scholarly journals Immunotoxicity of Per- and Polyfluoroalkyl Substances: Insights into Short-Chain PFAS Exposure

Toxics ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 100
Author(s):  
Tracey Woodlief ◽  
Samuel Vance ◽  
Qing Hu ◽  
Jamie DeWitt
Keyword(s):  
Drinking Water ◽  
Nk Cell ◽  
Positive Control ◽  
Oral Exposure ◽  
Body Weights ◽  
Toxicological Data ◽  
Males And Females ◽  
Polyfluoroalkyl Substances ◽  
Compound Exposure ◽  
Control Terminal

Novel per- and polyfluoroalkyl substances (PFAS) were recently identified in drinking water sources throughout North Carolina. These include the perfluoroether acids (PFEAs) perfluoro-2-methoxyacetic acid (PFMOAA), perfluoro-2-methoxypropanoic acid (PFMOPrA), and perfluoro-4-methoxybutanioc acid (PFMOBA). Little toxicological data exist for these PFEAs. Therefore, the present study described signs of toxicity and immunotoxicity following oral exposure. Adult male and female C57BL/6 mice were exposed once/day for 30 days to PFMOAA (0, 0.00025, 0.025, or 2.5 mg/kg), PFMOPrA, or PFMOBA (0, 0.5, 5, or 50 mg/kg). A dose of 7.5 mg/kg of perfluorooctanoic acid (PFOA) was used as a positive control. Terminal body weights, and absolute liver, spleen, or thymus weights did not differ by dose for any compound; exposure to 50 mg/kg of PFMOBA increased relative liver weights in males. Changes in splenic cellularity were observed in males exposed to PFMOPrA and decreased numbers of B and natural killer (NK) cells were observed in males and females exposed to PFMOBA. Exposure did not alter NK cell cytotoxicity or T cell-dependent antibody responses at doses administered. Our results indicate that these “understudied” PFAS have toxicological potential but require additional investigation across endpoints and species, including humans, to understand health effects via drinking water exposure.

Immunotoxicity of an Electrochemically Fluorinated Aqueous Film-Forming Foam

2020 ◽  
Vol 178 (1) ◽  
pp. 104-114 ◽  
Author(s):  
Carrie A McDonough ◽  
Chastity Ward ◽  
Qing Hu ◽  
Samuel Vance ◽  
Christopher P Higgins ◽  
...  
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Perfluorooctane Sulfonate ◽  
Positive Control ◽  
Film Forming ◽  
Body Weights ◽  
Specific Antibody Production ◽  
Fire Suppressants ◽  
Contaminated Drinking Water ◽  
Induced Changes

Abstract Aqueous film-forming foams (AFFFs) are complex per- and polyfluoroalkyl substance (PFAS)-containing mixtures used extensively as fire suppressants. AFFF-impacted groundwater and surface water have contaminated drinking water with PFASs in many communities, raising concerns about health effects from drinking water exposures. As individual PFASs have been identified as immune hazards, the immunotoxicity of complex PFAS mixtures is also a concern. Adult female and male C57BL/6 mice were given a commercial AFFF formulation for 10 days via gavage; administered dose was based on combined content of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) measured in the formulation (0, 1.88, 3.75, 7.5, or 10 mg PFOS+PFOA/kg body weight). A PFOA positive control of 7.5 mg/kg body weight was also given. Compared with the 0 mg/kg group, the following changes were noted: Body weights of males exposed to 7.5 and 10 mg PFOS+PFOA/kg were reduced by 15%, on average; female body weights did not differ. Average relative liver weights were increased 50%–200% in males and 37.5%–193% in females and liver peroxisome proliferation was increased 2- to 12-fold in all doses of both sexes. Antigen-specific antibody production was suppressed, on average, by 13% in males and by 12.4% in females across all doses. Spleen cellularity and lymphocyte subpopulations did not differ by dose for either sex. Our data indicate that though this complex PFAS mixture contained fairly low PFOA content, it induced changes in C57BL/6 mice similar to changes induced by PFOA alone, likely due to the presence of PFOS and many other PFASs.

