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Updated: May 31, 2026
Determining Bile Duct Density in the Mouse Liver
Published on: April 30, 2019
Differences in tissue distribution of HBCD alpha and gamma between adult and developing mice
David T Szabo1, Janet J Diliberto, Janice K Huwe
1University of North Carolina-Chapel Hill Curriculum in Toxicology, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. Szabo.David@epa.gov
Insights
Developing mice show higher Hexabromocyclododecane (HBCD) body burden than adults, with α-HBCD accumulating more than γ-HBCD. This suggests developmental stage is a critical factor in HBCD toxicity and exposure risks.
Area of Science:
- Environmental Science
- Toxicology
- Developmental Biology
Background:
- Hexabromocyclododecane (HBCD) is a flame retardant mixture with three stereoisomers: α-HBCD, β-HBCD, and γ-HBCD.
- While γ-HBCD dominates production, α-HBCD is more prevalent in biotic samples, raising concerns about its toxicokinetics.
- Infants and young children are considered susceptible populations due to potential adverse developmental effects and higher exposure estimates.
Purpose of the Study:
- To investigate and compare the toxicokinetics and tissue distribution of α-HBCD and γ-HBCD in infantile mice.
- To determine if developmental stage influences HBCD disposition and body burden.
- To assess potential differences in HBCD accumulation between developing and adult mice.
Main Methods:
- Single oral dose administration of α-[(14)C]HBCD or γ-[(14)C]HBCD (3 mg/kg) to postnatal day 10 C57BL/6 mice.
- Monitoring of tissue distribution and internal dosimetry up to 7 days postexposure.
- Comparison of radioactivity levels in various tissues between infantile and adult mice.
Main Results:
- Developing mice exposed to α-HBCD had a higher overall body burden (22% at 4 days) compared to those exposed to γ-HBCD (10%).
- Infantile mice exhibited significantly higher total body burden for both isomers (10-fold for γ-HBCD, 2.5-fold for α-HBCD) than adult mice.
- Higher concentrations of both α-HBCD and γ-HBCD-derived radioactivity were found in key tissues (liver, fat, kidney, brain, blood, muscle, lungs) of pups compared to adults.
Conclusions:
- The toxicokinetics of α-HBCD and γ-HBCD differ between developing and adult mice, with pups accumulating higher concentrations.
- Distribution patterns are similar, but absolute levels are elevated in infantile mice, particularly in target organs.
- Developmental stage is identified as a significant risk factor for HBCD toxicity, as developing animals exhibit increased sensitivity and body burden.
Abstract:
Hexabromocyclododecane (HBCD) is a mixture of three stereoisomers alpha (α), beta (β), and gamma (γ). γ-HBCD dominates the mixture (∼70%), and despite α-HBCD's minor contribution to global HBCD production and usage (∼10%), it is the dominant congener found in most biotic samples worldwide. Evidence of toxicity and lack of stereoisomer studies drives the importance of understanding HBCD toxicokinetics in potentially susceptible populations. The majority of public health concern has focused on hazardous effects resulting from exposure of infants and young children to HBCD due to reports on adverse developmental effects in rodent studies, in combination with human exposure estimates suggesting that nursing infants and young children have the highest exposure to HBCD. This study was designed to investigate differences in the disposition of both γ-HBCD and α-HBCD in infantile mice reported to be susceptible to the HBCD commercial mixture. The tissue distribution of α-[(14)C]HBCD- and γ-[(14)C]HBCD-derived radioactivity was monitored in C57BL/6 mice following a single oral dose of either compound (3 mg/kg) after direct gavage at postnatal day 10. Mice were held up to 7 days in shoebox cages after which pups were sacrificed, tissue collected, and internal dosimetry was measured. Developing mice exposed to α-HBCD had an overall higher body burden than γ-HBCD at every time point measured; at 4 days postexposure, they retained 22% of the α-HBCD administered dose, whereas pups exposed to γ-HBCD retained 10%. Total body burden in infantile mice after exposure to γ-HBCD was increased 10-fold as compared with adults. Similarly, after exposure to α-HBCD, infantile mice contained 2.5-fold higher levels than adult. These differences lead to higher concentrations of the HBCD diastereomers at target tissues during critical windows of development. The results indicate that the toxicokinetics of the two HBCD diastereomers differ between developing and adult mice; whereas distribution patterns are similar, concentrations of each HBCD diastereomer's-derived radioactivity are higher in the pup's liver, fat, kidney, brain, blood, muscle, and lungs than in the adult's. This study suggests that developmental stage may be a risk factor for the harmful effects of α-HBCD and γ-HBCD, when developing animals may be more sensitive to effects and have increased body burden.
