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Toxicity

Acute exposure of humans to 2,3,7,8TCDD can cause chloracne and hepatic effects. Specifying the route of exposure in these human cases is difficult because the individuals were probably exposed by a combination of routes. Furthermore, human data did not provide any information regarding exposure levels and coexposure to other chemicals confounds the results. Also, in most cases, the exposed subjects were examined long after exposure occurred. Acute oral exposure to 2,3,7,8TCDD caused delayed type of death in all animal species tested, and LD50 values have been determined for rats,  rabbits, guinea pigs, and hamsters, see (table below). Furthermore, an acute LD50 was calculated for rats and mice exposed to a mixture of 1,2,3,6,7,8HxCDD and 1,2,3,7,8,9HxCDD. No deaths were observed with other congeners (2,7DCDD, 1,2,3,4,6,7,8HpCDD, 1,2,3,4,6,7,8,9OCDD) tested, and 2,3,7,8TCDD proved to be the most toxic dioxin. However, interspecies and interstrain differences were found in the susceptibility to PCDDs. Systemic effects observed in animals after acute oral exposure to 2,3,7,8TCDD included cardiovascular, gastrointestinal, hematological, hepatic, renal, endocrine, dermal effects, and body weight loss. Hepatic and body weight effects were the main signs of 2,3,7,8TCDD toxicity and occurred also after exposure to a mixture of 1,2,3,6,7,8HxCDD and 1,2,3,7,8,9HxCDD. Immunological effects were observed following low oral doses of 2,3,7,8TCDD, and an acute oral MRL was based on a NOAEL for immunological effects.
Limited data were located regarding effects in animals after acute inhalation exposure to PCDDs.
No information was located regarding health effects of other congeners in humans, and limited data exist about effects caused by an acute exposure to these congeners in animals.

U.S. National Toxicology 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

Intermediateduration exposure of humans to PCDDs has occurred after industrial accidents or in population groups exposed to herbicides contaminated by dioxins. Hepatic and dermal changes were the main effects noted, and an association between incidence of diabetes and exposure to 2,3,7,8TCDD has been reported.
The main adverse effects in animals following intermediateduration oral and dermal exposure to 2,3,7,8TCDD included chloracne, wasting syndrome, and liver effects. Similar effects were observed with a mixture of 1,2,3,6,7,8HxCDD and 1,2,3,7,8,9HxCDD, and 1,2,3,7,8PeCDD and 1,2,3,4,7,8HxCDD.
As with acuteduration exposure, the immune system proved to be a very sensitive end point for intermediateduration exposure to 2,3,7,8TCDD, and an intermediateduration oral MRL was derived from a NOAEL value for immunological effects. No data were located regarding toxicity or toxicokinetics in animals after intermediateduration inhalation exposure to PCDDs.

A number of epidemiology studies have examined the toxicity of dioxins following chronic exposure to phenoxy herbicides and chlorophenols contaminated with 2,3,7,8TCDD. Although a number of effects have been observed, interpretation of the results is confounded by a number of factors including lack of adequate exposure information, long post exposure periods, concomitant exposure to other chemicals, and small cohorts.
Hepatic effects were observed in animals after chronic exposure to PCDDs (including 2,3,7,8TCDD, mixed HxCDD isomers, and 2,7DCDD) by the oral route and to 2,3,7,8TCDD by the dermal route. The 2,3,7,8TCDD congener was the most toxic. Studies in monkeys demonstrated their high susceptibility to 2,3,7,8TCDDinduced toxicity. Developmental behavioural effects were seen in offspring of monkeys chronically exposed to low oral doses. The lowest dose tested in this series of studies was used to derive a chronicduration oral MRL.
No studies were located regarding chronic effects of dioxin exposure by the inhalation route. Toxicokinetic inhalation data and chronicduration studies would be useful for assessing the risk levels for people living near municipal, medical, and industrial waste incinerators who can be exposed for chronic durations to PCDDs by this route.

 


Structure formula of 2,3,7,8-Tetrachlorodibenzo-p-dioxin


3D structure of 2,3,7,8-Tetrachlorodibenzo-p-dioxin