Absorption, Distribution and Excretion
Specific information regarding the oral absorption of Aroclor 1254 is limited. Following a single oral ingestion of Aroclor 1254 (approximately 0.06 mg/kg) in pregnant ferrets, approximately 85% of the initial dose was absorbed. Studies primarily targeting single chlorinated biphenyl homologues have shown that polychlorinated biphenyls (PCBs) are generally readily and extensively absorbed in animals. These studies found oral absorption efficiencies of over 75% to 90% in rats, mice, and monkeys. Studies of non-Aroclor 54% chlorinated PCB mixtures prepared by researchers provide direct evidence of PCB absorption following oral exposure in humans, while studies of the general population consuming contaminated fish provide indirect evidence of PCB absorption via oral inhalation. Quantitative data on the absorption of inhaled PCBs in humans are currently unavailable, but studies on workers exposed to PCBs indicate that they are readily absorbed via inhalation and dermal routes. PCBs preferentially distribute in adipose tissue and are enriched in breast milk due to its high fat content. When pheasants were fed Aroclor 1254 at a single 50 mg dose or weekly doses of 12.5 mg or 50 mg for 17 consecutive weeks, up to 82% of Aroclor 1254 was absorbed into the gastrointestinal tract, and PCBs up to 50 mg/kg (wet weight) were detected in their eggs. Sherman rats fed Aroclor 1254 daily at doses of 10 or 50 mg/kg body weight on days 7–15 of gestation had mean PCB concentrations of 0.63 and 1.38 mg/kg in fetuses delivered by cesarean section on day 20 of gestation, respectively, compared to less than 0.12 mg/kg in the control group. In dairy cows fed 200 mg Aroclor 1254 daily for 60 consecutive days, the mean concentration in milk fat was 60 mg/kg (measured between days 40 and 60 of feeding). For more complete data on the absorption, distribution, and excretion of Aroclor 1254 (out of 19), please visit the HSDB records page. Metabolism/Metabolites The metabolism of polychlorinated biphenyls (PCBs) in laboratory animals has been extensively studied. Many substrates have been tested, and PCBs are typically administered orally or parenterally. In general, these studies suggest that the metabolic rate of PCBs depends on the number and position of chlorine atoms on the benzene ring and the animal species. In rats, the elimination half-life of the four PCBs containing one, two, five, or six chlorine atoms increases with increasing chlorine number. The excretion rate decreases with increasing chlorination, which is directly related to the decreased metabolic rate of highly chlorinated homologues. Sheep liver microsomes convert 2,2',5-trichlorobiphenyl to at least five more polar metabolites within 1 minute and to at least ten metabolites within 15 minutes; however, among homologues, 2,2',5,5'-tetrachlorobiphenyl and 2,2',4,5,5'-pentachlorobiphenyl are oxidized to only three metabolites, with conversion rates 7-fold and 14-fold slower, respectively. The number of chlorine atoms not only affects the biotransformation rate, but their position on the benzene ring is also crucial. This was confirmed in rats, where the rate of excretion of the four symmetrical hexachlorobiphenyls depended on the position of the chlorine atom. The percentage of drug excretion increased with increasing numbers of unsubstituted meta- or adjacent unsubstituted carbon atoms. Following gavage administration of 25 mg/kg Aroclor 1254 dissolved in peanut oil to rats, the predominant hydroxylated polychlorinated biphenyl metabolite in plasma was 4-hydroxy-2,3,3',4',5-pentachlorobenzene. From 1 to 14 days post-exposure, the concentration of this metabolite was 7–10 times higher than that of the main polychlorinated biphenyl (PCB) 153. The metabolism of PCBs after oral and parenteral administration in animals has been extensively studied and reviewed, but studies after inhalation or dermal exposure in animals are lacking. Information on PCB metabolism in humans is limited to occupationally exposed populations whose intake primarily comes from inhalation and dermal exposure. Generally, PCB metabolism depends on the number and position of chlorine atoms on the benzene ring of the constituent homologues (i.e., the homologue composition of a PCB mixture) and the animal species. Although data on the metabolism of PCBs after inhalation exposure are currently limited, there is no reason to doubt that PCBs are metabolized via this pathway differently from other pathways. Data are available on the in vitro hepatic metabolism and in vivo metabolic clearance of 2,2',3,3',6,6'-hexachlorobiphenyl and 4,4'-dichlorobiphenyl homologues in humans, monkeys, dogs, and rats. Hexachlorobiphenyl homologues are one of the components of Aroclor 1254. For each homologue, the Vmax values for in vivo metabolism in monkeys, dogs, and rats were consistent with the corresponding in vivo metabolic clearance values. Therefore, the PCB metabolic kinetic constants obtained from dog, monkey, and rat liver microsomal preparations can well predict the in vivo metabolism and clearance of these homologues. In a study aimed at determining which species could most accurately predict the metabolism and distribution of PCBs in humans, researchers also used human liver microsomes to study the in