# Difference between revisions of "Infant's indirect exposure"

## Question

How to measure infant's dioxin exposure due to fetal period and breast feeding?

Mother's exposure at level 100 pg /d (fairly typical amount) will lead to child's TEQ concentration of 44 pg /g fat (logTEQ 3.8).

 # This is code Op_en7797/ on page [[Infant's dioxin exposure]] library(OpasnetUtils) objects.latest("Op_en7797", code_name="initiate") exposure <- Ovariable("exposure", data = data.frame(Exposure_agent = "TEQ", Result = 100)) dx.expo.child <- EvalOutput(dx.expo.child) oprint(summary(dx.expo.child)) 

## Rationale

The equations and code below was developed for dioxins, but later it was extended to perfluorinated alkyl substances (PFAS) as well.

Transformation between serum concentration and intake: $C_s = \frac{I * t_{1/2} * f}{a * ln2 * BF%},$
where
Cs = serum concentration of compound in pg/g fat
I = average daily intake of compound in pg/kg/day
t1/2 = the half-life of compound (2737.5 d = 7.5 a)
f = fraction of ingested compound actually absorbing from the gut (0.80)
BF% = body fat percentage
a percentage of total daily dietary intake of compounds that come from fish (0.86).


The previous equation applies in a single individual. In the case of dental aberrations, the main exposure comes from the mother during pregnancy and breast feeding. For this, we use $C_{s,i} = \frac{I_{a,m} * t_{1/2,m} * f_m * FE}{ln2 * BF_i},$
where
Cs,i = serum concentration of compound in the infant in pg/g fat
Ia,m = average daily intake of compound of the mother in absolute amounts pg/day
t1/2,m = the half-life of compound in the mother (2737.5 d = 7.5 a)
fm = fraction of ingested compound actually absorbing from the gut in the mother (0.80)
FE = fraction of mother's compound load that is transported to the infant during breast feeding (0.25) Vartiainen et al. REF
BF = body fat amount in the infant (into which the compound is evenly distributed) during the period when tooth are sensitive to defects and the exposure at its highest (ca. six months of age) (1 kg)


With dioxin, body fat represents the distribution volume, as the compound distributes evenly in the fat compartments of the body. Therefore, the dioxin concentration per gram fat is approximately the same in blood and fat tissue. With PFAS, the concentration in blood equals total amount divided by the distribution volume.

### Inputs

Parameters(-)
ObsExposure_agentParameterValueDescription
1TEQhalf-life2737.5t0.5: 7.5 * 365, Dioxin half-life in adults (d)
2TEQfraction absorbed0.6 - 0.8f_ing: 0.70, Fraction of compound ingested that is actually absorbed (-). Adjusted downwards to reflect KTL sarcoma study concentrations
3TEQfraction to child0.05 - 0.1f_mtoc: 0.075, Fraction of mother's compound burden that enters the child during breast-feeding in 6 mo. Alaluusua et Vartiainen used 0.25 but that produces way too high predictions (-)
4TEQdistribution volume in infant1580BF: 0.2 * (7.692+8.141) / 2, body fat amount in the infant at six months of age (g) [[:op_en:Body weight of 0-24 months old Finnish children]].
5PFAShalf-life1642.5 (912.5 - 3285)t0.5: 4.5 (2.5 - 9) a * 365, PFOS half-life in adults (d), EFSA, slightly adjusted
6PFASfraction absorbed0.1 - 0.15f_ing: 0.80, Fraction of compound ingested that is actually absorbed (-) See below.
7PFASfraction to child0.2 - 0.4f_mtoc: 0.25, Fraction of mother's compound burden that enters the child during breast-feeding in 6 mo. Alaluusua et Vartiainen (-)
8PFASdistribution volume in infant1580BF: 200 ml/kg for PFOS * (7.692 kg + 8.141 kg) / 2, body fat amount in the infant at six months of age (g) [[:op_en:Body weight of 0-24 months old Finnish children]].

#### PFAS kinetics

ccording to EFSA, a long-term exposure of 4.4 ng/kg/d to PFAS leads to 6.9 ng/ml in blood. This implies that fm = 6.9 ng/ml / 4.4 ng/kg/d / 1642 d * 200 ml/kg * ln2 = 13 % of PFAS is actually absorbed by the mother.

This in turn leads to PFAS concentration of 17.5 ng/ml blood in the child, i.e. ca 2.5-fold compared with the mother. This implies that FE = cs,i / amount in mother * BFi = 17.5 ng/ml / (6.9 ng/ml * 200 ml/kg * 70 kg) * (200 ml/kg * 8 kg) = 0.29.

### Calculations

• Ovariables initiated 19.5.2017 
• Updated 30.5.2017 
• This code was called initiate with dx.expo.child until 13.6.2019. Now it has expo_indir for indirect exposure estimates. Indirect here means that the exposure is not directly estimated from environmental concentrations but indirectly from mother's exposure.
• An updated code expo_indir2 includes PFAS as well as dioxin. 2021-01-20 

 # This is code Op_en7797/expo_indir2 on page [[Infant's dioxin exposure]] library(OpasnetUtils) ################## CREATE a separate ovarible about children's exposure via mother's milk. # Convert mother's compound intake (pg/d) into child's compound concentration (pg/g) in fat after 6 months of breast-feeding. # For details, see [[ERF of dioxin#Dental defects]] and [[:op_fi:PFAS-yhdisteiden tautitaakka]] a <- opbase.data("Op_en7797", subset = "Parameters") # [[Infant's dioxin exposure]] t0.5 <- Ovariable("t0.5", data = a[a$Parameter == "half-life" , ][-c(1,3)]) f_ing <- Ovariable("f_ing", data = a[a$Parameter == "fraction absorbed" , ][-c(1,3)]) f_mtoc <- Ovariable("f_mtoc", data = a[a$Parameter == "fraction to child" , ][-c(1,3)]) BF <- Ovariable("BF", data = a[a$Parameter == "distribution volume in infant" , ][-c(1,3)]) expo_indir <- Ovariable( "expo_indir", dependencies = data.frame( Name = c( "expo_dir", # Mother's exposure to compound (pg/d) "t0.5", # Half-life of compound in mother (d) "f_ing", # Fraction of compound ingested by mother that is actually absorbed "f_mtoc", # Fraction of mother's compound body burden that enters the child during 6 mo breast feeding. "BF" # Distribution volume (ml) (or body fat amount (g) re dioxin) in the infant at 6 mo of age ) ), formula = function(...) { out <- expo_dir * f_ing * t0.5 / log(2) # Body burden in mother after long constant exposure out <- out * f_mtoc / BF # compound concentration in child (per g fat or ml blood) out\$Exposure <- "To child" return(out) } ) objects.store(t0.5, f_ing, f_mtoc, BF, expo_indir) cat("Ovariables t0.5, f_ing, f_toc, BF, expo_indir stored.\n")