Table 10.

Summary of the behavioural studies of HBCDDs in experimental animals

Test compound	Species	Exposure	Outcome	NOAEL/LOAEL	Reference
HBCDDs (3% α‐, 8% β‐ and 89% γ‐HBCDD, as reported in Fång, 2007) Purity: > 98% (prepared from a commercial mixture by the research group of Professor Bergman at the Department of Environmental Chemistry, Stockholm University)	Mice (NMRI) M Neonatal pups	Gavage, at PND10 0, 0.9, 13.5 mg/kg bw (single dose) Vehicle: fat emulsion	Spontaneous behaviour, spatial learning and memory were assessed at age 3 months. At 0.9 and 13.5 mg/kg bw, decreased horizontal locomotion and rearing. Impaired spatial learning and memory (as observed in a Morris water maze) at 13.5 mg/kg bw but not 0.9 mg/kg bw.	LOAEL for spontaneous behaviour = 0.9 mg/kg bw	Eriksson et al. (2006)
HBCDDs Purity: ≥ 95% (Sigma‐Aldrich) No information on stereoisomer composition	Rats (Long‐Evans) M, F pregnant 8–11 animals/group	Gavage, from GD1 to PND0 0, 3, 10, 30 mg/kg bw per day Vehicle: corn oil Litters normalised to 8.	Multiple neurobehavioural tests performed on offspring at different ages up to 21 months. HBCDDs produced age‐related effects at 3 mg/kg bw per day (increased reactivity to a tail pinch in neonates, decreased forelimb grip strength in juveniles, impaired sustained attention and progressive loss of hind leg function in aged rats). No effect on locomotor activity.	No clear dose–response relationships.	Miller‐Rhodes et al. (2014)
α‐HBCDD Purity: 99.3% (produced by transformation of γ‐HBCDD by heat treatment, followed by purification)	Rats (Wistar) F n = 6	Gavage of hen's egg produced by feeding hens with α‐HBCDD, from GD0 to PND21 0, 22, 66 ng/kg bw/day Not stated whether litters were normalised	Decreased pup weight at 22 ng/kg bw per day, associated with impaired motor activity and decreased anxiety. No effects at 66 ng/kg bw per day.	No clear dose–response relationships	Maurice et al. (2015)
HBCDDs Purity: not reported (Sigma) No information on stereoisomer composition	Rats (Sprague Dawley)b Sex not specified 10 days of age 9 animals/group	Gavage, from PND10 to PND70 0.3, 3, 30 mg/kg bw per day 30 mg/kg HBCDD + 300 mg/kg bw per day taurine	Impaired spatial learning and memory in the Morris water maze test. Expression of BDNF, NGF and FGFc in the hippocampus increased at low dose (adaptive) and impaired at higher doses. Taurine appeared to be protective when co‐administered.	Not identified due to limitations in the study (see study description above)	Zhang et al. (2017a)
HBCDDs Purity: not reported (Sigma‐Aldrich) No information on stereoisomer composition	Mice (C57BL/6J) M 4 animals/group (control), 6 animals/group (treatment)	Gavage, 6 weeks 0, 25 mg/kg bw per day From 2 months old Controls: corn oil	Decreased expression of presynaptic, but not post‐synaptic, dopaminergic proteins in hypocampus. No overt behavioural abnormalities (such as deficits in grooming, isolation, feeding or generalised movement.	LOEL = 25 mg/kg bw per day	Pham‐Lake et al. (2017)

F: female; M: male. BDNF: brain‐derived neurotropic factor; NGF: Nerve growth factor; FGF: Fibroblast growth factor; PND: postnatal day; GD: gestational day.

^aIn the absence of factors for converting concentrations in feed into daily doses for pregnant rats, the default factor of 0.12 for subactute studies in rats was used (EFSA Scientific Committee, 2012).

^bThe manuscript sometimes refers to mice, which is assumed to be an error.

^cExpression of specific FGF forms was not investigated.