Gestational exposure to polychlorinated biphenyls and dibenzofurans induced asymmetric hearing loss: Yucheng children study
Introduction
Polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are widespread environmental pollutants. The use of these chemicals are currently banned or restricted in most developed countries. However, because of the chemicals' persistence in the environment, high background concentrations are still found as seen in several large-scale epidemiologic studies in the general population (Patterson et al., 2008, Patterson et al., 2009, Wong et al., 2008). Due to the world-wide ubiquitous background exposure, PCDDs, PCDFs, and PCBs are still a concern to human health. PCBs have been suggested as neurotoxicants especially when exposed during prenatal and early postnatal periods, and known to cause neurological effects including neurocognitive deficits, behavioral problems, and auditory impairments (Boucher et al., 2010, Grandjean and Landrigan, 2006, Schantz, 1996, Schantz et al., 2003, Tilson et al., 1998). We and others have reported neurological adverse effects in the children prenatally exposed to PCBs and PCDFs (Chen et al., 1992; Jacobson and Jacobson, 1996; Lin et al., 2008).
Several animal studies have demonstrated auditory deficits after gestational PCB exposure. In rats, gestational exposure to a commercial PCB mixture, Aroclor 1254, resulted in low-frequency hearing loss (Goldey et al., 1995, Lasky et al., 2002). The rats with gestational exposure to a mixture of 35% Aroclor 1242, 35% Aroclor 1248, 15% Aroclor 1254, and 15% Aroclor 1260 had decreased hearing function as measured by an objective method, distortion product otoacoustic emissions (DPOAE), including reduced amplitudes and elevated thresholds across a wide range of frequencies (Powers et al., 2009, Powers et al., 2006). More recently, a study suggested an additive effect of PCBs and polybrominated diphenyl ethers (PBDEs) on cochlear function, evidenced by reduced DPOAE amplitudes and increased DPOAE thresholds in rats (Poon et al., 2011).
Further investigation on the auditory pathway showed that rats exposed to Aroclor 1254 decreased amplitude of the early brainstem auditory evoked response (BAER) peaks, a measurement for the damage in the brainstem auditory pathways (Herr et al., 1996). The authors suggested that the deficit might exist at the level of the cochlea and/or auditory nerve. A recent study in rats confirmed PCB-52 and PCB-180 effect on elevation BAER threshold. This study also indicated that different PCB congeners had varied potencies, as PCB-52 had greater effect on BAER threshold than PCB-180 (Lilienthal et al., 2011).
In humans, studies on auditory effects of gestational exposure to PCBs are limited. A study in 7-year-old children in Faroe Islands found a positive association between prenatal PCB exposure and auditory thresholds at frequencies 250 and 12,000 Hz in only the left ear (Grandjean et al., 2001). In a follow-up study of mother-child pairs in 12 U.S. centers, higher PCB concentration in maternal serum was related to increased hearing thresholds at 2000 Hz in the left ear, and 4000 Hz in the right ear when the children were 8 years of age (Longnecker et al., 2004). Swedish boys, born to fishermen's wives and sisters in east coast, who were exposed to organochlorine, according to plasma PCBs concentrations (Grimvall et al., 1997, Rylander et al., 1997), had higher prevalence of hearing loss as compared to boys born to fisherman families in west coast, where exposure to PCBs was low. However, somehow conflicting results were also found, that the boys from fisherman's families of east coast did not have poorer hearing ability as compared to the local reference population, who were not highly exposed to PCBs (Rylander and Hagmar 2000).
In 1978–1979, an episode of mass exposure to toxic agents occurred in central Taiwan. Approximately 2000 victims ingested rice oil contaminated with PCBs (Kanechlor-500) and their pyrolytic products (Hsu et al., 1985). After an average of 9–10 months of exposure, the etiology was confirmed by health authority that one specific brand of rice oil was contaminated and was the causal agent of this mass poisoning. Repeated heating of the PCBs resulted in generation of PCDFs and polychlorinated quaterphenyls (PCQs). Based on the interviews with 98 Yucheng patients, average consumption was estimated to be 1 g (range=0.7–1.4) of PCBs and 3.8 mg (range=1.8–5.6) of PCDFs (Lan et al., 1981), averagely. More than 13 years after the Yucheng incident, Yucheng mothers continued to have detectable serum concentrations of PCB/PCDF congeners that were many times higher than that of the unexposed controls (Guo et al., 1997). The children born to mothers exposed to PCBs and related compounds were called Yucheng children. Our previous study showed that Yucheng children had a higher incidence of otitis media than referent children (Chao et al., 1997). No auditory assessment was performed during that time. We therefore conducted a follow-up study to test the hypothesis whether children prenatally exposed to PCBs and PCDFs had higher risk of developing auditory deficits, as compared to their referent children. We also examined whether hearing effects were associated with gestational PCBs/PCDFS exposure or exposure to specific congeners in the Yucheng children.
