Testicular spermiation failure in rats exposed prenatally to 3,3',4,4',5-pentachlorobiphenyl

Wakui, Shin; Muto, Takayoshi; Motohashi, Masaya; Kobayashi, Yasuko; Suzuki, Yoshihiko; Takahashi, Hiroyuki; Hano, Hiroshi

doi:10.2131/jts.35.757

Cited by 8 publications

(12 citation statements)

References 59 publications

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“…Regarding DL‐PCBs, and contrary to experimental animals (e.g. Wakui et al., , see Annex A.5), there is no conclusive evidence based on humans studies. The CONTAM Panel noted the uncertainty in relation to the association with PCDF exposure, but other studies on semen quality in relation to high PCDF exposure, e.g.…”

Section: Assessmentmentioning

confidence: 95%

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

Knutsen¹,

Alexander²,

Barregård³

et al. 2018

EFS2

143

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The European Commission asked EFSA for a scientific opinion on the risks for animal and human health related to the presence of dioxins (PCDD/Fs) and DL‐PCBs in feed and food. The data from experimental animal and epidemiological studies were reviewed and it was decided to base the human risk assessment on effects observed in humans and to use animal data as supportive evidence. The critical effect was on semen quality, following pre‐ and postnatal exposure. The critical study showed a NOAEL of 7.0 pg WHO2005‐TEQ/g fat in blood sampled at age 9 years based on PCDD/F‐TEQs. No association was observed when including DL‐PCB‐TEQs. Using toxicokinetic modelling and taking into account the exposure from breastfeeding and a twofold higher intake during childhood, it was estimated that daily exposure in adolescents and adults should be below 0.25 pg TEQ/kg bw/day. The CONTAM Panel established a TWI of 2 pg TEQ/kg bw/week. With occurrence and consumption data from European countries, the mean and P95 intake of total TEQ by Adolescents, Adults, Elderly and Very Elderly varied between, respectively, 2.1 to 10.5, and 5.3 to 30.4 pg TEQ/kg bw/week, implying a considerable exceedance of the TWI. Toddlers and Other Children showed a higher exposure than older age groups, but this was accounted for when deriving the TWI. Exposure to PCDD/F‐TEQ only was on average 2.4‐ and 2.7‐fold lower for mean and P95 exposure than for total TEQ. PCDD/Fs and DL‐PCBs are transferred to milk and eggs, and accumulate in fatty tissues and liver. Transfer rates and bioconcentration factors were identified for various species. The CONTAM Panel was not able to identify reference values in most farm and companion animals with the exception of NOAELs for mink, chicken and some fish species. The estimated exposure from feed for these species does not imply a risk.

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Section: Assessmentmentioning

confidence: 95%

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

Knutsen¹,

Alexander²,

Barregård³

et al. 2018

EFS2

143

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“…PCB exposure studies have demonstrated conflicting relationships with male hormones in both animal (Wakui et al 2010; Xiao et al 2011; Xu et al 2013; Zhu et al 2013) and human studies. For example, in a cohort of boys with higher prenatal exposure to PCBs during the Yucheng incident in 1978–79 (n=47) and unexposed controls (n=49), exposed boys who were at puberty (≥13 years old) had lower T levels and higher estradiol and FSH levels (non-significant) compared to controls, but there was no difference in boys < 13 years; there were also no differences in LH levels (Hsu et al 2005).…”

Section: Introductionmentioning

confidence: 99%

In utero and childhood DDT, DDE, PBDE and PCBs exposure and sex hormones in adolescent boys: The CHAMACOS study

Eskenazi

Rauch

Tenerelli

et al. 2017

International Journal of Hygiene and Environmental Health

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Dichlorodiphenyltrichloroethane (DDT), polybrominated diphenyl ether (PBDE) flame retardants, and polychlorinated biphenyls (PCBs) are believed to be endocrine-disrupting chemicals (EDCs) in humans and animals. The purpose of this study is to examine the relationship of in utero and childhood exposure to these purported EDCs and reproductive hormones in adolescent boys who participated in CHAMACOS, an ongoing birth cohort in California’s Salinas Valley. We measured o,p′- and p,p′-DDT, p,p′- DDE, PBDEs and PCBs in serum collected from mothers during pregnancy or at delivery and from their sons at 9 years. We measured concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone (T) from 234 of their sons at 12 years. In adjusted models, we found that a 10-fold increase in maternal prenatal serum concentrations of BDE-153 was associated with a 22.2% increase (95% CI: 1.0, 47.9) in FSH, a 96.6% increase (95% CI: 35.7, 184.7) in LH, and a 92.4% increase (95% CI: 20.9, 206.2) increase in T. Similarly, BDE-100 concentrations were associated with increases in boys’ LH levels. A 10-fold increase in total prenatal ΣPCBs was associated with a 64.5% increase (95% CI: 8.6, 149.0) in FSH, primarily driven by non-dioxin-like congeners. Boys’ hormone levels were only marginally associated with prenatal DDT or DDE in primary models, but when boys’ Tanner stage at age 12 was added to models, prenatal maternal DDT levels were associated with decreases in LH (adjusted percent change per 10-fold increase = −18.5%, 95% CI: −29.8, −5.4) and T (percent change = −18.2%, 95% CI: −30.2, −4.2) and DDE with LH (percent change = −18.3%, 95% CI: −32.9, −0.6). Exposures measured in the children’s serum at 9 years also showed associations between BDE-153 and ΣPCBs. However, there is evidence that these associations appear to be mediated by child BMI. This study suggests associations on male hormones of 12 year old boys related to exposure to certain EDC exposure prenatally. The implications on future reproductive function in puberty and adulthood should be determined.

