Studies of the incidence of spontaneous pancreatic tumours in ageing CD rats.

A survey of the incidence of spontaneous pancreatic tumours in CD rats was carried out. The survey revealed islet cell adenomas to be the most common of pancreatic tumours with a higher incidence in untreated males (11.7% in comparison to in females 5.5%). 9040 untreated and 24578 treated rats were included in this survey. These rats were from two year carcinogenicity studies over a 15 year period. The sex difference appeared also in the incidence of islet cell carcinoma (males 2.4% vs females 1%). The third type of tumour was exocrine adenoma with an incidence of 2% in males, 0.1% in females. The last type, which was very rare in this strain, was exocrine carcinoma (0.08% in males, 0.02% in females). The tumour incidences were more in rats killed at termination than in those died or killed earlier during the study suggesting a late onset of these tumours. Exocrine carcinoma was rarest of all pancreatic tumours. In contrast to man, rat pancreatic tumours were not life-threatening in rats, except for exocrine carcinoma. Pancreatic tumours are somewhat age-related as they were very rare in young rats and appeared mainly in rats over 70 weeks of age. Cystic exocrine adenoma, cystic or duct exocrine adenocarcinoma reported in man, were not seen in rats. Exocrine tumours are fatal tumours in man with very poor prognosis. Pancreatic carcinomas in rats mostly showed only local invasion. On very rare occasions they showed metastasis in to liver, lung and bone marrow. Ductal/cystic exocrine carcinoma of man showed metastasis to liver, peripancreatic lymph nodes, lymphatics, skeletal muscle and the lung. Exocrine adenocarcinoma in man was twice as common in males as in females, comparable to the general incidence of pancreatic tumours in rats. Islet cell tumours in man show no clear difference between males and females which is in contrast to rats. Both in man and in rats pancreatic tumours appear to occur in the latter half of life span.

Survey of spontaneous dystrophic mineralisation of pineal gland in ageing rats.

The survey included 151 rats from several carcinogenicity studies up to 104 weeks and 260 rats from short-term studies up to 52 weeks. All studies were performed during the period 1990-1996. Young rats up to 52 weeks of age showed normal structural appearance, in 134 male rats the incidence of mineralisation was 6.3% and in 126 females the incidence was only slightly less at 5.6%. In ageing rats, 70-104 weeks, 88 males and 63 females showed far higher incidence of mineralisation, 83% and 57% respectively, showing that the incidence of mineralisation in ageing rats was higher in males than females. The focal mineralisation occurred mainly at the margin of the gland in the subcapsular region mostly adjacent to small blood vessels. On occasions these involved the parenchymal cells in the middle part of the gland. The focal mineralisation stained positive with von Kossa indicating presence of calcium and also with PAS (Pariodic Acid-Schiff method), indicating presence of neutral mucopolysaccharide. There was no evidence of positivity with Perl's stain (for ferric salts), Toluidine blue (for protein) or Alcian blue (for acid mucopolysaccharides). With Oil Red O there was evidence of presence of fat or lipid in pinealocytes.

Mast cell distribution in mice.

A survey on the distribution of mast cells in mice was carried out. Mast cells were present in abundance in tongue and to a lesser extent in sciatic nerve. Fewer numbers of mast cells were seen in lymph nodes, e.g. cervical, pararenal and iliac. Mast cells were not common in mesenteric lymph nodes in contrast to rats. Mast cells appeared to be widely distributed in different organs, e.g. salivary gland, cervix, vagina, uterus, epididymides, skeletal, muscle, ovaries, prostate, seminal vesicles, harderian glands, skin, adipose tissue, preputial gland, tail, urinary bladder, trachea, thymus and gall bladder. Mast cells were very few in heart, liver, bone marrow and lungs and generally fewer than in rats. Mast cells were very rare in spleen and adrenals. Scattered individual mast cells were occasionally seen in submucosa and serosa of stomach, oesophagus, small and large intestine. Mast cells were not seen in kidney, pituitary, testes, bone, spinal cord, brain, optic nerve and eyes. In lymph nodes mast cells appeared mainly in medullary sinusoids. There was no clear evidence of a difference between numbers of mast cells in animals of different age or sex. There was evidence of increased numbers of mast cells in inflammatory lesions and in cases of malignant tumours such as lymphomas. Presence of mast cells is incidental and is not indicative of any abnormalities.

Mast cell distribution in rats.