Section snippets
Subjects
This study was approved by the Institutional Review Board of The National Taiwan University Medical Center. The study candidates were from two groups, the exposed Yucheng children who were born between June 1978 and December 1998 to mothers exposed to PCBs and PCDFs (Chen et al., 1992, Guo et al., 1994). The other group was from the previously identified referent group of children. For each Yucheng child, one unexposed child was selected as a control by matching for neighborhood (lived/born
Results
Among the 184 Yucheng children invited, 86 agreed to participate in this examination. Among the 184 referent children, 97 agreed to participate. The Yucheng and referent children were of similar age, gender, body mass index, total cholesterol, and triglyceride (Table 1). Among Yucheng children, non-participants had average age of 21.3±3.8, 51.0% males. Among referents, non-participants had average age of 21.3±3.8, 51.7% males. These were not different from participants (data not shown).
For pure
Discussion
This is the first paper describing adverse hearing effects in children with gestational exposure to PCBs and PCDFs. The main damage to hearing threshold by such exposure was found at low frequencies. Such damage was related to gestational exposure to 2,3,4,7,8-pnCDF, but not to the marker-PCB congeners.
The mechanism of PCBs-induced auditory deficits has been suggested in prenatally exposed animals. Thyroid hormone is necessary for normal cochlear development (Uziel, 1986), and perinatal
Acknowledgments
This study was supported by Grants NSC102-2314-B-002-069-MY2 and NSC101-2314-B-002-119 from the Ministry of Science and Technology, Taiwan. The authors cordially thank the late Larry L. Needham of the Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, for his great input to this study.
References (49)
- et al.
Prenatal exposure to methylmercury and PCBs affects distinct stages of information processing: an event-related potential study with Inuit children
Neurotoxicology
(2010) - et al.
Hearing loss following exposure during development to polychlorinated biphenyls: a cochlear site of action
Hear. Res.
(2000) - et al.
Thyroxine replacement attenuates hypothyroxinemia, hearing loss, and motor deficits following developmental exposure to Aroclor 1254 in rats
Toxicol. Sci.
(1998) - et al.
Developmental exposure to polychlorinated biphenyls (Aroclor 1254) reduces circulating thyroid hormone concentrations and causes hearing deficits in rats
Toxicol. Appl. Pharmacol.
(1995) - et al.
Dose–response and time course of hypothyroxinemia and hypo-insulinemia and characterization of insulin hypersensitivity in 2,3,7,8-tetrachloro-dibenzo-p-dioxin(TCDD)-treated rats
Toxicology
(1987) - et al.
Developmental neurotoxicity of industrial chemicals
Lancet
(2006) - et al.
Neurobehavioral deficits associated with PCB in 7-year-old children prenatally exposed to seafood neurotoxicants
Neurotoxicol. Teratol.
(2001) - et al.
Early development of Yu-Cheng children born seven to twelve years after the Taiwan PCB outbreak
Chemosphere
(1994) - et al.
Developmental exposure to Aroclor 1254 produces low-frequency alterations in adult rat brainstem auditory evoked responses
Fundam. Appl. Toxicol.
(1996) - et al.
Enzyme induction and alterations in thyroid hormone, vitamin A and K levels by TCDD in neonatal and maternal rats
Chemosphere
(1990)
In utero exposure to polychlorinated biphenyls and sensorineural hearing loss in 8-year-old children
Neurotoxicol. Teratol.
Alterations in rat brain thyroid hormone status following pre- and postnatal exposure to polychlorinated biphenyls (Aroclor 1254)
Toxicol. Appl. Pharmacol.
reference range (PCDDs, PCDFs, cPCBs, mono-PCBs) for the US population 2001–2002
Chemosphere
Thyroid status and thermogenesis in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin
Toxicol. Appl. Pharmacol.
Hypothyroxinemia and hypothermia in rat in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin administration
Toxicol. Appl. Pharmacol.
Activity of thyroid hormone-inducible enzymes following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin
Toxicol. Appl. Pharmacol.
Blood serum levels of PCDFs and PCBs in Yu-Cheng children perinatally exposed to a toxic rice oil
Chemosphere
stm man C, Hagmar L. The impact of age, lactation and dietary habits on PCB in plasma in Swedish women
Sci. Total Environ.
