Effects of Polychlorinated Biphenyl (PCB)

Effects of Polychlorinated Biphenyl (PCB) Polychlorinated Biphenyl (PCB) is a persistent organochlorine that has 209 congeners and can be divided into two categories, dioxin-like and non-dioxin-like. Although these two categories have different structures and toxicological profiles, both have an adverse impact on the human health [1]. Since PCB is a stable chemical and can withstand extreme temperature and pressure, it was heavily used back in 1929 for electrical equipment [2]. While the production of PCB was ceased in 1977, traces of PCB can still be observed on the Great Lakes for it was once used as a disposal site along with the possibility of accidental leaks. From lakes, it can move into different waterways and later be passed on by organisms. Long-range-transport of PCB vapours through air currents also functions as a dispersion mechanism in the ambient air [3] [4] [5]. Anyone can be susceptible depending on the rate of the exposure and the amount of stressor a person had been exposed to. PCB can enter the system thro ugh ingestion, inhalation and dermal contact, all of which can essentially bioaccumulate and inhibit the bodys natural processes in the event that the receptor had exceeded the threshold. PCB has been linked to endocrine dysfunction, reproduction deficiencies, chloracne, liver damage and kidney cancer [6]. Recognizing credible sources is a key factor in toxicity assessment. This allows the reader to acquire more information about the chemical of concern and make an informed decision. Some credible sources are listed below: Agency for Toxic Substances and Disease Registry European Chemicals Agency Health Canada United States Environmental Protection Agency World Health Organization     Ã‚   3.1. What happens when PCB enters the body? Humans absorb PCB through inhalation, ingestion and dermal contact. On bioassays conducted, it was observed that animals absorbed PCB well when administered orally and less absorbed when exposed through dermal contact. While inhalation is an accounted pathway for PCB, there is inadequate data to identify the absorption rates. Upon absorption, PCB is dispersed into the lipophilic cell membranes in the gastrointestinal tract. It then circulates into the blood vessels and enters the lymphatic system. Due to the lipophilic nature of PCB molecules, it is readily absorbed by the fatty tissue. In autopsies conducted, the liver, adipose tissue, brain and skin usually contains higher concentrations of PCB. Elimination of PCB can be through excretion of feces, urine and breast milk [7]. When exposed to PCB, symptoms include severe acne, swelling of the upper eyelids, discolouring of the nails and skin, numbness in arms and/or legs, weakness, muscle spasms, chronic bronchitis, and neurological complications [6]. 3.2. Acute and Chronic Effects PCB exhibits both acute and chronic effects. Although it demonstrates low potential in producing acute effects, however, due to the risk it poses in human health in the long-term, it is still deemed to be a public health concern. Skin lesions particularly chloracne has been observed during occupational exposures. Nausea and headaches were also reported yet this could be primarily due to the solvents in the PCB mixtures. Subsequently, long-term exposure to PCB has been linked to reproductive deficiencies, liver damage and kidney cancer [8]. 3.3. Threshold vs Non-threshold PCB has shown evident carcinogenicity in animals and therefore is considered to be non-threshold substance by USEPA. The data for human carcinogenicity for PCB mixture is deemed to be inadequate but suggestive. Essentially, PCB can also be classified as threshold substance because of its non-cancer potential in lower concentrations and short-term exposure [9].   3.4. What effects does it have? Carcinogenic US EPA labeled PCB as Group B2, a probable human carcinogen. This was based on the experiment of exposure of rats to several mixtures of PCB that are often found in the environment [10]. On a study published in 1976, occupational exposure to PCB increased the mortality from cancer. However, the outcomes were mixed since the study only found limited deaths and incomplete exposure assessments [7]. Mutagenicity There were insufficient data involving the mutagenicity of PCB [7]. A bacterial test which distinguishes chemical mutation effects was conducted on PCB. Although PCB demonstrated negative results, this was not uncommon since PCB has complex compounds and pathways [11]. Reproductive Toxicity Oral administration of PCB on animals has displayed toxicity effects but dermal and inhalation exposure were not available. Exposure of rats and mice to high doses of PCB had produced several effects. The effects documented were decreased conception rate, pro-longed menstruation, decreased litter size and reduced sperm count. Rats and mice that were exposed to PCB while lactation suggested long-lasting adverse effect on the offspring. On another study, PCB is also associated to estrogen-related effects [7]. 4.1. Bioassay Overview The slope factor of PCB was based upon the studies conducted by Brunner et al. (1996) and Norback and Weltman (1985). A group of male and female Sprague-Dawley rats were exposed to different Aroclor. Groups of 50 female or male rats were orally administered with 25, 50 or 100 ppm Aroclor 1260 or 1254; 50 or 100 ppm Arcolor 1242; or 50, 100, or 200 ppm Aroclor 1016. At 104 weeks, the rats were killed. Liver adenomas or carcinomas were discovered in all female rats for all Aroclors and male rats for Aroclor 1260. While thyroid gland follicular cell carcinoma was evident on male rats, female rats also exhibited mammary tumors at a later age. On another study, male and female Sprague-Dawley rats were exposed to 0 or 100ppm of Aroclor 1260 for 16 months and subsequently reduced to 50 ppm for another 8 months. Tests were executed in different months to understand the changes in the structure of the rats. The intensity of the damage on the liver increases as you progress through the months. On the 29th month, most of the female rats displayed carcinoma and neoplastic nodules whereas male rats had lesser incidence [10] . 