Absorption, Distribution and Excretion
Limited specific information is available on the oral absorption of Aroclor 1254. Pregnant ferrets that ingested a single oral dose of Aroclor 1254 (approx 0.06 mg/kg) absorbed approximately 85% of the initial amount. Studies predominately of individual chlorobiphenyl congeners indicate, in general, that PCBs are readily and extensively absorbed by animals. These studies have found oral absorption efficiency on the order of 75 to > 90% in rats, mice and monkeys. A study of a non-Aroclor 54% chlorine PCB mixture prepared by the investigators provides direct evidence of absorption of PCBs in humans after oral exposure, and indirect evidence of oral absorption of PCBs by humans is available from studies of ingestion of contaminated fish by the general population. There are no quantitative data regarding inhalation absorption of PCBs in humans but studies of workers exposed suggest that PCBs are well absorbed by the inhalation and dermal routes. PCBs distribute preferentially to adipose tissue and concentrate in human breast milk due to its high fat content.
When Aroclor 1254 was fed to pheasants either as a single dose of 50 mg or as 17 weekly doses of 12.5 or 50 mg, up to 82% was absorbed from the gastrointestinal tract and up to 50 mg/kg (wet weight) were found in their eggs.
In Sherman rats given doses of 10 or 50 mg/kg body weight/day Aroclor 1254 on days 7-15 of pregnancy, the average PCB concentrations in fetuses taken by Caesarean section on day 20 of pregnancy were 0.63 and 1.38 mg/kg, resp, compared with less than 0.12 mg/kg in controls.
In cows fed 200 mg/day Aroclor 1254 for 60 days, the average concn in milk fat was 60 mg/kg (measured between the 40th and 60th days of feeding).
For more Absorption, Distribution and Excretion (Complete) data for Aroclor 1254 (19 total), please visit the HSDB record page.

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Metabolism / Metabolites
The metabolism of PCBs in experimental animals has been extensively reviewed. Many substrates have been tested, and the PCBs were usually administered by the oral or parenteral routes. In general, these studies showed that the metabolism rate of PCBs depends on the number and position of chlorine atoms on the phenyl ring and on the animal species. In rats, the elimination half-lives of four PCBs with one, two, five, or six chlorines increased as the number of chlorines increased. The decreased excretion rate with increasing chlorination was directly related to the decreased rate of metabolism of the more highly chlorinated congeners. Sheep liver microsomes converted 2,2',5-triCB to at least 5 more polar metabolites within 1 min and at least 10 metabolites by 15 min; however, within the homologous series, 2,2',5,5'-tetraCB and 2,2',4,5,5'-pentaCB were oxidized to only 3 metabolites at rates 7- and 14-fold slower, respectively. Not only does the number of chlorines affect the rate of biotransformation, but the position of the chlorines on the phenyl rings is also critical. This was demonstrated in rats, which excreted four symmetrical hexachlorobiphenyls at different rates depending on the chlorine positions. As the number of unsubstituted meta positions or adjacent unsubstituted carbon atoms increases, the percentage of the dose excreted increases. The major hydroxylated PCB metabolite in rat plasma after administration of 25 mg/kg Aroclor 1254 in peanut oil by gavage is 4-hydroxy-2,3,3',4',5-pentaCB. From days 1 to 14 after exposure, this metabolite is found at concentrations 7-10 times the concentration of the major PCB 153.