Developmental neurotoxicity of PCBs in humans: what do we know and where do we go from here
Neurotoxicol. Teratol.
Neurotoxicity of environmental chemicals and their mechanism of action
Toxicol. Lett.
Enhanced thyroxine metabolism and high uptake goiters in rats after a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin
Endocrinology
Middle-ear disease in children exposed prenatally to polychlorinated biphenyls and polychlorinated dibenzofurans
Arch. Environ. Health
Systematic review of the evidence for the etiology of adult sudden sensorineural hearing loss
Laryngoscope
Cognitive development of Yu-Cheng (‘oil-disease’) children prenatally exposed to heat-degraded PCBs
J. Am. Med. Assoc.
Cited by (12)
Environmental ototoxicants, a potential new class of chemical stressors
2019, Environmental ResearchCitation Excerpt :Several of the chemical stressors with ototoxic properties that we have reviewed are ligands of the AhR. In fact, interaction with AhR has been assumed in the ototoxic effect of HCB (Hadjab et al., 2004) (see Section 3.2.2.1), gestational exposure to 2,3,4,7,8-penta-CDF (Li et al., 2015) and PCDD/Fs (Thömke et al., 2002) (see Section 3.3.). Oxygen is the most essential molecule for life.
Perinatal polychlorinated biphenyls and polychlorinated dibenzofurans exposure are associated with DNA methylation changes lasting to early adulthood: Findings from Yucheng second generation
2019, Environmental ResearchCitation Excerpt :To determine whether DNA methylation changes play a role in disease development, we conducted a prospective study to examine 1) whether there are DNA methylation changes in people perinatally exposed to high concentrations of PCBs and PCDFs, and 2) whether a dose-response relationship exists between epigenetic changes and perinatal PCB and PCDF exposure. Additional details of participant recruitment were described elsewhere (Chen et al., 1992a; Guo et al., 1994; Li et al., 2015b). In brief, Yucheng second generation was born between March 1979 and May 1989 to mothers exposed to PCBs and PCDFs (Chen et al., 1992b).
Hearing loss in children with e-waste lead and cadmium exposure
2018, Science of the Total EnvironmentCitation Excerpt :A previous epidemiological study reports that children living near a burned coal plant with a high concentration of arsenic present significantly higher pure-tone thresholds than non-exposed children for 0.125, 0.25, 0.5, and 1 kHz (Bencko and Symon, 1977). Children are at higher risk of having elevated hearing threshold at low frequencies in the right ear due to the gestational exposure to organic toxicants (Li et al., 2015). These results suggest that low frequency of hearing is more likely deterred by environmental toxicants.
DPOAEs in infants developmentally exposed to PCBs show two differently time spaced exposure sensitive windows
2016, ChemosphereCitation Excerpt :Among these health outcomes, hearing impairment was described in animals after exposure to PCBs (Crofton and Zoeller, 2005; Powers et al., 2006) and organohalogens as HCB (Hadjab et al., 2004), hexabromocyclododecane (Lilienthal et al., 2009) and polybrominated diphenyl ethers (Poon et al., 2011). Animal observations on ototoxicity of organochlorines have been extended to humans exposed to PCBs (Trnovec et al., 2008, 2010; Jusko et al., 2014; Min et al., 2014), organochlorine pesticides (Sisto et al., 2015) and furans (Li et al., 2015). Recently, the introduction of distortion product otoacoustic emission (DPOAE) measurements (Lasky et al., 2002) has helped increase the ability to detect potential ototoxicity, since the primary purpose of OAE tests is to determine cochlear status, specifically hair cell function.
Polychlorinated biphenyls in umbilical cord serum of newborns from Rio Grande do Sul state, Brazil
2015, Clinica Chimica ActaCitation Excerpt :Previous studies suggested that human exposure to PCBs is associated with the occurrence of various types of cancer, such as breast cancer [2–4], colon cancer [5], liver, stomach, intestinal and prostate cancers[6,7] and a recent study showed that poisoning due to PCBs and dioxins can affect quality of life 30 y after the exposure [8]. PCBs were also associated with the occurrence of miscarriages and premature births [9], with damage to the peripheral nervous system [10], with respiratory infections in children from birth to 5 y [11], with reduced immunity in children [12], with diabetes [13] and with asymmetric hearing loss [14]. PCB concentration in umbilical cord plasma is a good indicator of prenatal exposure to PCBs [15].