4.2. Published Benchmark A tiered approach was used by USEPA to determine the cancer potency of PCB. Upper-bounds provide precision while central-estimates are appropriate for estimating risks. Potency values are dependent on the exposure pathway. For exposure pathways with increased risks, we use High Risk and Persistence. Exposure pathways that decrease risk are appropriate on Low Risk and Persistence. Lowest Risk and Persistence is developed from Aroclor 2016, therefore it is appropriate for congeners with more than for chlorine. The slope factor can be generated by dividing 0.10 by ED10 (Estimated dose associated with 10% increased incidence, in mg/kg-d) [12]. High Risk and Persistence Low Risk and Persistence Lowest Risk and Persistence Upper-Bound Slope Factor 2.0 per (mg/kg)/day 0.4 per (mg/kg)/day 0.07 per (mg/kg)/day Central-Estimate Slope Factor 1.0 per (mg/kg)/day 0.3 per (mg/kg)/day 0.04 per (mg/kg)/day Criteria for use Food chain exposure Sediment or soil ingestion Dust or aerosol inhalation Dermal exposure, if an absorption factor has been applied Presence of dioxin-like, tumor-promoting, or persistent congeners Early-life exposure (all pathways and mixtures) Ingestion of water-soluble congeners Inhalation of evaporated congeners Dermal exposure, if no absorption factor has been applied Congener or isomer analyses verify that congeners with more than 4 chlorines comprise less than 1/2% of total PCBs. Figure 1 Tiers of Human Slope Factors For Environmental PCB [13]. Uncertainty Factors It is important to know that not everyone responds equally to a given chemical. Populations with higher sensitivity may be associated with increased risks. Also, the genetics and lifestyle of a person must be accounted as this pose potential change on the dose-response trend. Furthermore, it is essential to recognize that the mixtures of PCB tested in animals are Aroclor mixtures which have been pre-determined and not environmental mixtures that had bioaccumulated which are generally more potent [10]. Figure 1 shows that the slope factor is dependent upon the exposure pathway. Although these are just estimates, scientists have dedicated their time to conduct bioassays where we can extrapolate the data to potentially understand the dose that can harm humans. However, it is also crucial to know that environmental processes can alter the PCB concentrations, therefore it is best to be educated on how you can be exposed to PCB and how you can avoid this. To improve the assessment, studies concerning sensitive population should be further considered and assessed. Since PCB concentrations are altered in the environment, animals or humans that are already exposed could be used to investigate and compare the differences with the experiments done in the laboratory. In addition, it was not mentioned why rats were chosen as experiment parameters, analyzing parameters used could help readers discern why rats are relevant for the study. [1] P. Heikkinen, . L. T. M. van der Ven,, F. Rendel, R. Roos, J. Esteban, M. Korkalainen, S. Lensu, H. Miettinen, K. Savolainen, S. Sankari, H. Lilienthal, A. Adamsson, J. Toppari, M. Herlin, M. Finnila, J. Tukkanen, H. Leslie, T. Hammmers and G. Hamscher, Toxicological Profile of Ultrapure 2,2à ¢Ã¢â€š ¬Ã‚ ²,3,4,4à ¢Ã¢â€š ¬Ã‚ ²,5,5à ¢Ã¢â€š ¬Ã‚ ²-Heptachlorbiphenyl (PCB 180) in Adult Rats., PLoS ONE, vol. 9, no. 8, pp. 1-26, 2014. [2] PCBs: Polychlorinated Biphenyls, [Online]. Available: http://www.greenfacts.org/en/pcbs. [Accessed 2 February 2017]. [3] S. Fields, Great Lakes Resources at Risk, Environmental Health Perspectives, vol. 113, no. 3, pp. 164-173, 2005. [4] PCBs in Great Lakes Sediments, [Online]. Available: http://www.greatlakesmapping.org/great_lake_stressors/1/pcbs-great-lakes-sediments. [Accessed 1 February 2017]. [5] Polychlorinated Biphenyls (PCBs) Toxicity, 14 May 2014. [Online]. Available: https://www.atsdr.cdc.gov/csem/pcb/docs/pcb.pdf. [Accessed 02 February 2017]. [6] H. Canada, Health Canada, [Online]. Available: http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/environ/pcb-bpc-eng.php#ba. [Accessed 20 February 2017]. [7] M. L. S. K. M. C. S. D. C. T. D. R. Dr Obaid M. Faroon, World Health Organization, 2003. [Online]. Available: http://www.who.int/ipcs/publications/cicad/en/cicad55.pdf. [Accessed 13 February 2017]. [8] G. Letz, The Toxicology of PCBs-An Overview for Clinicians, West Journal of Medicine, pp. 536-538, 1983. [9] United States Environmental Protection Agency, [Online]. Available: https://www3.epa.gov/region02/superfund/hudson/hhra-app-c.pdf. [Accessed 20 February 2017]. [10] United States Environmental Protection Agency, 1 October 1996. [Online]. Available: https://cfpub.epa.gov/ncea/iris2/chemicalLanding.cfm?substance_nmbr=294. [Accessed 21 February 2017]. [11] Polychlorinated Biphenyls and Polybrominated Biphenyls., in IARC Monographs, IARC, 2016. [12] U. S. E. P. Agency, PCBs: Cancer Dose-Response Assessment and Application to Environmental Mixtures, September 1996. [Online]. Available: https://cfpub.epa.gov/ncea/iris_drafts/recordisplay.cfm?deid=12486. [Accessed 21 February 2017]. [13] United States Environmental Protection Agency, 1 June 1994. [Online]. Available: https://cfpub.epa.gov/ncea/iris2/chemicalLanding.cfm?substance_nmbr=294. [Accessed 21 February 2017].