Absorption, Distribution and Excretion
In chronic feeding studies, DDD, like DDT, was stored in body fat, but its mobilization and excretion rates were faster than DDT after resuming a normal diet. Sheep were orally administered DDD for 28 consecutive days. DDE appeared in fat as a metabolite of DDD. DDD showed two peaks in the blood; one at 8 hours post-administration and the other at 32 hours post-administration. Tetrachlorodiphenyl ethane (p,p-DDD) was found in the urine of New Zealand red rabbits exposed to cigarette smoke containing labeled TDE. Tetrachlorodiphenyl ethane and TDEE were found in fat, vital organs, and other tissues. DDD was quantitatively analyzed in maternal blood, placental, and umbilical cord blood samples from women who experienced stillbirth and live birth. The stillbirth samples showed higher levels of organochlorine pesticides compared to matched control groups. For more complete data on the absorption, distribution, and excretion of DDD (15 in total), please visit the HSDB records page.

---

Metabolism/Metabolites
In pigeons (Columba liva)...feeding DDD.../results/a small amount of DDE residue. DDD is rapidly metabolized and completely converted to 2,2-bis(p-chlorophenyl)-1-chloroethylene.
...DDD...is present in peanut oil...injected into fertilized Leghorn eggs or added to feed for chicks hatched from untreated eggs. No significant difference was observed between the two treatments. ...p,p'-DDD produces o,p'-DDD, 2,2-bis(p-chlorophenyl)-1-chloroethylene (DDMU), 2,2-bis(p-chlorophenyl)-1-chloroethane (DDMS), 2,2-bis(p-chlorophenyl)ethylene (DDNU), 2,2-bis(p-chlorophenyl)ethanol (DDOH), bis(p-chlorophenyl)acetic acid (DDA), DDM, and dichlorobenzophenone (DBP).
The tissues of the Mexican bean beetle (Epilachna varivestis muls) contain DDT dechlorination enzyme activity and are able to…dechlorinate dibenzo-dioxin (DDD).
In adult volunteers, after ingesting DDD, di(p-chlorophenyl)acetic acid (DDA) is excreted in the urine. DDD is readily degraded, converting to DDA via a series of intermediates, and is rarely present in the general population as a stored metabolite.
For more complete data on DDD metabolism/metabolites (15 in total), please visit the HSDB record page.
DDD is absorbed in the stomach and intestines, then enters the lymphatic system and is transported throughout the body, eventually integrating into adipose tissue. DDD metabolism is primarily carried out by cytochrome P-450 enzymes in the liver and kidneys. Its metabolite, mainly DDA (di(p-chlorophenyl)acetic acid), is excreted in the urine. (L85)

---

Biological half-life
……Calculations show that the elimination half-life of methoxydiphenyl ether in sheep is 10 days; while the values for DDT, DDD and DDE are 90 days, 26 days and 223 days, respectively.

Toxicity Summary
DDD toxicity occurs through at least four mechanisms, possibly all simultaneously. DDD reduces transmembrane potassium transport. DDD inhibits the inactivation of voltage-gated sodium channels. These channels normally activate (open) but inactivate (close) slowly, interfering with the active transport of sodium ions out of nerve axons during repolarization, leading to neuronal hyperexcitability. DDD inhibits neuronal adenosine triphosphatases (ATPases), particularly Na+K+-ATPase and Ca2+-ATPase, which play crucial roles in neuronal repolarization. DDD also inhibits the ability of calmodulin (a calcium mediator) in neurons to transport calcium ions, which are essential for neurotransmitter release. All these inhibited functions reduce the rate of depolarization and increase the sensitivity of neurons to weak stimuli that would not elicit a response in fully depolarized neurons. DDD is also thought to have adverse effects on the reproductive system by mimicking endogenous hormones and binding to estrogen and androgen receptors. (T10, L85)

---

Toxicity Data
LD50: 113 mg/kg (oral, rat) (L138)

---

Interactions
...Administration of o,p'-DDD at a dose of 50 mg/kg/day over 14 days resulted in progressive hypotensive failure in dogs injected with adrenaline or norepinephrine, without affecting the acceleration of heart rate and immediate pressor response of these drugs. Hypotensive failure was associated with decreased cardiac contractility and reduced plasma volume. The latter was likely due to intravascular fluid loss rather than histamine release. Pre-administration of prednisolone significantly prevented hypotensive states.
If cortisol...DDD... increases the production of hydroxylated metabolites and leads to a change in excretion patterns from glucuronide to other conjugates. ...When used in combination with testosterone, DDD also leads to an increase in the production of hydroxylated metabolites...

---

Non-human toxicity values
Rat dermal LD50 >10,000 mg/kg
Mouse oral LD50 1466 mg/kg
Rat oral LD50 113 mg/kg
Rat oral LD50 3,400 mg/kg
Rabbit dermal LD50 1,200 mg/kg

[1]. Conversion of p,p' -DDT to p,p' -DDD by intestinal flora of the rat. Science. 1966;151(3717):1527-1528.

[2]. Cytogenetic status of human lymphocytes after exposure to low concentrations of p,p'-DDT, and its metabolites (p,p'-DDE, and p,p'-DDD) in vitro. Chemosphere. 2012;87(11):1288-1294.

