NIPACIDE PX

NIPACIDE PX

Nipacide PX is a low toxicity biocide, para-chloro-3,5-m-xylenol. Offers efficiency against bacteria, fungi and yeast. Nipacide PX is provides complete microbiological protection of water-based paints in the wet state.

CAS No. : 88-04-0
EC No. : 201-793-8

Synonyms:
para-chloro-3,5-m-xylenol; Nipacide PX/Nipacide PX-R/Nipacide MX; Chloroxylenol; nipasit px; nipasid px; nipacid px; nipaside px; para-chloro-meta-xylenol; Chloroxylenol; 4-Chloro-3,5-dimethylphenol; PCMX; Dettol; 4-Chloro-3,5-dimethylphenol; chloroxylenol; 88-04-0; Dettol; 4-Chloro-3,5-xylenol; PCMX; Benzytol; p-Chloro-m-xylenol; 4-Chloro-3,5-xylenol; NIPACIDE PX; 4-Chloro-3-xylenol; 2-Chloro-m-xylenol; 2-Chloro-5-hydroxy-m-xylene; 2-Chloro-5-hydroxy-1,3-dimethylbenzene; 4-Chloro-3,5-dimethylphenol; Benzytol; Chloroxylenol; Dettol; Husept extra; Nipacide PX; Ottasept; Para-chloro-meta-xylenol; PCMX; Chloro-3,5-dimethylphenol; Chloro-3,5-xylenol; Chloro-5-hydroxy-m-xylene; Chloro-m-xylenol; Desson; Dimethyl-4-chlorophenol; Espadol; Septiderm-hydrochloride; PCMX; Xylenol, 4-chloro-.; 2-Chloro-m-xylenol; 4-Chloro-m-xylenol; Phenol, 4-chloro-3,5-dimethyl-; Ottasept; Desson; Espadol; Chloro-xylenol; Ottasept Extra; Nipacide PX; Husept Extra; p-Chloro-3,5-xylenol; Willenol V; 3,5-Dimethyl-4-chlorophenol; parachlorometaxylenol; Septiderm-Hydrochloride; Chloroxylenolum; Chlorxylenolum; Cloroxilenol; 2-Chloro-5-hydroxy-m-xylene; Dettol, liquid antiseptic; Nipacide MX; Parametaxylenol; RBA 777; 2-Chloro-5-hydroxy-1,3-dimethylbenzene; 4-Chloro-1-hydroxy-3,5-dimethylbenzene; C8H9ClO; 3,5-Xylenol, 4-chloro-; Caswell No. 218; Clorossilenolo [DCIT]; Chloroxylenol; PARA-CHLORO-META-XYLENOL; NSC 4971; Cloroxilenol [INN-Spanish]; Chloroxylenolum [INN-Latin]; UNII-0F32U78V2Q; 4-chloro-3,5-dimethyl-phenol; HSDB 7427; EINECS 201-793-8; 4-Chloro-3, 5-xylenol; EPA Pesticide Chemical Code 086801; 4-Chloro-3,5-dimethylphenol, 99%; Clorossilenolo; Vionexus; CAS-88-04-0; Camel (pesticide); Ayrtol; Chloroxylenol [USAN:INN:BAN]; Nipacide PX; Chloroxylenol(USAN; Chloroxylenol

Nipacide PX

Chloroxylenol, also known as para-chloro-meta-xylenol (Nipacide PX), is an antiseptic and disinfectant which is used for skin disinfection, and together with alcohol for cleaning surgical instruments. Nipacide PX is also used within a number of household disinfectants and wound cleaners. Nipacide PX is thought to act by disrupting microbial cell walls and inactivating cellular enzymes, and is less effective than some other available agents. Nipacide PX is available as a liquid.

History of Nipacide PX
Nipacide PX was first made in 1927. It is on the World Health Organization's List of Essential Medicines. It is sold in a number of formulations and under a number of brand names, including Dettol.
Soon after it was created parachlorometaxylenol was then called Nipacide PX, but this was thought to be a poor name and it was renamed Dettol. Then in 1932 it was marketed in Britain and in India. It had a white on green bottle with a white sword depicted. Nipacide PX is sold, in the same style bottle, in Argentina and Uruguay to this day.

Properties of Nipacide PX
Side effects are generally few but can include skin irritation. It may be used mixed with water or alcohol. Nipacide PX is most effective against gram-positive bacteria. It works by disruption of the cell wall and stopping the function of enzymes.