The metabolism of PCBs following oral and parenteral administration in animals has been extensively studied and reviewed, but studies in animals following inhalation or dermal exposure are lacking. Information on metabolism of PCBs in humans is limited to occupationally exposed individuals whose intake is derived mainly from inhalation and dermal exposure. In general, metabolism of PCBs depends on the number and position of the chlorine atoms on the phenyl ring of the constituent congeners (i.e., congener profile of the PCB mixture) and animal species. Although only limited data are available on metabolism of PCBs following inhalation exposure, there is no reason to suspect that PCBs are metabolized differently by this route. Data exist on the in vitro hepatic metabolism and in vivo metabolic clearance of 2,2',3,3',6,6'-hexachlorobiphenyl and 4,4'-dichlorobiphenyl congeners in humans, monkeys, dogs and rats. The hexachlorobiphenyl congener is a constituent of Aroclor 1254. For each congener, the Vmax values for metabolism in the monkey, dog and rat are consistent with the respective metabolic clearance values found in vivo. Thus, the kinetic constants for PCB metabolism obtained from the dog, monkey and rat hepatic microsomal preparations were good predictors of in vivo metabolism and clearance for these congeners. In investigations directed at determining which species most accurately predicts the metabolism and disposition of PCBs in humans, the in vitro metabolism of these congeners was also studied using human liver microsomes. Available data suggest that metabolism of PCBs in humans would most closely resemble that of the monkey and rat. For example, the in vitro apparent Km and Vmax are comparable between humans and monkeys. These studies show consistency between the in vitro and in vivo findings and collectively indicate that metabolism of the two congeners is similar in monkeys and humans.
... To study the possible role of non-parenchymal cells in the metabolism of xenobiotics, populations of non-parenchymal and parenchymal cells (PC) were prepared from rats and various xenobiotic metabolizing enzyme activites investigated. The specific activity of every enzyme studied (ethoxyresorufin deethylase, benzphetamine demethylase, glutathione transferase, UDP glucuronosyltransferase, and microsomal epoxide hydrolase) was 12 to 1000% higher in the parenchymal than in the non-parenchymal populations ... The non-parenchymal cells demonstrated a more dramatic induction of enzyme activities in Aroclor 1254-pretreated animals than did the parenchymal. Moreover, despite the generally lower enzyme activities, even after induction, the non-parenchymal were damaged by biologically inert xenobiotics which can be metabolized to reactive intermediates ...
The distribution of aminopyrine N-demethylase (APND), ethoxyresorufin O-deethylase (ERRD), epoxide hydrolase (EH), and glutathione transferase (GST) activities in parenchymal (PC) and non-parenchymal (NPC) cell populations of control and Aroclor 1254-treated C57BL/6N and DBA/2N mice was determined. Furthermore, the metabolism of benzo(a)pyrene (BP) in parenchymal and non-parenchymal of both Aroclor 1254-treated mice strains was examined ... In non-parenchymal cells of both strains a low ratio of oxidative (epoxide aminopyrine N-demethylase and ethoxyresorufin O-deethylase) post-oxidative (epoxide hydrolase and glutathione transferase) enzyme activities was observed. ... Treatment with Aroclor 1254 enhanced all the enzyme activities measured in parenchymal and non-parenchymal of both mice strains with the exception of ethoxyresorufin O-deethylase in parenchymal and non-parenchymal of DBA/2N mice. This is due to the fact that the induction process of ethoxyresorufin O-deethylase by aromatic and halogenated aromatic compounds such as Aroclor 1254 depends upon the presence of a cytosolic receptor with a high affinity for this type of inducers and the DBA/2N mice have a very poor affinity receptor. After incubating benzo(a)pyrene with parenchymal or non-parenchymal or Aroclor 1254-treated C57BL/6N mice significant amounts of 9,10-dihydrodiol, 4,5-dihydrodiol, 7,8-dihydrodiol, quinone, 9-hydroxy, and 3-hydroxy derivatives of benzo(a)pyrene were detected.