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“…The studies were conducted in rats, mice or goats. We identified four studies examining the effects of PCB-77 [ 39 – 42 ], two studies on those of PCB-118 [ 43 , 44 ], four studies which looked at PCB-126 [ 39 , 45 – 47 ], two studies for PCB-132 [ 48 , 49 ], one study for PCB-149 [ 48 ], two studies reporting on PCB-153 [ 45 , 50 ], two on PCB-169 [ 51 , 52 ] and one report on PCB-180 [ 53 ]. All these studies were selected for the data extraction process.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…There were four studies of PCB-126, of which one was conducted in goats [ 45 ] and the other three in rats [ 39 , 46 , 47 ]. The goat study and two of the rat studies were rated at an overall confidence level of “ High ” ( TIER 1 ) due to all elements being evaluated as “definitely low” or “probably low risk” [ 45 – 47 ]. The third rat study was evaluated as “definitely low” or “probably low risk” in the key elements but had some other elements rated lower and was thus assigned to TIER 2 , Medium confidence [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

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Systematic review of associations of polychlorinated biphenyl (PCB) exposure with declining semen quality in support of the derivation of reference doses for mixture risk assessments

Ermler

Kortenkamp

2022

Environ Health

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Background Mixture risk assessments require reference doses for common health endpoints of all the chemicals to be considered together. In support of a mixture risk assessment for male reproductive health, we conducted a systematic review of the literature on associations between exposures to Polychlorinated Biphenyls (PCBs) and declines in semen quality. PCBs can act as Aryl-hydrocarbon Receptor (AhR)-agonists and Androgen Receptor (AR)-antagonists, both mechanisms which can affect sperm parameters. PCBs and other AR-antagonists can produce additive combination effects. Based on these observations our objective was to systematically gather data from animal and human studies to derive a reference dose for declines in semen quality for individual PCB. Methods We systematically reviewed and evaluated the evidence in human epidemiological and experimental animal studies on associations between PCBs and deteriorations in semen quality. Human data and findings from animal studies with PCB mixtures were considered as supporting evidence. Information for individual congeners from animal studies was required for inclusion in mixture risk assessment. Using a robust confidence rating approach, we identified suitable studies to derive reference doses for individual PCB congeners. Results Evaluation of human epidemiological studies revealed several reports of adverse effects on sperm parameters linked to PCB exposures, although some studies reported improved semen quality. Our review of experimental animal studies found that treatments with PCBs affected semen quality, in most cases adversely. We found robust evidence that PCB-118 and -169 were linked to declines in semen quality. Evidence for adverse effects of PCB-126, -132, -149, and -153 was moderate, whereas for PCB-77 it was slight and for PCB-180 indeterminate. Using widely accepted risk assessment procedures, we estimated reference dose values of 0.0029 µg/kg/day for PCB-118 and 0.00533 µg/kg/day for PCB-169. In addition, we derived values for PCB-126: 0.000073 µg/kg/day, PCB-132: 0.0228 µg/kg/day, PCB-149: 0.656 µg/kg/day, and PCB-153: 0.0058 µg/kg/day. Conclusions We found robust evidence for links between PCB exposure and deteriorations in semen quality, and derived reference doses for a set of congeners. We intend to use these values in combination with congener-specific exposure data in a mixture risk assessment for declines in semen quality, involving several other antiandrogenic chemicals.

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Testicular spermiation failure in rats exposed prenatally to 3,3',4,4',5-pentachlorobiphenyl

Cited by 8 publications

References 59 publications

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

In utero and childhood DDT, DDE, PBDE and PCBs exposure and sex hormones in adolescent boys: The CHAMACOS study

Systematic review of associations of polychlorinated biphenyl (PCB) exposure with declining semen quality in support of the derivation of reference doses for mixture risk assessments

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