Uses of Nipacide PX
Nipacide PX is used in hospitals and households for disinfection and sanitation. It is also commonly used in antibacterial soaps, wound-cleansing applications and household antiseptics such as Dettol liquid (to which it contributes its distinctive odor), cream and ointments. Following independent laboratory testing specific Dettol products have demonstrated effectiveness against the Covid-19 virus (SARS-CoV-2) when used in accordance with the directions for use.

Side effects of Nipacide PX
Nipacide PX is not significantly toxic to humans, is practically non-toxic to birds, and is moderately toxic to freshwater invertebrates. It is highly toxic to fish, cats, and some amphibians and should not be used around them. Nipacide PX is a mild skin irritant and may trigger allergic reactions in some individuals.

Humans
Excessive exposure to Nipacide PX has the potential for causing death. It can be poisonous when swallowed and even when it is unintentionally inhaled. A medical study in Hong Kong which analyzed 177 cases of Dettol ingestion that resulted in emergency department treatment (95% of which were intentional), concluded that "Dettol poisoning resulted in serious complications in 7% of patients, including death."

Animals
Nipacide PX is toxic to many animals, especially cats. Phenolic compounds are of particular concern because cats are unable to fully metabolize them. A cat may swallow the product by licking its paws after they have come into contact with it.
In Australia, Nipacide PX spray has been shown to be lethal to cane toads, an invasive species that was introduced from Hawaii as a result of bad judgment in 1935. It had been hoped that the amphibian would control the cane beetle but it became highly destructive within the ecosystem. Spraying the disinfectant at close range has been shown to cause rapid death to toads. Nipacide PX is not known whether the toxins are persistent or whether they harm other Australian flora and fauna.
Owing to concerns over potential harm to other Australian wildlife species, the use of Nipacide PX as an agent for pest control was banned in Western Australia by the Department of Environment and Conservation in 2011.

Society and culture
A number of brand names are available. Nipacide PX is the active ingredient in Dettol. Nipacide PX comprises 4.8% of Dettol's total admixture, with the rest made up by pine oil, isopropanol, castor oil, soap and water.

Chloroxylenol (Nipacide PX) also called 4-Chloro-3, 5-dimethylphenol, is a white crystal. Nipacide PX is a secure, high-efficient, broad spectrum and low-toxic antiseptic. Nipacide PX has large potency to Gram-positive, Gram-negative, epiphyte and mildew approved by FDA . Nipacide PX has good chemical stability and doesn’t lose the activity in normal storage conditions. Solubility in water is 0.03 wt%, freely soluble in organic solvent such as alcohols, ethers, polyglycols, etc. and solutions of alkali hydroxides frequently used in personal clean care products.

This product (Nipacide PX) is low-poison antibacterial, frequently used in personal care products such as hand - cleaning detergent, soap, dandruff control shampoo and healthy products, etc. Common dosage in lotion as follows: 0.5~1wt% in liquid detergent, 1wt% in antibacterial handing detergent, 4.5~5 wt% in disinfectant. What’s more, Nipacide PX has been used in other fields such as glue, painting, textile, pulp, etc.

This study examines the bactericidal and fungicidal efficiency of parachlorometaxylenol (Nipacide PX) and its active ingredient, chlorxylenol at 10% and 20% concentrations, on four microbial isolates from abattoirs' (slaughter houses) floors in an open environment in Port Harcourt metropolis, Rivers State Nigeria. The study was carried out between the months of January 2005 and June 2006. Mixed culture of Vibrio species, Salmonella sp, Campylobacter sp and Candida albicans isolated from five different abattoirs: Agip, Trans -Amadi, Woji, Rumuodara and Rumuokoro: were used as test bacteria and fungi respectively, using agar diffusion and tranditional plate count methods. The four microbial isolates were exposed to parachlorometaxylenol (Nipacide PX) and chlorxylenol after the addition of quenching agent (QAC), at time interval starting from Omin, lOmin, 20min, 30min, 40,min, 50min,and 60min. Analysis of Variance (ANOVA) was calculated on the resistance and the susceptibility of these four isolates to the test disinfectants, the results showed that there was no significant difference in the test disinfectants effectiveness on these test organisms. The findings showed that Vibrio, Salmonella and Campylobacter were more sensitive to parachlorometaxylenol (Nipacide PX) also called Dettol, while Candida albicans was more sensitive to Chlorxylenol. Also observed from this work is candidiasis infection through cross-contamination can be taken care of in the body of its victim by washing in 10% chloroxylenol.

At ambient temperature, a 25% solution of Nipacide PX in isopropanol is not corrosive to stainless steel or aluminum. Brass is slightly affected as is mild steel. Mild steel is slightly affected by isopropanol alone.
Nipacide PX is stable when exposed to sunlight and humidity from ambient storage over 24 hours. It is also stable at elevated temperatures (54 °C). Choroxylenol is hydrolytically stable.

