Perfluorohexane Sulfonate (PFHxS) and a Mixture of Endocrine Disrupters Reduce Thyroxine Levels and Cause Antiandrogenic Effects in Rats

Louise Ramhøj, Ulla Hass, Julie Boberg, Martin Scholze, Sofie Christiansen, Flemming Nielsen, Marta Axelstad

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Resumé

The developmental toxicity of perfluorohexane sulfonate (PFHxS) is largely unknown despite widespread environmental contamination and presence in human serum, tissues and milk. To thoroughly investigate PFHxS toxicity in developing rats and to mimic a realistic human exposure situation, we examined a low dose close to human relevant PFHxS exposure, and combined the dose-response studies of PFHxS with a fixed dose of 12 environmentally relevant endocrine disrupting chemicals (EDmix). Two reproductive toxicity studies in time-mated Wistar rats exposed throughout gestation and lactation were performed. Study 1 included control, two doses of PFHxS, and two doses of PFHxS + EDmix (n = 5-7). Study 2 included control, 0.05, 5, or 25 mg/kg body weight/day PFHxS, EDmix-only, 0.05, 5, or 25 mg PFHxS/kg plus EDmix (n = 13-20). PFHxS caused no overt toxicity in dams and offspring but decreased male pup birth weight and slightly increased liver weights at high doses and in combination with the EDmix. A marked effect on T4 levels was seen in both dams and offspring, with significant reductions from 5 mg/kg/day. The EDmix caused antiandrogenic effects in male offspring, manifested as slight decreases in anogenital distance, increased nipple retention and reductions of the weight of epididymides, ventral prostrate, and vesicular seminalis. PFHxS can induce developmental toxicity and in addition results of the co-exposure studies indicated that PFHxS and the EDmix potentiate the effect of each other on various endpoints, despite their different modes of action. Hence, risk assessment may underestimate toxicity when mixture toxicity and background exposures are not taken into account.

OriginalsprogEngelsk
TidsskriftToxicological Sciences
Vol/bind163
Udgave nummer2
Sider (fra-til)579-591
ISSN1096-6080
DOI
StatusUdgivet - 1. jun. 2018

Fingeraftryk

Endocrine disrupters
Thyroxine
Rats
Toxicity
Dams
perflexane
Endocrine Disruptors
Nipples
Epididymis
Liver
Risk assessment

Citer dette

Ramhøj, Louise ; Hass, Ulla ; Boberg, Julie ; Scholze, Martin ; Christiansen, Sofie ; Nielsen, Flemming ; Axelstad, Marta. / Perfluorohexane Sulfonate (PFHxS) and a Mixture of Endocrine Disrupters Reduce Thyroxine Levels and Cause Antiandrogenic Effects in Rats. I: Toxicological Sciences. 2018 ; Bind 163, Nr. 2. s. 579-591.
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abstract = "The developmental toxicity of perfluorohexane sulfonate (PFHxS) is largely unknown despite widespread environmental contamination and presence in human serum, tissues and milk. To thoroughly investigate PFHxS toxicity in developing rats and to mimic a realistic human exposure situation, we examined a low dose close to human relevant PFHxS exposure, and combined the dose-response studies of PFHxS with a fixed dose of 12 environmentally relevant endocrine disrupting chemicals (EDmix). Two reproductive toxicity studies in time-mated Wistar rats exposed throughout gestation and lactation were performed. Study 1 included control, two doses of PFHxS, and two doses of PFHxS + EDmix (n = 5-7). Study 2 included control, 0.05, 5, or 25 mg/kg body weight/day PFHxS, EDmix-only, 0.05, 5, or 25 mg PFHxS/kg plus EDmix (n = 13-20). PFHxS caused no overt toxicity in dams and offspring but decreased male pup birth weight and slightly increased liver weights at high doses and in combination with the EDmix. A marked effect on T4 levels was seen in both dams and offspring, with significant reductions from 5 mg/kg/day. The EDmix caused antiandrogenic effects in male offspring, manifested as slight decreases in anogenital distance, increased nipple retention and reductions of the weight of epididymides, ventral prostrate, and vesicular seminalis. PFHxS can induce developmental toxicity and in addition results of the co-exposure studies indicated that PFHxS and the EDmix potentiate the effect of each other on various endpoints, despite their different modes of action. Hence, risk assessment may underestimate toxicity when mixture toxicity and background exposures are not taken into account.",
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year = "2018",
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Perfluorohexane Sulfonate (PFHxS) and a Mixture of Endocrine Disrupters Reduce Thyroxine Levels and Cause Antiandrogenic Effects in Rats. / Ramhøj, Louise; Hass, Ulla; Boberg, Julie; Scholze, Martin; Christiansen, Sofie; Nielsen, Flemming; Axelstad, Marta.