vitro metabolism of these homologues. Existing data indicate that the metabolism of polychlorinated biphenyls (PCBs) in humans is most similar to that in monkeys and rats. For example, the apparent Km and Vmax in vitro are comparable between humans and monkeys. These studies demonstrate consistency between in vitro and in vivo results and collectively indicate that the metabolism of these two homologues is similar in monkeys and humans. …To investigate the possible role of non-parenchymal cells in xenobiotic metabolism, we prepared non-parenchymal and parenchymal cell (PC) populations from mice and tested the activities of various xenobiotic metabolic enzymes. The specific activities of each enzyme studied (ethoxyhalothrin deethylase, amphetamine demethylase, glutathione transferase, UDP glucuronide transferase, and microsomal epoxide hydrolase) were 12% to 1000% higher in parenchymal cells than in non-parenchymal cells… Non-parenchymal cells showed more significant enzyme activity induction in animals pretreated with Aroclor 1254 compared to parenchymal cells. Furthermore, although enzyme activity in non-parenchymal cells was generally lower, they were susceptible to damage from bioinert xenobiotics, which could metabolize into active intermediates, even after induction…
The activity distribution of aminopyrine N-demethylase (APND), ethoxyhalothrin O-deethylase (ERRD), epoxide hydrolase (EH), and glutathione transferase (GST) was determined in control and Aroclor 1254-treated C57BL/6N and DBA/2N mouse parenchymal (PC) and non-parenchymal (NPC) cell populations. Furthermore, the metabolism of benzo[a]pyrene (BP) in parenchymal and non-parenchymal cells of two Aroclor 1254-treated mouse strains was examined… In the non-parenchymal cells of both strains, a low ratio of oxidative enzyme (epoxide aminopyrine N-demethylase and ethoxyhalothrin O-deethylase) to post-oxidative enzyme (epoxide hydrolase and glutathione transferase) activities was observed. …Except for ethoxyhalothrin O-deethylase activity in parenchymal and non-parenchymal cells of DBA/2N mice, Aroclor 1254 treatment enhanced the activities of all detected enzymes in parenchymal and non-parenchymal cells of both mouse strains. This is because the induction of ethoxyhalothrin O-deethylase by aromatic and halogenated aromatic compounds (e.g., Aroclor 1254) depends on the presence of cytoplasmic receptors, and DBA/2N mice have very low receptor affinity. After incubation of benzo[a]pyrene with parenchymal cells, non-parenchymal cells, or C57BL/6N mice treated with Aroclor 1254, large amounts of benzo[a]pyrene 9,10-dihydrodiol, 4,5-dihydrodiol, 7,8-dihydrodiol, quinone, 9-hydroxyl, and 3-hydroxyl derivatives were detected. The differences in the induction of aryl hydrocarbon hydroxylase (AHH) by sodium phenobarbital or Aroclor 1254 were investigated in four Drosophila strains. Adult Drosophila melanogaster (2 days old) of the Berlin-K, Oregon-K, Hag-79, and Hieng-R strains were transferred to vials containing a labeled cytochrome P-450 inducer. The concentrations of inducers were: 6.67 μg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 0.2 mg benzo[a]anthracene (BA), 0.15 mg Aroclor 1254, and 3.0 mg sodium phenobarbital. Three days after feeding, two male and two female fruit flies were mixed and homogenized for the fluorescence assay of aromatic hydrocarbon hydroxylase. Cytoplasmic samples from adult fruit flies were incubated with labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin or benzo[a]anthracene at 4°C for 1 hour. Aromatic hydrocarbon acceptors were analyzed by high-performance liquid chromatography (HPLC). Phenobarbital increased the aryl hydroxylase activity of the D-melanogaster-Berlin-K and D-melanogaster-Oregon-K strains by more than 10-fold, and the aryl hydroxylase activity of the D-melanogaster-Haag-79 and D-melanogaster-Hikone-R strains by approximately 2-fold. Except for the D-melanogaster-Hikone-R strain, Aroclor 1254 increased the aryl hydroxylase activity of all strains by 2- to 4-fold. Neither 2,3,7,8-tetrachlorodibenzo-dioxin nor benzo[a]anthracene significantly induced aryl hydroxylase expression in any of the four strains. In the presence of a 100-fold excess of unlabeled benzo[a]anthracene competitor, no saturable, high-affinity, low-capacity benzo[a]anthracene binding sites were detected in any of the four strains. In the presence of excess unlabeled 2,3,7,8-tetrachlorodibenzo-p-dioxins, high-affinity 2,3,7,8-tetrachlorodibenzo-p-dioxins binding sites were observed…
Polychlorinated biphenyls (PCBs) can be absorbed via inhalation, oral ingestion, and skin contact. They are transported in the blood and are typically bound to albumin. Due to their lipophilic nature, they tend to accumulate in lipid-rich tissues such as the liver, adipose tissue, and skin. PCB metabolism is very slow, and the rate of metabolism depends on the degree and location of chlorination. PCBs are metabolized into polar metabolites via the microsomal monooxygenase system under the catalysis of cytochrome P-450 enzymes. These polar metabolites can bind to glutathione and glucuronic acid. The main metabolites are hydroxylated products, which are excreted via bile and feces. Due to the slow metabolism of PCBs, they readily accumulate in tissues throughout the body. (L4, T6)

