A PBPK model to study the transfer of α-hexabromocyclododecane (α-HBCDD) to tissues of fast- and slow-growing broilers

Figures & data

Figure 1. Simplified representation of the PBPK model simulating the absorption/metabolism/elimination (solid grey), blood distribution (solid black), direct uptake from liver through lipid deposition (dotted black), and passive diffusion in tissues (dotted grey) of α-HBCDD in growing broilers.

Table 1. Parameters of the model for fast-(FG) and slow-(SG) growing broilers. In brackets, parameter values after optimisation.

Acronym	Description	Unit	Value
			FG	SG
Age1	Initial age	d	0
Age2	Final age	d	42	84
BW1	Initial body weight	kg	0.042	0.050
BW2^1	Final body weight	kg	2.90	2.20
Bgomp^1	Growth rate at the inflection point of the Gompertz body growth function	d^−1	0.0453	0.0287
a intake^1	Slope of the allometry between feed intake and body weight	Dl	0.273	0.145
b intake^1	Intercept of the allometry between feed intake and body weight	Dl	0.556	0.942
a Breast^2	Slope of the allometry between breast muscles and body weights	Dl	2.42	1.17
			1.30
b Breast^2	Intercept of the allometry between breast muscles and body weights	Dl	0.00	-2.47
			-1.96
a Leg	Slope of the allometry between leg muscles and body weights	Dl	1.06	1.15
b Leg	Intercept of the allometry between leg muscles and body weights	Dl	-1.99	-1.99
a Blood	Slope of the allometry between blood and body weights	Dl	0.842
b Blood	Intercept of the allometry between blood and body weights	Dl	-2.60
a Liver^3	Slope of the allometry between liver and body weights	Dl	1.28/0.79
b Liver^3	Intercept of the allometry between liver and body weights	Dl	0.79/-3.55
a BL^1	Slope of the allometry between body lipids and body weights	Dl	1.21	1.26
b BL^1	Intercept of the allometry between body lipids and body weights	Dl	-2.32	-2.2
a storagefat	Slope of the allometry between storage fat and body lipids weights	Dl	1.44	1.66
b storagefat	Intercept of the allometry between storage fat and body lipids weights	Dl	0.432	0.852
Prop Skin	Proportion of skin in storage fat	Dl	0.66
Prop Storagefatperf	Final proportion of perfused storage fat	Dl	0.30 (0.33)
Breast lipid conc	Concentration of lipids in breast muscles	kg kg^−1	0.0127
Leg lipid conc	Concentration of lipids in leg muscles	kg kg^−1	0.034	0.054
Plasma lipid conc	Concentration of lipids in plasma	kg L^−1	0.004
Liver lipid conc	Concentration of lipids in liver	kg kg^−1	0.0535
Skin lipid conc	Concentration of lipids in skin	kg kg^−1	0.40
SFD gain lipid conc ini	Initial concentration of lipids in separable fat depots gain	kg kg^−1	0.60	0.40
SFD gain lipid conc fin	Final concentration of total lipids in separable fat depots gain	kg kg^−1	0.90
SFD lipid conc age	Age at which increase in the concentration of lipids in the separable fat depots gain stops	d	14	28
a Breast neut lipid	Proportion of neutral lipids in total lipids of breast muscles	Dl	0.62 (0.23)
a Leg neut lipid	Proportion of neutral lipids in total lipids of leg muscles	Dl	0.78
a Plasma neut lipid	Proportion of neutral lipids in total lipids of plasma	Dl	0.32 (0.20)
a Liver neut lipid	Proportion of neutral lipids in total lipids of liver	Dl	0.55 (0.38)
a Storagefat neut lipid	Proportion of neutral lipids in total lipids of storage fat (Skin and SFD)	Dl	1
a Other neut lipid	Proportion of neutral lipids in total lipids of other tissues	Dl	0.80 (0.50)
a Q	Slope of the allometry between cardiac output and body weight	Dl	0.856
b Q	Intercept of the allometry between cardiac output and body weight	Dl	5.55
Breast perf	Perfusion rate of breast muscles	L kg^−1 d^−1	140
Leg perf	Perfusion rate of leg muscles	L kg^−1 d^−1	190
Liver perf	Perfusion rate of liver	L kg^−1 d^−1	1200 (500)
Skin perf	Perfusion rate of skin	L kg^−1 d^−1	100 (160)
SFD perf	Perfusion rate of separable fat depots	L kg^−1 d^−1	100 (200)
Diff Storagefat coef	Coefficient of diffusion of α-HBCDD from perfused to deep storage fat	d kg^−1	200 (168)
Ht	Hematocrit	Dl	0.274
mV blood	Volumetric mass of blood	kg L^−1	1.044
HBCDD abs coef	Coefficient of absorption of α-HBCDD	Dl	0.90 (0.79)
Clip^4	Intrinsic clearance rate of (+)-α-HBCDD	d^−1	12.0 (15.12)
Clin^4	Intrinsic clearance rate of (−)-α-HBCDD	d^−1	9.6 (10.8)
EF diet	α-HBCDD enantiomeric fraction of the contaminated diet	Dl	0.504
Diff Faeces coef	Coefficient of diffusion of α-HBCDD from plasma to faeces	d kg^−1	200 (125)
Feed lipid conc age	Age at which the lipid concentration in feed changes	d	14	21
Feed lipid conc ini4	Lipid concentration in feed for age ≤ Feed lipid conc age	kg kg^−1	0.067	0.087
Feed lipid conc fin	Lipid concentration in feed for age > Feed lipid conc age	kg kg^−1	0.067	0.055
Feed DM conc	Dry matter concentration in feed	kg kg^−1	0.88
Dig DM	Digestibility of feed dry matter	Dl	0.67
Faeces DM conc	Dry matter concentration in faeces	kg kg^−1	0.24
Dig lipid	Digestibility of feed lipids	Dl	0.84

