ERF of dioxin on dental aberrations

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• ERF of TCDD

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Question

What is the quantitative relationship between exposure to TCDD during infancy and childhood and the risk (probability) of developmental dental defects described as defects of tooth enamel? Exposure is expressed in terms of concentration of TCDD in serum lipid.

Answer

Resulting distribution based on one simulation.

Weibull(alfa=0.2925,beta=2.192)

Rationale

ERF of dioxin on dental aberrations is a continuous random variable indexed by age. It applies to the first two age groups of the Beneris population (0-2 and 2-18 years, gender combined). It has been agreed that this ERF can be applied to WHO-TEQ concentration of dioxin (PCDD/F) and dioxin-like PCB in body fat.

Probability distribution of ERF of dioxin on dental aberrations was created based data on dioxin accident in Seveso in 1976 extracted from study by Alaluusua et al. This data is summarized in a table below.

Table: Developmental defects of enamel in individuals who were children (< 5 years of age) at the time of the Seveso accident by exposure group.

Exposure group	Number of exposed individuals	Number of enamel defect cases after 25 years since Seveso accident	Serum TCDD concentration range (pq/g lipid)	Mean serum TCDD concentration (pq/g lipid)	Risk (%)
non-ABR zone	39	10		40.5	26
Exposed group 1	10	1	31-226	128.5	10
Exposed group 2	11	5	238-592	415	45
Exposed group 3	15	9	700-26000	3000	60

It has been assumed that the TCDD exposure in children from the non-ABR zone follows lognormal distribution with mean 40.5 (ng/kg in fat) and geometric standard deviation 4 while the exposure in the remaining groups is log-uniformly distributed over the range of serum levels reported in the table. The log-logistic model (with constant term) was chosen to model the relation between the log-transformed and scaled serum TCDD level and the probability of developmental defects of enamel. The independent variable used was ln(serum TCDD level+1). Probability distribution of the coefficient for the independent variable was constructed using the following approach. Let ni denote number of children in exposure group i and ri be the number of observed enamel defect cases in group i, i= 1,...,4.

1. Sample ni exposures from distribution of TCDD serum level in group i. Denote these exposures as xj, j=1,...,75.
2. Assign ri responses randomly to ni people.
3. Fit the dose-response model to simulated data, call it model p0.
4. Compute predicted probability for every person in the study, i.e. compute p0(xj).
5. Re-sample the response of each person assuming that the probability that person j responds is p0(xj), j=1,...,75.
6. Re-fit the dose-response model.
7. Iterate steps 5-6 100 times.
8. Repeat steps 1 - 7 1500 times.
9. Create the density histogram of simulated estimates of regression coefficient (only positive values are kept).
10. Fit parametric probability density function to the histogram.

Unit

(ln(ng/kg fat))^-1

See also

heande:Exposure-response functions for tooth defects caused by TCDD (children)

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