lib.mainmenu_1

 
 

Toxicity

Essentially all of the information pertaining to health effects of PCDFs in humans is from the Yusho and Yu-Cheng rice oil poisoning incidents. No definite information is available on human health effects of acute oral exposure to PCDFs because exposure during these incidents predominately involved intermediate-duration exposure. Information on humans exposed to PCB fires, particularly PCB mixtures not containing chlorinated benzenes (which can form PCDDs), could possibly help characterize health effects of PCDFs following acute dermal and/or inhalation exposure. Health effects associated with the Binghamton State Office Building electrical transformer fire cannot be attributed solely to PCDFs or any of the other components of the soot due to the mixture of chemicals, which included chlorinated benzenes and PCDDs, and other confounding factors.

Relatively little information is available on systemic effects of acute duration oral exposure to PCDFs in animals. Several effects have been observed, including histopathologic and possible functional changes in the kidneys and gastrointestinal tract and evidence of wasting and anaemia. Many of these effects occurred at lethal or other high doses, although effects in the guinea pig, which is the most sensitive species tested in acute oral studies, are relatively well characterized. Since acute toxicity of furans may depend more on total dose, rather than frequency of dosing, and is characteristically delayed in expression, some information from intermediate duration oral studies is relevant to acute exposure. Data on effects in animals following acute dermal or inhalation exposure to PCDFs are not available, although mobilization of PCDFs from adipose tissue to target organs is likely to be similar, regardless of the route of exposure.

Acute dermal studies are relevant because skin is a route of concern for exposure at or near hazardous waste sites, particularly due to possibilities for brief contact. Acute inhalation studies are unlikely to be relevant, due to the low potential for inhalation exposure in the vicinity of hazardous waste sites and ambient air.

U.S. National Toxicity Program acute toxicity studies for 2,3,7,8-TCDD

Study typeRouteSpeciesResultUnits
LD50DermalRabbit275.0ug/m3
LD50IntraperitonealHamster3.0mg/m3
LD50IntraperitonealMouse120.0ug/m3
LD50IntraperitonealRabbit252.0ug/m3
LD50IntraperitonealRat60.0ug/m3
LD50OralGuinea pig500.0ng/m3
LD50OralHamster1157ug/m3
LD50OralMonkey2.0ug/m3
LD50OralMouse114.0ug/m3
LD50OralRat20.0ug/m3

Most of the existing toxicity information for CDFs is available from intermediate duration studies of orally-exposed humans following Yusho and Yu-Cheng poisoning and animals. Dermal and ocular effects; mild anaemia; mild and transient hepatic alterations, including increased serum levels of triglycerides and liver enzymes and related ultrastructural changes; and bronchitis and other respiratory effects secondary to infection, were most consistently observed in the exposed humans. Although some estimates of doses associated with some effects of Yusho and Yu-Cheng exposure are available, these probably do not reflect the most sensitive toxic end points, as indicated by studies in rats, guinea pigs, and monkeys. Some systemic effects of intermediate duration oral PCDFs exposure in animals are consistent with the effects observed in humans, but the animal studies better characterize progression of certain effects (e.g., liver toxicity) and have identified other systemic effects (e.g., wasting syndrome, stomach mucosal lesions). Hepatic effects in rats were used as a basis for an intermediate-duration oral MRL. Because of limitations in the database, it is unclear whether different species should be used for studying effects on different target organs.

The only information available on systemic toxicity of intermediate duration dermal exposure is from a study in mice, which found effects in the stomach and liver and on body weight, however, these data are suggestive of similar effects by both dermal and oral routes.

No data were located regarding effects in animals after intermediate-duration inhalation exposure, but inhalation is a minor route of concern for humans.

No information is available on effects in humans or animals following chronic exposure to PCDFs by any route.

 


Structure formula of 2,3,7,8-Tetrachlorodibenzo-furan