A survey on the distribution of mast cells in healthy rats was carried out. Mast cells were present in abundance in mesenteric lymph nodes and tongue and to a lesser extent in sciatic nerve. Fewer numbers of mast cells were seen in other lymph nodes, heart, salivary gland, thymus, pancreas, cervix, vagina, uterus, epididymis, liver, skeletal muscle, ovaries, prostate, seminal vesicles, harderian glands, parathyroid, thyroid, mammary gland, skin, adipose tissue, preputial gland, tail and bone marrow. Scattered individual mast cells were occasionally seen in submucosa and serosa of stomach, oesophagus, small and large intestine and urinary bladder. Mast cells were very rare in lung, spleen and adrenals. Mast cells were not seen in kidney, pituitary, testes, bone spinal cord, brain, optic nerves and eyes. In lymph nodes, mast cells appeared mainly in medullary sinusoids with varying extent. There was no clear evidence of a difference between numbers of mast cells in young and older animals. There was evidence of increased numbers of mast cells in inflammatory lesions, of skin and heart. Mast cells were seen associated with mammary tumours, fibromas and fibrosarcomas. There were more mast cells in rats than in mice. Mast cells appear to be more abundant in Wistar rats than in CD rats. Mast cells were hardly seen in healthy dogs and primates except a few in tongue and sciatic nerve. Presence of mast cells is incidental and not indicative of any abnormalities.

Survey on spontaneous systemic amyloidosis in aging mice.

The incidence of systemic amyloidosis in CD-1 mice (Charles River, caesarian derived) obtained from long term studies over more than a 15-year period is reported. The survey included samples of visceral organs, peripheral and central nervous tissues, bone and bone marrow. The total incidence in all mice of this survey did not show any clear evidence of a difference between males and females. Amyloidosis deposits were mainly seen in the stomach (glandular), heart, small intestines, kidney, liver, spleen, thyroid, parathyroid, adrenals, salivary glands and ovaries, but not in the brain, spinal cord, bone or bone marrow. The survey showed that amyloidosis in CD-1 mice was spontaneous, systemic and it is age-related. Amyloid deposition was extracellular and it stained positively with Congo Red and also stained positively with Oil Red O and Alcian blue. In general, amyloidosis in CD-1 mice, was higher in comparison with B6C3F (cross between C57BL/C6 NCRLB and C3H/HEN NCRLB, (bred by Charles River), CFLP strain (hysterectomy derived strain of Swiss origin) and MAGF: TIF (SPF). This survey also showed that spontaneous systemic amyloidosis in CD-1 mice, was one of the major factors contributory to death in aging CD-1 mice.

Survey on spontaneous peripheral neuropathy in aging mice.

The incidence of peripheral neuropathy in CD-1 mice (caesarean-derived) obtained from long term studies over a 10 year period is reported. The survey included peripheral nerve samples of 15,223 males and 15,075 females. The incidence of peripheral neuropathy is 8% in untreated males and 12% in untreated females aged 80 to 104 weeks. The total incidence in all mice in the survey was higher in females than males and was age-related. The present survey also showed interstrain differences. The peripheral neuropathy in CD-1 strain was low in incidence compared to B6C3F1 (cross between C57 BL/C6NCLB and C3H/HENCRLB). The peripheral neuropathy was spontaneous in origin and was age-related.

Survey on spontaneous peripheral neuropathy in aging rats.

The incidence of peripheral neuropathy in rats (Charles River bred, caesarean derived, Sprague-Dawley origin) obtained from long term studies over a 10 year period is reported. The survey included peripheral nerve samples from 14,237 males and 13,668 females. The incidence of peripheral neuropathy is 23% in untreated males and 18% in untreated females at 80-104 weeks of age. The total incidence in all rats in the survey was somewhat higher in males than females. The light and electron microscopic features of age-related peripheral neuropathy in rats is described. The peripheral neuropathy was spontaneous in origin and was age-related.

Dystrophic mineralisation in cerebrum of aging mice.

The incidence of cerebral dystrophic mineralisation in CD-1 mice (Charles River bred, cesarean-derived) obtained from long term studies over a 10 year period is reported. The survey included brain samples from 15869 males and 15729 females. The incidence of cerebral dystrophic mineralisation is 0.6% in untreated males and 0.3% in untreated females. The total incidence in all mice in the survey showed higher incidence in males than females and was age-related. The present survey also showed interstrain differences. The mineralisation in CD-1 strain was low in incidence and B6C3Fl (cross between C57BL/C6 NCR LB and C3H/HEN NCR LB, bred by Charles River) with relatively high incidence. The foci of mineralisation was dystrophic and probably of neuronal origin in this survey.

Mast cell tumours in CD-1 mice.

A survey of the occurrence of mast cell tumours in CD-1 mice (Caesarian derived) recorded nine tumours in 24352 mice used for carcinogenicity studies over a period of six years (1984-1989). All except one appeared as multi centric tumours. Three of the mice had deposits only in the bone marrow, one of those cases was associated with intestinal adenocarcinoma and harderian gland adenoma. Case four had deposits in lung, thymus, lymph nodes, liver, spleen and kidney and occurred in association with pulmonary adenocarcinoma and pleomorphic lymphoma. Case five showed the tumour deposits in mesenteric lymph nodes and liver. Case six showed deposits of the tumour in lung, liver, kidney and bone marrow and in this case there was also a cutaneous fibrosarcoma. Case seven was diagnosed as mast cell leukaemia. Case eight was a subcutaneous tumour, case nine showed subcutaneous deposits and deposits in lungs, lymph nodes, liver, spleen and bone marrow.