scholarly journals Historical Control Data of Spontaneous Tumors in Transgenic CByB6F1-Tg(HRAS)2Jic (Tg.rasH2) Mice

2013 ◽  
Vol 32 (1) ◽  
pp. 48-57 ◽  
Author(s):  
Madhav G. Paranjpe ◽  
Reem H. Elbekaei ◽  
Sudhir A. Shah ◽  
Michelle Hickman ◽  
Martin L. Wenk ◽  
...  
Keyword(s):  
Positive Control ◽  
Regulatory Agencies ◽  
High Survival ◽  
Spontaneous Tumors ◽  
Body Weights ◽  
Males And Females ◽  
Historical Database ◽  
Low Incidence ◽  
Historical Control Data ◽  
Very High

The Tg.rasH2 mouse is a hemizygous transgenic mouse, approved by regulatory agencies for carcinogenicity assessment. However, the absence of a historical database for the incidence of spontaneous neoplasms has subsequently led to reluctance by some pharmaceutical companies to adopt the use of this short-term carcinogenicity assay. Our laboratory has generated a database summarizing the mortality, body weights, and the incidence of spontaneous tumors in 1420 male and female mice assigned to 26 studies conducted at our facility. In addition, we present the incidence of tumors in positive control mice treated with urethane from these studies. Mortality in the vehicle-treated Tg.rasH2 mouse was low (average of 1% in each study). The most common spontaneous tumors in the Tg.rasH2 mice were alveolar bronchiolar adenoma of the lungs (10.14% in males and 5.77% in females) and hemangiosarcoma of the spleen (3.66% in both males and females). The incidence of all other tumors was generally very low. In the positive control, urethane-treated animals, the incidence of alveolar bronchiolar adenomas and alveolar bronchiolar carcinomas in the lungs was 93.69% and 42.88% in males and 92.43% and 72.79% in females, respectively. In addition, the incidence of splenic hemangiosarcomas in urethane-treated males was 89.18% and 92.25% in females. The 6-month Tg.rasH2 assay is more precise, faster, and more economical than the conventional 2-year mouse assays because of the low incidence of background tumors, very high survival, shorter duration, and the lower number of animals used.

scholarly journals Therapeutic effects of sesamolin on leukemia induced by WEHI-3B in model mice

2021 ◽  
Vol 64 (1) ◽  
Author(s):  
Senthil Nagarajan ◽  
Jae Kwon Lee
Keyword(s):  
Nk Cell ◽  
Neoplastic Cell ◽  
Positive Control ◽  
Cytolytic Activity ◽  
Leukemic Cells ◽  
Therapeutic Effects ◽  
Control Drug ◽  
Lysis Activity

AbstractSesamolin is one of the lignans derived from sesame oil. It has demonstrated significant antioxidant, anti-aging, and anti-mutagenic properties. It also reportedly augments natural killer (NK) cell lysis activity. We previously reported that sesamolin also exerts anticancer effects in vitro and induces enhanced NK cell cytolytic activity against tumor cells. Herein, we aimed to determine the mechanism by which sesamolin prevents and retards tumorigenesis in BALB/c mouse models of leukemia induced by murine (BALB/c) myelomonocytic leukemia WEHI-3B cells. Banded neutrophils, myeloblasts, and monocytic leukemic cells were more abundant in the leukemia model than in normal mice. Sesamolin decreased the number of leukemic cells by almost 60% in the leukemia model mice in vivo; additionally, sesamolin and the positive control drug, vinblastine, similarly hindered neoplastic cell proliferation. Spleen samples were ~ 4.5-fold heavier in leukemic mice than those obtained from normal mice, whereas spleen samples obtained from leukemic mice treated with sesamolin had a similar weight to those of normal mice. Moreover, sesamolin induced a twofold increase in the cytotoxic activity of leukemic mouse NK cells against WEHI-3B cells. These results indicated that sesamolin exerts anti-leukemic effects in vivo.