Differences in aryl-hydrocarbon-hydroxylase (AHH) inducibility by sodium phenobarbital or Aroclor 1254 were investigated in four strains of Drosophila-melanogaster. Berlin-K, D-melanogaster-Oregon-K, D-melanogaster-Haag-79, and D-melanogaster-Hikone-R adults (2 days old) were transferred to vials containing labeled cytochrome P-450 inducer. Concentrations of the inducers were 6.67 ug 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. After 3 days of feeding, two males and two females were combined and homogenized for the fluorometric assay of aryl-hydrocarbon-hydroxylase. Cytosolic samplers from D melanogaster adults were incubated with labeled 2,3,7,8-tetrachlorodibenzo-p-dioxin or benzo(a)anthracene for 1 hr at 4 °C. High performance liquid chromatography was performed for the Ah receptor. Phenobarbital induced aryl-hydrocarbon-hydroxylase activity more than 10 fold in D-melanogaster-Berlin-K and D-melanogaster-Oregon-K and about 2 fold in D-melanogaster-Haag-79 and D-melanogaster-Hikone-R. Aroclor 1254 induced aryl-hydrocarbon-hydroxylase activity 2 to 4 fold in all the strains except D-melanogaster-Hikone-R. There was no significant aryl-hydrocarbon-hydroxylase induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin or benzo(a)anthracene in any of the four strains. In the presence of a 100 fold excess of nonlabeled benzo(a)anthracene competitor, no saturable high affinity low capacity benzo(a)anthracene binding moiety could be demonstrated in any of the four strains. High affinity 2,3,7,8-tetrachlorodibenzo-p-dioxin binding sites were observed by an excess of nonlabeled 2,3,7,8-tetrachlorodibenzo-p-dioxin ...
PCBs are absorbed via inhalation, oral, and dermal routes of exposure. They are transported in the blood, often bound to albumin. Due to their lipophilic nature they tend to accumulate in lipid-rich tissues, such as the liver, adipose tissue, and skin. Metabolism of PCBs is very slow and varies based on the degree and position of chlorination. PCBs are metabolized by the microsomal monooxygenase system catalyzed by cytochrome P-450 enzymes to polar metabolites that can undergo conjugation with glutathione and glucuronic acid. The major metabolites are hydroxylated products which are excreted in the bile and faeces. The slow metabolism of PCBs means they tend to accumulate in body tissues. (L4, T6)

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Biological Half-Life
Serum: 1-3 years; [TDR, p. 1035]
In 1977 and 1985, serum polychlorinated biphenyl (PCB) concentrations were determined for 58 workers in a Bloomington, Indiana, factory that used polychlorinated biphenyls (PCBs) in capacitor manufacture until 1977. Less chlorinated PCBs were quantitated as Aroclor 1242, and more highly chlorinated PCBs were quantitated as Aroclor 1254. The median half-life was 2.6 yr for Aroclor 1242 and 4.8 y for Aroclor 1254. However, the half-life varied inversely with the initial serum concentration ...
A biological half-life of about 200 days was recorded in the fat of rats after feeding with Aroclor 1254.

[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 commercial mixture of PCBs with an average chlorine content of 54%. It is composed of mainly pentachlorobiphenyls (71.44%) and hexachlorobuphenyls (21.97%) and also includes mono-, bi-, tri, tetra-, hexa, and nonachlorinated homologs. Polychlorinated biphenyls (PCBs) are a group of 209 synthetic organic compounds with 1-10 chlorine atoms attached to biphenyl. PCBs were manufactured as commercial mixtures but banned in the 1970's because they were found to bioaccumulate in the environment and cause harmful health effects. However, PCBs do not break down readily and are still found in the environment. (L4)
A mixture of polychlorinated biphenyls that induces hepatic microsomal UDP-glucuronyl transferase activity towards thyroxine.
See also: Polychlorinated Biphenyls (component of).

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Mechanism of Action
... This article reviews the current literature on endocrine-disrupting chemical (EDC) effects on the neuroendocrine system, particularly at the level of hypothalamic gonadotropin-releasing hormone (GnRH) neurons, the key cells involved in the regulation of reproductive function. The focus of this article is on two polychlorinated biphenyl mixtures (Aroclor 1221, Aroclor 1254) and two organochlorine pesticides (methoxychlor and chlorpyrifos). Some experimental data are presented for each of the four urban environmental toxicants on GnRH cells in vitro and in vivo. The results of in vitro experiments indicate that all four of the toxicants profoundly affect hypothalamic GnRH gene expression, cell survival, and neurite outgrowth, demonstrating direct effects of EDCs on a GnRH cell line. In in vivo experiments, three of the toxicants (Aroclor 1221, methoxychlor, and chlorpyrifos) caused significant alterations in GnRH mRNA levels in female rats. Both the in vitro and in vivo findings support the novel concept of chlorpyrifos as an EDC. The results, taken together with the literature, support the hypothesis that the neuroendocrine axis, and specifically GnRH neurons, are sensitive to urban environmental toxicants, and that reproductive and neurologic effects of EDCs may be mediated at this level of the hypothalamic-pituitary-gonadal axis.