Harderian gland tumours in mice.

A survey of the occurrence of harderian gland tumours in Charles River CD-1 mice (Caesarian derived) showed a relatively higher incidence of harderian gland adenomas in males (5%) in comparison with females (2%) among 3302 untreated control mice from two-year carcinogenicity studies. This sex difference did not apply to the incidence of harderian gland carcinomas. Porphyrin pigment was observed in some of the tumours. Metastasis of the harderian gland carcinoma was seen in lymph node and lung, and in one case the thymus and liver was also affected. Vacuolation, due to fat was seen as helpful diagnostic feature.

Occurrence of the lungworms Capillaria and Crenosoma spp. in British hedgehogs (Erinaceus europaeus).

Fifty-three dead hedgehogs (Erinaceus europaeus) were investigated histologically for evidence of lungworm infestation. The faeces of forty-two were examined microscopically for nematode eggs. Thirty-five animals showed parasitic lesions--fourteen Crenosoma only, five Capillaria only and sixteen both. Infestations were characterized by inflammatory changes in the trachea and lung and the presence of worms in other organs. There was some correlation between the finding of parasites in histological sections and the detection of eggs in faeces but, neither method appears completely reliable.

Giant-cell tumour of soft tissue in two Sprague-Dawley rats.

Two cases of soft tissue giant-cell tumours are reported in Sprague-Dawley rats. The lesions had the characteristic appearance of multinucleate tumour giant cells and were unassociated with bone. A search of the literature failed to reveal any previous report of this lesion in the rat.

A report on drug-induced kerato-conjunctivitis sicca in dogs.

Kerato-conjunctivitis sicca is reported in beagle dogs treated with an antispasmodic compound for 26 weeks during a routine toxicity study. There was a deficiency of lachrymal secretion associated with keratitis and corneal vascularization. Histopathologically, the changes were characterized by vascularization, fibroblast proliferation and infiltration of inflammatory cells in the substantia propria. In some cases, the inflammation also occurred in corneal epithelium, ocular conjunctiva and corneal limbi.

The toxicity of gossypol to the male rat.

When (+/-) gossypol acetic acid was administered to male Sprague-Dawley rats for 26 weeks, the most significant toxicological finding was marked suppression of body weight gain in rats receiving 25 mg/kg per day. Minor biochemical changes were noted at this dosage level. Terminal studies showed 6 out of 20 rats receiving 25 mg/kg per day to have varying degrees of testicular pathology. Five mg/kg per day was shown to be a "no effect" level.

Malignant phaeochromocytoma with widespread metastasis in the rat.

Malignant phaeochromocytomas occurring in the adrenals of 2 aged male rats are reported. The primary tumour was unilateral and had metastasized to the other adrenal, pancreas, liver, spleen, lung, kidney and bone marrow. Metastatic deposits were also seen in a co-existing pituitary tumour and in an islet cell carcinoma of the pancreas. The cells, although resembling normal medullary cells, were smaller and had sparse cytoplasm; the nuclei were generally hyperchromatic. The cells were arranged in nests and sometimes in a trabecular pattern. The presence of phaeochromocytomas with widespread metastasis is of interest since, in general, phaeochromocytomas of rats are not prone to metastasize. In addition, invasion into a pancreatic islet cell tumour and into a pituitary tumour was unusual.

Pox-like lesions in a colony of carp (Cyprinus carpio).

Twelve carp (Cyprinus carpio) out of a total of 100 were affected with skin nodules, mainly located on the dorsal and lateral surface. Post mortem examination of six of the worst affected fish showed the nodules consisting of white gel-like outgrowths. No abnormality was apparent in any other tissue examined. Microscopically, the nodules were formed by proliferating hyperplastic epidermal cells. The other six fish were left for recovery and their nodules regressed spontaneously. The possible aetiological factors are listed.

Tumorigenic and toxic effect of O,S-dibenzoyl thiamine hydrochloride in prolonged dietary administration to rats.

The chronic toxicity of O,S-dibenzoyl thiamine hydrochloride (DBT) was studied by prolonged dietary administration to rats at dosages of 1000 and 10 000 ppm. The study confirmed the low toxicity of this compound and absence of carcinogenicity.

Mineralisation in kidney and stomach of beagle dogs.

Histological examination of 753 Beagle dogs showed renal foci of calcification in 27.9% of males and 21.5% of females. In contrast, stomach calcification was observed in 6.2% of males and 5.2% of females examined. It is suggested that the focal calcification seen in both organs was possibly of dietary origin and may have been related to the phosphate content.