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Biological Half-Life
Serium: 1–3 years; [TDR, pp. 1–16] 1035]
In 1977 and 1985, serum polychlorinated biphenyl (PCB) concentrations were determined in 58 workers at a plant in Bloomington, Indiana. The plant had been using PCBs to produce capacitors prior to 1977. Low-chlorinated PCBs were quantified using Aroclor 1242, and high-chlorinated PCBs using Aroclor 1254. The median half-life of Aroclor 1242 was 2.6 years, and that of Aroclor 1254 was 4.8 years. However, the half-life was inversely proportional to the initial serum concentration…
In rat adipose tissue fed with Aroclor 1254, a biological half-life of approximately 200 days was recorded.

[1]. Morphological changes in livers of rats fed polychlorinated biphenyls: light microscopy and ultrastructure. Arch Environ Health. 1972 Nov;25(5):354-64.

Aroclor 1254 is a commercially available mixture of polychlorinated biphenyls (PCBs) with an average chlorine content of 54%. It is primarily composed of pentachlorobiphenyls (71.44%) and hexachlorobiphenyls (21.97%), but also contains monochloro, dichloro, trichloro, tetrachloro, hexachloro, and nonachloro homologues. PCBs are a class of 209 synthetic organic compounds, each with 1 to 10 chlorine atoms attached to a biphenyl ring in its molecule. PCBs were once produced as commercial mixtures, but were banned in the 1970s due to their bioaccumulation in the environment and harmful health effects. However, PCBs are not easily decomposed and remain in the environment. (L4)
A PCB mixture that induces the activity of hepatic microsomal UDP-glucuronyl transferase in response to thyroxine.
See also: Polychlorinated Biphenyls (Composition).

