Toxicity and disposition of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF) in the rhesus monkey (Macaca mulatta).
The toxicity and disposition of 2,3,4,7,8-pentachlorodibenzofuran (4PeCDF), a ubiquitous and acutely toxic environmental contaminant, was examined in three adult male Rhesus monkeys administered a single iv dose of 34 micrograms (0.1 mumol)/kg. Within 20 min, 4PeCDF was eliminated from the blood and was distributed to the liver, skin, adipose, and muscle tissues. Excretion occurred primarily via the feces with a minimum whole body half-life approximately 38 days. Within 7-14 days after administration, the packed cell volume and serum triglyceride and bile acid concentrations were significantly increased while serum cholesterol, protein, and albumin concentrations were decreased relative to pretreatment levels. Thyroid hormone levels were also altered with an increase in TSH and a decrease in T3 and T4 concentrations. After 28 days, two monkeys began exhibiting alopecia, hyperkeratinization of the toe and finger nails, facial chloracne-like lesions, and loss of body weight. They subsequently died 40 and 48 days after treatment. Similar symptoms of toxicity were observed in the third animal 58 days after 4PeCDF administration, but this animal appeared to fully recover and was administered 4PeCDF orally and [3H]1,2,3,7,8-pentachloro-dibenzofuran (1PeCDF) dermally 238 days after the initial iv dose. In this animal, approximately 2% of an oral dose of [14C]-4PeCDF was absorbed from the stomach and small intestine in 6 hr and was distributed mainly to the muscle and skin and less than 99% of a dermal dose of 1PeCDF remained at the site of application. Pathological findings in the monkeys that died indicated hyperplastic and metaplastic changes in the gastric mucosa, the Meibomian glands of the eyelid, and the ceruminous glands of the ear. Regression of these lesions was present in the surviving animal. Therefore, 4PeCDF produces dioxin-like toxicity in the monkey similar to that reported for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and in the same dose range.
Brewster
D W
DW
Systemic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27707.
Elwell
M R
MR
Birnbaum
L S
LS
D000042:Absorption; D000818:Animals; D001572:Benzofurans / Q000493:pharmacokinetics* / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D002250:Carbon Radioisotopes; D004785:Environmental Pollutants / Q000493:pharmacokinetics* / Q000633:toxicity; D005753:Gastric Mucosa / Q000473:pathology; D006207:Half-Life; D008253:Macaca mulatta; D008297:Male; D009132:Muscles / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D013963:Thyroid Hormones / Q000097:blood; D014018:Tissue Distribution
D001572:Benzofurans; D002250:Carbon Radioisotopes; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D013963:Thyroid Hormones; C038890:2,3,4,7,8-pentachlorodibenzofuran