Polychlorinated Dibenzodioxins and Polychlorinated Dibenzofurans - PSL1

Kinetics and Metabolism

When mixtures of dioxins and furans enter living tissue, those compounds with chlorine in the 2, 3, 7 and 8 positions are the ones most predominantly absorbed and retained. They are most highly concentrated in body fat and in fatty organs such as the liver. While they can be metabolized and excreted, this is a relatively slow process in humans. Half-lives are several years. Their excretion in breast milk can significantly affect the body burden of both the mother (as a source of elimination) and the breast-fed infant (as a source of exposure).

In experimental studies, the absorption of dioxins and furans varies, depending on the medium in which they are administered, the specific compound involved and whether exposure took place through the mouth, skin or lungs.²⁸ Examples include: rats exposed orally to 2,3,7,8-tetrachlorodibenzodioxin absorb 70 to 80 percent of a dose delivered in oil; 50 to 60 percent of a dose mixed in food; 10 to 20 percent of a dose in soil or fly ash; and virtually none of a dose absorbed onto activated carbon. The higher chlorinated dioxins and furans that have been tested seem to be less well absorbed than 2,3,7,8-tetrachlorodibenzodioxin.

In general, absorption is greater when dioxins and furans are ingested than when applied to the skin. Absorption by the lung is probably high but inadequately tested. Human absorption is probably similar to that demonstrated in animal studies. A recent study²⁹ estimated that 87 percent of a 1.14 nanogram per kilogram dose of 2,3,7,8-tetracblorodibenzodioxin ingested by a volunteer was absorbed.

When dioxins or furans are absorbed into the body, they are distributed to a variety of tissues. The liver and fat tissues are the major storage sites in all animal species, including humans.³⁰ Small amounts may also be found in skin, muscle and other organs. Dioxins and furans tend to be found in concentrations in different tissues within the body in proportion to the fat content of the tissue. Distribution of the specific dioxins and furans is dependent on the route of exposure, the amount of exposure and the length of time since exposure began.

The metabolism of dioxins and furans has been studied in laboratory animals but not in humans. While similar paths of metabolism exist in most animals studied, including fish, the rates at which metabolism occurs vary among species.³¹ Rats metabolize 2,3,7 ,8-tetrachlorodibenzodioxin relatively readily, mice and monkeys, less readily, and metabolism by guinea pigs is quite limited. The furans that have been studied appear to be metabolized by similar pathways to the dioxins. Octachloro-dioxin and -furan are not readily broken down in the body.

The rate at which dioxins or furans are eliminated from the body varies from species to species.³¹ However, the route of elimination is predominantly the same across species, i.e. the faeces. For most test animals 50 to 80 percent of an administered dose of 2,3,7,8-tetrachlorodibenzodioxin is excreted in the faeces. A lesser amount is excreted in urine. A single dose of octachloro-dibenzodioxin tends to be excreted virtually unchanged, reflecting its poor absorption into the body following ingestion and its resistance to metabolic degradation. Breast milk can be a significant route of elimination, because its high fat content allows the dioxins and furans to dissolve in the fat and leave the body with the milk. Such elimination can significantly lower the body burden of nursing mothers, but the dioxins and furans will be absorbed by their infants.

Whole-body half-lives have been estimated for 2,3,7,8-tetrachlorodibenzo-dioxin in several test species.³¹ These estimates are similar for rats (range: 17.4 to 31 days) and mice (9.6 to 24.4 days), similar or longer for guinea pigs (22 to 93.7 days), and somewhat shorter for hamsters (12.0 to 15.0 days). Monkeys appear to excrete 2,3,7,8-tetrachlorodibenzodioxin much more slowly, with a half-life of approximately one year.³² Furan compounds are eliminated more rapidly than the corresponding dioxins, i.e. those with the same substitution pattern.

In humans, the half-life of 2,3,7,8-tetrachlorodibenzodioxin has been estimated to be 5.8 years³³ and between 5 and 8 years.³³ The half-life for 2,3,7,8-tetrachlorodibenzofuran in humans is somewhat shorter (1 to 2 years).

²⁸ WHO, 1989 (in press).

²⁹ Poiger and Schlatter, 1986.

³⁰ OME, 1985; WHO, 1989 (in press).

³¹  WHO, 1989 (in press).

³²  McNulty et al., 1982.

³³ Poiger and Schlatter, 1986.

³⁴  Ryan and Norstrom (in press).