According to an independent committee of scientific and health experts, DDD (dichlorodiphenyl dichloroethane) may be carcinogenic. Dichlorodiphenyl dichloroethane is a colorless crystalline solid, insoluble in water, and sinks in water. It is toxic if inhaled, absorbed through the skin, or ingested. It was once used as an insecticide. DDD is a chlorophenylethane, a compound of 2,2-bis(p-chlorophenyl)ethane with two chlorine atoms substituted at the 1 position. It is a metabolite of the organochlorine insecticide DDT, belonging to the exogenous metabolite class. It is an organochlorine insecticide, belonging to the monochlorobenzene class of compounds, and is also a chlorophenylethane. DDD,P,P'- is an isomer of dichlorodiphenyl dichloroethane (an organochlorine insecticide) and is a component of commercial DDT mixtures. DDT was once a widely used insecticide, but due to its toxicity and bioaccumulation, it is now banned globally for use in agricultural production. However, its application in disease vector control remains limited. (L84)
An organochlorine insecticide with mild skin irritation. (From Merck Index, 11th edition, p. 482)
Mechanism of Action
...At a dose of... (60 mg/kg, intravenously), all isomers of TDE inhibited ACTH-induced steroid production in dogs, but the m,p'-isomer achieved 50% inhibition in just 27 minutes, compared to 87 minutes for the o,p'-isomer and 4–18 hours for the p,p'-isomer. Significant time-dependent effects were observed between the percentage inhibition of ACTH-induced steroid production, disruption of normal cellular structure in the zona fasciculata and zona reticularis of the adrenal cortex, and the degree of mitochondrial damage in these regions caused by the three isomers. In this study, we determined whether the DDT isomers p,p'-DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane], o,p'-DDT [1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethane] and their metabolites p,p'-DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane], o,p'-DDD [1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethane], and p,p'-DDE affected adrenal cortex function. 1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene, o,p'-DDE (1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethylene), and p,p'-DDA (2,2-bis(p-chlorophenyl)acetic acid) can bind to and transcribe and activate the human estrogen receptor (hER). New results from competitive binding assays show that o,p'-DDD, o,p'-DDE, and p,p'-DDT, as well as the known environmental estrogen o,p'-DDT, specifically bind to the hER, but their affinity for the hER is approximately 1000 times weaker than that of estradiol. Conversely, only o,p'-DDT, not p,p'-DDT, binds to the rat estrogen receptor. Furthermore, two yeast expression reporter systems were constructed to detect whether DDT isomers and metabolites can transcribe and activate the hER. The results showed that o,p'-DDT metabolites could transactivate hER or LexA-hER fusion proteins, but their potency was only 140 to 300 times weaker than estradiol. DDT isoforms and metabolites that bind to hER in vitro can trigger estrogen receptor-mediated transcription of the lacZ reporter gene in yeast systems. Furthermore, DDT isoforms and metabolites that transactivate hER have an additive effect when used in combination with or simultaneously with estradiol. DDT isoforms and metabolites that trigger transcription in yeast reporter expression systems can also stimulate two estrogen endpoints in estrogen-responsive MCF-7 cells: progesterone receptor induction and hER downregulation. Therefore, in MCF-7 cells and yeast reporter expression systems, certain DDT isoforms and metabolites can act directly as agonists and activate hER at human tissue concentrations. We combined in vitro experiments to evaluate whether DDT metabolites can interact with the progesterone receptor pathway in yeast expressing human progesterone receptor (hPR) and in T47D human breast cancer cells expressing endogenous hPR. In transcriptional activation assays in yeast and T47D cells, o,p'-DDT and its metabolites p,p'-DDT, o,p'-DDD, p,p'-DDD, o,p'-DDE, p,p'-DDE, p,p'-DDA, and DDOH all inhibited progesterone-induced reporter gene activity in a dose-dependent manner. None of the DDT metabolites possessed hPR agonist activity. Whole-cell competitive binding assays using T47D cells indicated that the inhibition of progesterone-dependent activity by DDT metabolites may occur through both hPR-dependent and hPR-independent pathways. Our results, along with previous reports on the interactions of DDT metabolites with estrogen and androgen receptors, suggest that these environmental chemicals may interact with multiple hormone receptor signaling pathways. This study investigated the mechanism of action of o,p'-DDD on adrenal steroid production in rainbow trout (Oncorhynchus mykiss) in vitro. Acute exposure to o,p'-DDD inhibited ACTH-stimulated cortisol secretion, while cell viability was significantly reduced only at the highest tested concentration (200 μM o,p'-DDD). In cells exposed to o,p'-DDD, the concentration of cAMP analog (dibutyryl cyclic adenosine monophosphate) required to stimulate cortisol secretion was higher than the concentration required to inhibit ACTH-stimulated cortisol synthesis. o,p'-DDD inhibited fossclin-stimulated cortisol secretion and cAMP production, as well as NaF-stimulated cAMP production, in a concentration-dependent manner. Conversely, o,p'-DDD stimulated basal cortisol secretion but had no effect on basal cAMP production. At physiologically relevant concentrations of pregnenolone, o,p'-DDD enhanced pregnenolone-stimulated cortisol secretion; while at pharmacological concentrations of pregnenolone, o,p'-DDD inhibited cortisol secretion. These results indicate that the cAMP generation step is the target of o,p'-DDD-mediated ACTH-stimulated disruption of adrenal steroid production in rainbow trout, but other downstream targets, such as steroid-producing enzymes responsible for cortisol synthesis, may also be affected.

C14H10CL4

320.034

317.953

72-54-8

p,p'-DDD-d8;93952-20-6

6294

White to off-white solid powder

1.4±0.1 g/cm3

405.7±40.0 °C at 760 mmHg

94-96 °C

199.3±24.7 °C

0.0±0.9 mmHg at 25°C

1.599

5.39

0

0

3

18

218

0

AHJKRLASYNVKDZ-UHFFFAOYSA-N

InChI=1S/C14H10Cl4/c15-11-5-1-9(2-6-11)13(14(17)18)10-3-7-12(16)8-4-10/h1-8,13-14H

1-chloro-4-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene

Rothane; Dilene; TDE

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.

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

DMSO : ~100 mg/mL (~312.46 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

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