Histopathology products

In vivo, patients treated with AZT develop a mitochondrial myopathy with mitochondrial DNA depletion, deficiency of cytochrome c oxidase (complex IV), intracellular fat accumulation, high lactate production and marked phosphocreatine depletion (Lewis and Dalakas 1995 Dalakas 2001). Clinically, the patient presents with fatigue, myalgia, muscle weakness, wasting and elevated serum creatine kinase. Muscle biopsy shows ragged red fibers , the characteristic histopathologic changes of mitochondrial myopathy, cansed by subsarcolemmal accumulation of mitochondria (Lewis and Dalakas 1995). 

No effect on milk production, feed intake, body weight, lymphocyte function, or histopathology of spleen, thymus, or lymph nodes. Postmortem examination showed enlarged liver, lungs, kidneys, and adrenals significant loss of renal function (Forsell etal. 1981 Kinzell etal. 1981)... 

Not only is it difficult to detect effects on male fertility because of group-size considerations, effects on male fertility mediated by decreased sperm production are also difficult to detect because of the normally huge excess of sperm included in a rat ejaculate. Sperm production can be decreased by up to 90% without effect on fertility (either pregnancy rate or litter size) in the rat. This is not the case for men, so the sperm excess in the rat represents a serious flaw in the rat model (see Working, 1988). To address this deficiency and improve the sensitivity of the model, it is advisable to determine the effects of the test agent on testes weights, testicular spermatid counts, and histopathology of the testes (preferably plastic sections) in the male fertility study and/or the 14-week toxicity study. In some cases, these parameters may be more predictive of possible effects on male fertility in humans than the fertility rate in rats. 

Dermal corrosion is the production of irreversible damage of the skin namely, visible necrosis through the epidermis and into the dermis, following the application of a test substance for up to four hours. Corrosive reactions are typified by ulcers, bleeding, bloody scabs, and, by the end of observation at 14 days, by discoloration due to blanching of the skin, complete areas of alopecia, and scars. Histopathology should be considered to evaluate questionable lesions. ... 

Adrenal histopathology May indicate alterations in steroid production (corticosteroids, sex steroid precursors)... 

Ovary histopathology Mating-, impairment of hormone production leading to lack of appropriate mating behavior and/or estrous cycle abnormalities Fertility reduced ovulation... 

Some end-points that detect endocrine-related effects in exposed adults are part of routine testing. These include some measures of fertility, reproductive organ appearance and weight, histopathology, oocyte number, cycle patterns and mating behaviour. Uterine protein production has also been used in toxicological assessment (Maier et al.,... 

Breslin et al. (1989) conducted a two-generation reproduction study in Fischer 344 rats with 1,3-dichloropropene (92% technical product). Male and female Fischer 344 rats were exposed by inhalation to 0, 10, 30 or 90 ppm [0, 45, 136 or 409 mg/m ] 1,3-dichloropropene for 6 h per day on five days per week for two generations. The parental F, and F, generations were each bred twice. Parental effects (decreased body weights, histopathological effects on nasal mucosa) occurred only at the highest concentration of 1,3-dichloropropene. No adverse effect on reproductive parameters or neonatal growth or survival was found in either of the Fj or , litters, even at the 90 ppm dose. 

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