Dioxin exposure-response function on population level

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Scope

Dioxin exposure-response function on population level. R↻ . General population average.

Definition

Human health effects caused by dioxins

Dioxins are persistent environmental pollutants and they accumulate in the food chain. Dioxins cause a large variety of effects in laboratory animals. They are carcinogenic at large doses, and they also cause developmental defects. The evidence of human effects has been more limited, because the exposure levels have been much lower than in animal tests. However, an increased cancer risk has been observed after high industrial occupational exposures. In addition, mild tooth mineralisation defects have been observed in children in Finland, even after typical exposures of the 1980's. Children are exposed to dioxins mostly via mother's milk. The dioxin levels have been decreasing since then, and no tooth defects have been observed at the current exposure levels.

Dioxins are a group of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). They are persistent environmental contaminants that accumulate in the human body. Their elimination half-life is quite high (~7 years). 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic PCDD/Fs congener, and it is classified as a known human carcinogen by the International Agency for Research on Cancer (IARC).

• Health effects related to long-term exposure
  • impairment of the immune system
  • impairment of the developing nervous system
  • impairment of the endocrine system
  • impairment of reproductive functions
  • increased cancer risk

Evidence concerning cancer risk is mainly from animal studies, and dioxins are probably quite weak carcinogens in humans. Hormesis type of dose-response is suspected. Evidence concerning other health effects is inconsistent.

In this specific case

• MSWI is likely to increase background dioxin exposure (additional low exposure)
• the risk of accidental exposure is low (dioxin emissions will increase only if burning process is working improperly)
• health effects of long-term exposure are relevant
• effects on development and endocrine functions are more relevant than the risk of cancer
• The health effects of low doses should be modelled from animal and human data. Eg. Alaluusua et al. (1996) have studied tooth development. In a study by Miettinen et al. (2005), exposure to 0.5 μg TCDD/kg body weight on GD 15 resulted in maternal adipose tissue concentration of 2185 pg/g fat. In that study, linear extrapolation of the data predicts a maternal adipose tissue concentration of 100-120 pg/g fat after exposure to 0.03 μg TCDD/kg body weight. This estimated maternal adipose tissue concentration is sufficient to induce developmental dental defects in rat offspring, and is similar to the highest values measured in the Finnish average population (PCDD/F 145.5 pg WHO-TEQ/g fat (Kiviranta et al. 2005).

Sensitive subgroups: foetuses, newborns, young females (women below or at childbearing age), individuals with high fish consumption (e.g. fishermen), individuals working in incineration plants etc.

Tolerable daily intake (TDI): 1-4 pg/kg body weight

U.S.EPA estimates the dioxin and other cancer potencies by using cancer slope factors (CSFs). CSF for dioxins is 156000 kg*d/mg [1]. This estimate has often often considered as overestimate, as the aim is to produce conservative assessments (where false positive is better than a false negative). It has also been suggested that dioxin cancer response is secondary to toxicity and has a threshold, below which cancer risk does not exist. World health organisation has approached dioxin risks from another endpoint, namely developmental defects. WHO has assessed that there is a threshold below which developmental defect risk is negligible. A tolerable daily intake is 1-4 pg/kg/d, and the average Finnish average is close to this or slightly below. In this draft assessment we will use both approaches. The U.S.EPS approach gives a higher value for risks and thus produces the plausible upper end of the confidence interval.

References

• Alaluusua et al. Eur J Oral Sci. 1996 Oct-Dec;104(5-6):493-7.
• Crump et al. 2003. Meta-analysis of dioxin-cancer dose-response for three occupational cohorts. Environmental Health Perspectives 111 (5), 681-687.
• Kiviranta et al. Chemosphere. 2005 Aug;60(7):854-69.
• Kogevinas 2001. Human health effects of dioxins: cancer, reproductive and endochrine system effects. Human Reproduction Update 7 (3), 331-339.
• Miettinen HM et al. Toxicol Sci. 2005 Jun;85(2):1003-12.
• Tuomisto JT et al. Int J Cancer. 2004 Mar 1;108(6):893-900.
• Tuomisto et al. 1999. Synopsis on dioxins and PCBs. Publications of the National Public Health Institute B17/1999.
• van Leeuwen FX et.al. Chemosphere. 2000 May-Jun;40(9-11):1095-101.

Data

Effective dose resulting in a 0.01 increase in lifetime risk of cancer mortality (ED₀₁): 45 ng/kg body weight (95% CI 21-324 ng/kg body weight).

= 0.01/(45 pg/(kg body weight * 200 g body fat/kg body weight))

= 0.044 /(pg/g body fat)

Unit

Increased incidence/(pg/g body fat)

Result

For cancer risk: 0.044