Male reproductive toxicity of sodium arsenite in mice

2004 ◽  
Vol 23 (8) ◽  
pp. 399-403 ◽  
Author(s):  
Niraj Pant ◽  
R C Murthy ◽  
S P Srivastava
Keyword(s):  
Drinking Water ◽  
Sodium Arsenite ◽  
Sperm Count ◽  
Prostate Gland ◽  
Reproductive Toxicity ◽  
Atomic Absorption Spectrophotometry ◽  
Reproductive Organs ◽  
Oral Exposure ◽  
Human Beings ◽  
Testicular Weight

The effect of chronic oral exposure to arsenic on male mouse testicular and accessory sex organ weights, sperm parameters and testicular marker enzymes was studied. In addition, the distribution of arsenic in reproductive organs was measured using atomic absorption spectrophotometry. Sodium arsenite administered to mice (Mus musculus) via drinking water at a dose of 53.39 βmol/L (4 ppm As) for 365 days caused a decrease in the absolute and relative testicular weight. However, epididymal and accessory sex organ weight was similar to control. The activities of marker testicular enzymes such as sorbitol dehydrogenase, acid phosphatase and 17β-hydroxysteroid dehydrogenase (17β-HSD) were significantly decreased, but those of lactate dehydrogenase and γ-glutamyl transpeptidase (γ-GT) were significantly increased. A decrease in sperm count and sperm motility, along with an increase in abnormal sperm, was observed in arsenite-exposed mice. A significant accumulation of arsenic in testes, epididymis, seminal vesicle and prostate gland was observed in treated animals. Thus long term exposure (365 days) at the dose level of 53.39 μmol/L sodium arsenite (4 ppm As), to which human beings are likely to be exposed via drinking water, may cause testicular and spermatotoxic effect.

Oral exposure to hexavalent chromium through drinking water and urologic morbidity in an industrial area of Greece

2015 ◽  
Vol 23 (5) ◽  
pp. 249-255 ◽  
Author(s):  
Dimitrios Karagiannis ◽  
Charalambos Deliveliotis ◽  
Eleni Papadimitriou ◽  
Elena Riza ◽  
Anastasia Lykou ◽  
...  
Keyword(s):  
Drinking Water ◽  
Hexavalent Chromium ◽  
Industrial Area ◽  
Oral Exposure ◽  
Of Greece

Oral (Drinking Water) Two-Generation Reproductive Toxicity Study of Bromodichloromethane (BDCM) in Rats

2002 ◽  
Vol 21 (2) ◽  
pp. 115-146 ◽  
Author(s):  
M. S. Christian ◽  
R. G. York ◽  
A. M. Hoberman ◽  
L. C. Fisher ◽  
W. Ray Brown
Keyword(s):  
Drinking Water ◽  
Reproductive Toxicity ◽  
Clinical Signs ◽  
Sperm Parameters ◽  
Feed Consumption ◽  
Exposure Level ◽  
Organ Weights ◽  
Reduced Body ◽  
Body Weights ◽  
Adult Exposure