I: Toxicological Sciences, Bind 163, Nr. 2, 01.06.2018, s. 579-591.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Perfluorohexane Sulfonate (PFHxS) and a Mixture of Endocrine Disrupters Reduce Thyroxine Levels and Cause Antiandrogenic Effects in Rats

AU - Ramhøj, Louise

AU - Hass, Ulla

AU - Boberg, Julie

AU - Scholze, Martin

AU - Christiansen, Sofie

AU - Nielsen, Flemming

AU - Axelstad, Marta

PY - 2018/6/1

Y1 - 2018/6/1

N2 - The developmental toxicity of perfluorohexane sulfonate (PFHxS) is largely unknown despite widespread environmental contamination and presence in human serum, tissues and milk. To thoroughly investigate PFHxS toxicity in developing rats and to mimic a realistic human exposure situation, we examined a low dose close to human relevant PFHxS exposure, and combined the dose-response studies of PFHxS with a fixed dose of 12 environmentally relevant endocrine disrupting chemicals (EDmix). Two reproductive toxicity studies in time-mated Wistar rats exposed throughout gestation and lactation were performed. Study 1 included control, two doses of PFHxS, and two doses of PFHxS + EDmix (n = 5-7). Study 2 included control, 0.05, 5, or 25 mg/kg body weight/day PFHxS, EDmix-only, 0.05, 5, or 25 mg PFHxS/kg plus EDmix (n = 13-20). PFHxS caused no overt toxicity in dams and offspring but decreased male pup birth weight and slightly increased liver weights at high doses and in combination with the EDmix. A marked effect on T4 levels was seen in both dams and offspring, with significant reductions from 5 mg/kg/day. The EDmix caused antiandrogenic effects in male offspring, manifested as slight decreases in anogenital distance, increased nipple retention and reductions of the weight of epididymides, ventral prostrate, and vesicular seminalis. PFHxS can induce developmental toxicity and in addition results of the co-exposure studies indicated that PFHxS and the EDmix potentiate the effect of each other on various endpoints, despite their different modes of action. Hence, risk assessment may underestimate toxicity when mixture toxicity and background exposures are not taken into account.

AB - The developmental toxicity of perfluorohexane sulfonate (PFHxS) is largely unknown despite widespread environmental contamination and presence in human serum, tissues and milk. To thoroughly investigate PFHxS toxicity in developing rats and to mimic a realistic human exposure situation, we examined a low dose close to human relevant PFHxS exposure, and combined the dose-response studies of PFHxS with a fixed dose of 12 environmentally relevant endocrine disrupting chemicals (EDmix). Two reproductive toxicity studies in time-mated Wistar rats exposed throughout gestation and lactation were performed. Study 1 included control, two doses of PFHxS, and two doses of PFHxS + EDmix (n = 5-7). Study 2 included control, 0.05, 5, or 25 mg/kg body weight/day PFHxS, EDmix-only, 0.05, 5, or 25 mg PFHxS/kg plus EDmix (n = 13-20). PFHxS caused no overt toxicity in dams and offspring but decreased male pup birth weight and slightly increased liver weights at high doses and in combination with the EDmix. A marked effect on T4 levels was seen in both dams and offspring, with significant reductions from 5 mg/kg/day. The EDmix caused antiandrogenic effects in male offspring, manifested as slight decreases in anogenital distance, increased nipple retention and reductions of the weight of epididymides, ventral prostrate, and vesicular seminalis. PFHxS can induce developmental toxicity and in addition results of the co-exposure studies indicated that PFHxS and the EDmix potentiate the effect of each other on various endpoints, despite their different modes of action. Hence, risk assessment may underestimate toxicity when mixture toxicity and background exposures are not taken into account.

U2 - 10.1093/toxsci/kfy055

DO - 10.1093/toxsci/kfy055

M3 - Journal article

C2 - 29518214

VL - 163

SP - 579

EP - 591

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 2

ER -