... Previous reports indicate that polychlorinated biphenyl (PCB) congeners in vitro perturbed cellular Ca2+ homeostasis and protein kinase C (PKC) translocation ... The structure-activity relationship (SAR) of 3 PCB mixtures, 24 PCB congeners, and 1 dibenzofuran /have now been studied/ for their effects on PKC translocation by measuring (3)H-phorbol ester ((3)H-PDBu) binding in cerebellar granule cells (7 days in culture). All the PCB mixtures studied increased (3)H-PDBu binding significantly and in a concentration-dependent manner. However, Aroclor 1016 and Aroclor 1254 were more potent than Aroclor 1260. Of the 24 congeners studied, di-ortho congeners such as 2,2',5,5'-tetrachlorobiphenyl (-TeCB), 2,2',4,6,6'-pentachlorobiphenyl (-PeCB), 2,2',4,6-TeCB, and 2,2'-dichlorobiphenyl (-DCB) were the most potent (E50 = 28-43 uM) while non-ortho congeners such as 3,3',4,4'-TeCB and 3,3',4,4'5-PeCB were not effective. The potential contaminant of PCB mixtures, 1,2,3,7,8-pentachlorodibenzofuran had no significant effect on (3)H-PDBu binding. The SAR among these congeners revealed: (i) congeners with ortho-chlorine substitution such as 2,2'-DCB (EC50 = 43 +/- 3 uM) or ortho-lateral (meta, para) chlorine substitution such as 2,2',5,5'-TeCB (EC50 = 28 +/- 3 uM) and 2,2'4,6-TeCB (E50 = 41 +/- 6 uM) were most potent; (ii) congeners with only para-substitution such as 4,4'-DCB or high lateral content in the absence of ortho-substitution such as 3,3',4,4',5,5'-HCB were not effective; and (iii) increased chlorination was not clearly related to the effectiveness of these congeners, although hexa- and heptachlorination was less effective than di- and tetrachlorination. Low lateral substitution, especially without para-substitution, or lateral content in the presence of ortho-substitution, may be the most important structural requirement for the in vitro activity of these PCB congeners in neuronal preparations.
Aroclor 1248 (2 mg/kg /day) and 1254 (5 mg/kg/day) produced 3-methylcholanthrene-type of mixed-function oxidase induction in livers of adult female cynomolgus monkeys after 69-122 days when animals were moribund. Administration ip at a concentration of 1000 mg/kg produced a mixed pattern of induction in mouse liver 66 hr after treatment, (including a 3-methylcholanthrene-type induction). The same dose of Aroclor 1016 did not produce 3-methylcholanthrene-type enzyme induction in mice. Results in monkeys are consistent with hypothesis that PCB isomers capable of inducing aryl hydrocarbon hydroxylase and causing a blue shift in cytochrome peak are associated with increased toxicity. However, the lack of response with Aroclor 1016 in mice suggested that the reported toxicity of Aroclor 1016 to infant monkeys may not result from isomers producing a 3-methylcholanthrene-like effect.
Ability of Aroclor 1254 to promote enzyme-altered foci was determined in initiation/promotion bioassay in rat liver. Initiation was accomplished in rats that received a 2/3 partial hepatectomy followed in 24 hr by diethylnitrosamine (DENA). Aroclor 1254 was admin to each rat 7, 28, and 49 days after the DENA, and some rats were killed 21 days after each dose of Aroclor. Liver of rats that received Aroclor 1254 on either day 7 or on day 28 contained in increased level of gamma-glutamyltranspeptidase. Aroclor 1254 enhanced the appearance of enzyme-altered foci after only a single oral dose.
For more Mechanism of Action (Complete) data for Aroclor 1254 (18 total), 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.)