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Mechanism of Action
…This review summarizes the latest literature on the effects of endocrine disruptors (EDCs) on the neuroendocrine system, particularly hypothalamic gonadotropin-releasing hormone (GnRH) neurons (key cells involved in the regulation of reproductive function). This article focuses on two polychlorinated biphenyl mixtures (Aroclor 1221 and Aroclor 1254) and two organochlorine pesticides (methoxydiphenyl ether and chlorpyrifos). Experimental data on the effects of four urban environmental toxins on GnRH cells in vitro and in vivo are provided. In vitro results showed that all four toxins significantly affected hypothalamic gonadotropin-releasing hormone (GnRH) gene expression, cell survival, and neurite growth, confirming the direct effects of endocrine disruptors (EDCs) on GnRH cell lines. In vivo experiments revealed that three of the toxins (Aroclor 1221, methoxydiphenyl ether, and chlorpyrifos) significantly altered GnRH mRNA levels in female rats. Both in vitro and in vivo experimental results support the novel concept of chlorpyrifos as an endocrine disruptor. Combined with the literature, the results support the hypothesis that the neuroendocrine axis, particularly gonadotropin-releasing hormone (GnRH) neurons, is sensitive to urban environmental toxins, and that the reproductive and neurological effects of endocrine disruptors (EDCs) may be mediated at this level of the hypothalamus-pituitary-gonadal axis. Previous studies have shown that polychlorinated biphenyl (PCB) homologues disrupt intracellular Ca2+ homeostasis and protein kinase C (PKC) translocation in vitro… This study investigated the structure-activity relationship (SAR) of three PCB mixtures, 24 PCB homologues, and one dibenzofuran on PKC translocation by measuring the binding of (3)H-phorbol ester ((3)H-PDBu) in cerebellar granule cells (cultured for 7 days). All PCB mixtures significantly and in a concentration-dependent manner increased the binding of (3)H-PDBu. However, Aroclor 1016 and Aroclor 1254 were more potent than Aroclor 1260. Of the 24 homologues studied, the ortho- ortho homologues, such as 2,2',5,5'-tetrachlorobiphenyl (-TeCB), 2,2',4,6,6'-pentachlorobiphenyl (-PeCB), 2,2',4,6-tetrachlorobiphenyl (-TeCB), and 2,2'-dichlorobiphenyl (-DCB), were the most potent (E50 = 28-43 μM), while the non-ortho- ortho homologues, such as 3,3',4,4'-tetrachlorobiphenyl (-TeCB) and 3,3',4,4'-pentachlorobiphenyl (-PeCB), were ineffective. The potential contaminant 1,2,3,7,8-pentachlorodibenzofuran in the PCB mixture had no significant effect on the binding of (3)H-PDBu. Structure-activity relationship analysis of these homologues revealed that: (i) homologues with ortho-chlorine substitution, such as 2,2'-DCB (EC50 = 43 +/- 3 uM) or ortho- or lateral (meta-, para-)chlorine substitution, such as 2,2',5,5'-TeCB (EC50 = 28 +/- 3 uM) and 2,2'4,6-TeCB (EC50 = 41 +/- 6 uM), were the most potent; (ii) homologues with only para substitution, such as 4,4'-DCB, or homologues with high lateral content but no ortho substitution, such as 3,3',4,4',5,5'-HCB, were ineffective; (iii) the increase in chlorination degree was not significantly correlated with the effectiveness of these homologues, although hexachloride and heptachloride were less effective than dichloride and tetrachloride. Low lateral substitution, especially the absence of para substitution, or maintaining a low lateral substitution even in the presence of ortho substitution, is likely the most important structural requirement for the in vitro activity of these PCB homologues in neuronal preparations. Aroclor 1248 (2 mg/kg/day) and 1254 (5 mg/kg/day) induced the expression of a 3-methylcholanthrene-type mixed-function oxidase in the liver of adult female cynomolgus monkeys 69–122 days post-mortem. Intraperitoneal injection of 1000 mg/kg of Aroclor 1248 and 1254 produced a mixed-mode induction (including 3-methylcholanthrene induction) in mouse livers 66 hours post-administration. The same dose of Aroclor 1016 did not induce the expression of the 3-methylcholanthrene-type enzyme in mice. These monkey results are consistent with the hypothesis that PCB isomers capable of inducing aryl hydroxylases and causing a blue shift in the cytochrome peak are associated with increased toxicity. However, mice showed no response to Aroclor 1016, suggesting that the toxicity of Aroclor 1016 in young monkeys may not be due to the production of isomers with a similar effect to 3-methylcholanthrene. In rat liver, the ability of Aroclor 1254 to promote enzyme-altering foci was determined using a priming/promoting bioassay. Rats underwent partial hepatectomy (2/3) and were injected with diethylnitrosamine (DENA) 24 hours later. Aroclor 1254 was administered to each rat at days 7, 28, and 49 after DENA injection, with some rats sacrificed 21 days after each Aroclor injection. In the livers of rats treated with Aroclor 1254 on day 7 or 28, the levels of gamma-glutamyl transferase were elevated. A single oral dose of Aroclor 1254 enhanced the appearance of enzyme-altering foci. For more complete data on the mechanism of action of Aroclor 1254 (out of 18), please visit the HSDB record page.

C12H5CL5

326.4331

323.883

11097-69-1

40470

Light yellow, viscous liquid
Colorless to pale-yellow, viscous liquid or solid (below 50 degrees F)

1.5±0.1 g/cm3

392.2±37.0 °C at 760 mmHg

95.86°C (estimate)

193.6±23.9 °C

0.0±0.9 mmHg at 25°C

1.620

6.36

0

0

1

17

259

0

ClC1C=CC(C2C=CC=C(Cl)C=2Cl)=C(Cl)C=1Cl

AUGNBQPSMWGAJE-UHFFFAOYSA-N

InChI=1S/C12H5Cl5/c13-8-3-1-2-6(10(8)15)7-4-5-9(14)12(17)11(7)16/h1-5H

1,2,3-trichloro-4-(2,3-dichlorophenyl)benzene

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)