Dl: Dimensionless.

^aValues are presented for as hatched broilers. Values for each sex are given in Supplemental Material S1.

^bParameter values for body weight < and ≥ 0.172 kg, respectively.

^cParameter values for body weight < and ≥ 0.162 kg, respectively.

Table 2. Fast- (FG) and slow-growing (SG) broilers exposed to α-HBCDD through a contaminated feed (38 µg α-HBCDD kg⁻¹) from hatching to slaughter: main characteristics of broilers, assimilation efficiency (AE) and accumulation ratio (AR) of α-HBCDD at slaughter.

Strain	FG	SG
Animal characteristics^a
Age (d)	42 (36–54)	84 (81–95)
Body weight (BW, kg)	2.9 (1.8–3.4)	2.2 (1.9–3.5)
Body lipids (g kg^−1 BW)	130	136
Feed intake (kg)	4.53	6.37
Feed efficiency	0.640 (0.444–0.688)	0.345 (0.262–0.470)
α-HBCDD AE^b	0.36	0.22
α-HBCDD AR^c
Body	0.56	0.65
Breast	0.015	0.016
Breast + Skin^d	0.33	0.32
Leg	0.14	0.24
Leg + Skin^d	0.46	0.53
Skin	2.4	2.4
Separable Fat Depots (SFD)	5.4	5.3

^aAs hatched; in brackets, intervals according to production statistics provided by one of the co-authors of this paper (A. Travel, ITAVI).

^bRatio of the amount in the body to the amount ingested.

^cRatio of the concentration of α-HBCDD in the tissue on a fresh weight (fw) basis (µg kg⁻¹ fw) to its concentration in feed (µg kg⁻¹ fw).

^dProportions of muscle and of skin: Breast + Skin, 87% and 13%, respectively; Leg + Skin, 86% and 14%, respectively (Shahin and Abd Elazeem 2005; Haitook 2006).