Bromodichloromethane (BDCM) was tested for reproductive toxicity in a two-generation study in CRL SD rats. Thirty rats/sex/group/generation were continuously provided BDCM in drinking water at 0 (control carrier, reverse osmosis membrane-processed water), 50, 150, and 450 ppm (0,4.1 to 12.6, 11.6 to 40.2, and 29.5 to 109.0 mg/kg/day, respectively). Adult human intake approximates 0.8 μg/kg/day (0.0008 mg/kg/day). P and F1 rats were observed for general toxicity (viability, clinical signs, water and feed consumption, body weights, organ weights [also three weanling F1 and F2 pups/sex/litter], histopathology [10/sex, 0-and 450-ppm exposure groups]) and reproduction (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios, viabilities, maternal behaviors, reproductive organ weights [also three weanling F1 and F2 pups/sex/litter], sperm parameters, and implantations. F1 rats were evaluated for age at vaginal patency or preputial separation. Ten P and F1 rats/sex from the 0-and 450-ppm exposure groups and rats at 50 and 150 ppm with reduced fertility were evaluated for histopathology (gross lesions, testes, intact epididymis, all F1 dams for number of primordial follicles). Developmental parameters in offspring included implantation and pup numbers, sexes, viabilities, body weights, gross external alterations, and reproductive parameters (F1 adults). Toxicologically important, statistically significant effects at 150 and/or 450 ppm included mortality and clinical signs associated with reduced absolute and relative water consumption, reduced body weights and weight gains, and reduced absolute and relative feed consumption (P and F1 rats). Significantly reduced body weights at 150 and 450 ppm were associated with reduced organ weights and increased organ weight ratios (% body and/or brain weight). Histopathology did not identify abnormalities. Small delays in sexual maturation (preputial separation, vaginal patency) and more F1 rats with prolonged diestrus were also attributable to severely reduced pup body weights. Mating, fertility, sperm parameters, and primordial ovarian follicular counts were unaffected. The no-observable-adverse-effect level (NOAEL) and the reproductive and developmental NOAELs for BDCM were at least 50 ppm (4.1 to 12.6 mg/kg/day), 5125 to 15,750 times the human adult exposure level, if delayed sexual maturational associated with severely reduced body weights is considered reproductive toxicity. If considered general toxicity, reproductive and developmental NOAELs for BDCM are greater than 450 ppm (29.5 to 109.0 mg/kg/day), or 36,875 to 136,250 times the human adult exposure level. Regardless, these data indicate that BDCM should not be identified as a risk to human reproductive performance or development of human conceptuses.

scholarly journals Effectiveness of point‐of‐use/point‐of‐entry systems to remove per‐ and polyfluoroalkyl substances from drinking water

2019 ◽  
Vol 1 (2) ◽  
pp. e1131 ◽  
Author(s):  
Craig Patterson ◽  
Jonathan Burkhardt ◽  
Donald Schupp ◽  
E. Radha Krishnan ◽  
Stephen Dyment ◽  
...  
Keyword(s):  
Drinking Water ◽  
Point Of Entry ◽  
Point Of Use ◽  
Polyfluoroalkyl Substances

scholarly journals Suplementasi Sari Belimbing Wuluh (Averrhoa bilimbi L.) dalam Air Minum terhadap Produktivitas Telur Puyuh

2020 ◽  
Vol 18 (2) ◽  
pp. 54-61
Author(s):  
Lylya Wahyuni ◽  
M R Ramdani ◽  
N O Imama ◽  
V E Larasati ◽  
A R Fahmi ◽  
...  
Keyword(s):  
Drinking Water ◽  
Egg Quality ◽  
Egg Yolk ◽  
Positive Control ◽  
Feed Conversion ◽  
Physical Quality ◽  
Randomized Design ◽  
Egg Shells ◽  
Haugh Unit

Supplementation of Averrhoa bilimbi L. juice which contains vitamin C and organic acid in drinking water has been proposed to reduce the effect of heat stress on the quail layer.  So this is expected to increase the productivity of quail and their egg quality. The aim of this research was to determine the effect of A. bilimbi juice supplementation in quail drinking water on quail performance,  physical quality of egg, and egg yolk antioxidant level. Two hundred and forty birds aged 4-5 weeks were maintained for 42 days. A Completely Randomized Design was used in this study with 4 treatments. Each treatment has 4 replications and 15 quails in each replications. Addition of Vita Chick (P0) to the drinking water was used as a positive control. The treatments given were the addition of A. bilimbi extract with different levels of 0% (P1), 2.5% (P2), and  5% (P3) respectively. The variables observed were quail performance, physical egg quality, and egg yolk antioxidant levels. The results showed that the  physical quality of quail eggs obtained were the weight of albumen and egg shells did not different all treatments. The  addition of A. bilimbi juice in drinking water  has affected on the weight and percentage of albumen, eggshell, and Haugh Unit. The addition of 2.5% of A.bilimbi juice (P2)  had the lowest feed conversion ratio (FCR). However it showed the highest Haugh Unit number of the egg. There was no different effect of the highest dose of A. bilimbi juice (5%, P3) on the egg yolk antioxidant  activity and capacity (41.54%  and 23.91 ppm respectively).  It was concluded that supplementation of A. bilimbi juice in drinker water  could  changed to antistress drug commercial.

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