclor 1254 they ingested.

Angiofollicular lymphoid hyperplasia in an angiolipomatous mass.

A posterior mediastinal mass was composed of angiolipomatous and lymphoid tissue. The lymphoid tissue took the form of multiple nodules with appearances similar to those of angiofollicular lymphoid hyperplasia. The findings support the view that this form of lymphoid hyperplasia may be of hamartomatous nature.

Renal oncocytoma. Study of eight cases.

Eight renal oncocytomas are described. Clinical manifestations were present in 3 cases, with hematuria occurring in 2 and flank pain in 2. Tumors were between 2.5 and 10.0 cm. in diameter and showed considerable variation in histologic pattern. The tan coloration of some tumors may permit a naked-eye distinction from renal cell carcinoma. All tumors appeared to be benign.

Ultrastructural studies on testicular biopsies from eighteen cases of hypospermatogenesis.

An electron microscopic study was conducted on biopsies from 18 young hypospermatogenic patients. No signs of "tubular blockage" or "germinal disorganization" were found. The relationships between the different components of the germinal epithelium were comparable to those found in normal testes. Germ cells were often connected by cytoplasmic bridges and Sertoli cells by typical narrow junctions, which, in the case of very depleted tubules, were very extensive and of irregular outline owing to the interdigitations of the cells. Sertoli cells had normal cytologic characteristics and, contrary to the findings of other investigators in similar material, had apparently a normal amount of lipid droplets and microfilaments. In six cases, a large number of thick, banded collagen fibers substituted for the microfibrils usually found between the myoid cells in the tunica propia. The possible significance of these changes as a cause or as a consequence of the tubular changes is not yet clear.

Crohn's disease of the appendix.

Granulomatous inflammation typifying Crohn's disease was centred within or confined to appendices in six patients, two of whom developed lesions attributable to Crohn's disease elsewhere in the gut. The remaining four patients have remained symptom-free for periods varying from two to six years. Histological evidence of Crohn's disease was also present in five of 46 appendices available for re-examination in a survey of 63 cases of Crohn's enterocolitis. It is adduced that appendiceal involvement in Crohn's disease is not uncommon.