Figure 2. Observed and simulated α-HBCDD concentration (ng g⁻¹ lipid weight)¹ and enantiomeric fraction (EF)² in tissues of broilers exposed to a contaminated feed (38 µg α-HBCDD kg⁻¹). (a): slow-growing broilers exposed during 42 days and then decontaminated during 42 days (used for optimisation); (b): slow-growing broilers exposed during 84 days; (c): fast-growing broilers exposed during 42 days.

Figure 3. Simulated kinetics of α-HBCDD accumulation ratio (ARlip)¹ in tissues of fast- (FG) and slow-growing (SG) broilers² exposed through feed (38 µg α-HBCDD kg⁻¹) from hatching to slaughter.

Figure 4. Assimilation efficiency (AE)¹ and accumulation ratio (AR)² of α-HBCDD in tissues of fast- (FG) and slow-growing (SG) broilers³ exposed through feed (38 µg α-HBCDD kg⁻¹) from hatching to slaughter according to their age (Age, d) and body weight (BW, kg) at slaughter.

Table 3. Final concentrations, mean decontamination and elimination rates of α-HBCDD in tissues of fast- (FG) and slow-growing (SG) broilers^a contaminated either through feed^b or extruded polystyrene^c (XPS) consumption.

Strain	FG				SG
Exposure source		XPS
Scenario	Feed	A	B	C	Feed
Body weight (kg)^d	0.04–0.89	0.34–0.44	0.74–0.89	1.3–1.5	0.05–0.92
α-HBCDD ingested (µg)	38	172	172	172	67
Final α-HBCDD concentration (µg kg^−1 lw)
Breast	46	18	27	36	4
Leg	159	64	98	131	13
Skin	229	111	172	229	21
Decontamination rate (kc, d^−1)
Breast	−0.045	−0.035	−0.043	−0.056	−0.022
Leg	−0.045	−0.035	−0.045	−0.058	−0.022
Skin	−0.044	−0.036	−0.043	−0.050	−0.022
Elimination rate (kw, d^−1)
Breast	−0.027	−0.025	−0.028	−0.035	−0.019
Leg	−0.033	−0.028	−0.034	−0.042	−0.019
Skin	−0.007	−0.006	−0.004	−0.002	−0.011
Contribution of lipid deposition to decontamination rate (%)
Breast	39	29	36	37	13
Leg	27	19	24	28	14
Skin	85	84	90	97	51

lw: lipid weight.

^aBroilers characteristics are detailed in Table 2.

^bThe feed contains 38 µg α-HBCDD kg⁻¹ and is consumed between from hatching to 21 and 42 days of age in FG and SG broilers, respectively.

^cExposure through the ingestion of 57.3 µg α-HBCDD daily during 3 days from 12 to 14 (A), 19 to 21 (B) or 26 to 28 (C) days of age.

^dBody weights at the beginning and end of the contamination period.

Figure 5. Simulated kinetics of α-HBCDD burden (µg) (a) and accumulation ratio (ARlip)¹ (b) in tissues of fast- (FG) and slow-growing (SG) broilers² exposed through feed (38 µg α-HBCDD kg⁻¹) from hatching to 21 and 42 days, respectively. Mean decontamination (kc) and elimination (kw) rates are presented in Table 3.

Figure 6. Simulated kinetics of α-HBCDD concentration (µg kg⁻¹ lw) in breast, leg and skin of fast-growing broilers¹ ingesting 172 µg α-HBCDD according to different modalities of exposure: 42-day exposure through feed containing 38 α-HBCDD µg kg⁻¹ (Feed) or exposure through the daily ingestion of 57.3 µg α-HBCDD (extruded polystyrene) during 3 days from 12 to 14 (a), 19 to 21 (b) or 26 to 28 (c) days of age^2,3.

Shahin KA, Abd Elazeem F. 2005. Effects of breed, sex and diet and their interactions on carcass composition and tissue weight distribution of broiler chickens. Archiv Für Tierzucht. 48:612–626.

 Web of Science ®Google Scholar

Haitook T. 2006. Study on chicken meat production for small-scale farmers in northeast Thailand. J Agric Rural Dev Tropics Subtropics. 87(Suppl):1–164.

 Google Scholar