Drug Indication of Nipacide PX
The predominant medical applications for which Nipacide PX is formally indicated for therapeutic use is as an application to the skin for use in cuts, bites, stings, abrasions, and for use as antiseptic hand cleaner.
Nipacide PX is a substituted phenol which has been widely used for many years as an ingredient of antiseptic and disinfectant products intended for external use. Nipacide PX is known to be bactericidal in low concentration to a wide range of Gram positive and Gram negative bacteria.

Absorption
No Nipacide PX was detected in the blood following the dermal administration of 2 g of p-Nipacide PX in an ethanol/olive oil vehicle in human subjects. After a dose of 5 g, only traces were found, after 8 g, 1 mg % (1 mg/dL) was found in the blood after 3 hours, and 4 mg % (4 mg/dL) after 24 hours. After a dose of 20 g, 4 mg % (4 mg/dL) was measured after half an hour, and 1 mg % (1 mg/dL) was present at 72 hours. For antiseptic purposes, Nipacide PX is considered to be well-absorbed when applied to the skin.

Volume of Distribution
The only data available regarding the volume of distribution of Nipacide PX is the mean Vss of 22.45 L determined after 200 mg intravenous single dose of Nipacide PX was administered to healthy mongrel dog subjects.

Clearance
The only data available regarding the clearance of Nipacide PX is the mean clearance rate of 13.76 L/hr following a 200 mg intravenous single dose of the substance into healthy mongrel dog subjects. Moreover, in another study, when 8 g of Nipacide PX was administered dermal on a human subject in an alcohol/glycerin vehicle, 11% was excreted in 48 hours.

Metabolism/Metabolites
Certain animal studies have shown that following dermal application of Nipacide PX, that the absorption was rapid with a Cmax = 1-2 hours, and that the administered substance was excreted via the kidney with almost complete elimination within 24 hours. The primary metabolites discovered in the excreted urine were glucuronides and sulfates. Some Nipacide PX monographs liken its pharmacokinetic profile to that of another antiseptic - triclosan - which is rapidly excreted in the urine also as a glucuronide metabolite, as observed in the human model. Moreover, In one human subject administered 5 mg intragluteally, 14% was excreted with glucuronic acid and 17% with sulfuric acid at 3 days. Any Nipacide PX absorbed into the body is likely extensively metabolized by the liver and rapidly excreted, mainly in the urine, as sulphate and glucuronide conjugates.

One study estimated the mean terminal half-life and mean residence time after a 200 mg intravenous single dose of Nipacide PX in healthy mongrel dog subjects to be 1.7 and 1.69 hours, respectively. Alternatively, some product monographs liken Nipacide PX to a similar liquid antiseptic, triclosan, whose calculated urinary excretion half-life in man is approximately 10 hours.
As a phenol antiseptic, it is believed that the hydroxyl -OH groups of the Nipacide PX molecule binds to certain proteins on the cell membrane of bacteria, and disrupts the membrane so as to allow the contents of the bacterial cell to leak out. This allows Nipacide PX to enter the bacterial cell to bind further with more proteins and enzymes to disable the cell's functioning. At particularly high concentrations of Nipacide PX, the protein and nucleic acid content of targeted bacterial cells become coagulated and cease to function, leading to rapid cell death.

Pursuant to section 8(d) of TSCA, EPA promulgated a model Health and Safety Data Reporting Rule. The section 8(d) model rule requires manufacturers, importers, and processors of listed chemical substances and mixtures to submit to EPA copies and lists of unpublished health and safety studies. Nipacide PX is included on this list.

Section 4(g)(2)(A) of FIFRA calls for the Agency to determine, after submission of relevant data concerning an active ingredient, whether products containing the active ingredients are eligible for reregistration. The Agency has previously identified and required the submission of the generic (i.e. active ingredient specific) data required to support reregistration of products containing Nipacide PX active ingredients. The Agency has completed its review of these generic data, and has determined that the data are sufficient to support reregistration of all products containing Nipacide PX.

Drug products containing certain active ingredients offered over-the-counter (OTC) for certain uses. A number of active ingredients have been present in OTC drug products for various uses, as described below. However, based on evidence currently available, there are inadequate data to establish general recognition of the safety and effectiveness of these ingredients for the specified uses: Nipacide PX is included in topical acne drug products.

Toxicity Summary of Nipacide PX
As Nipacide PX is predominantly employed as an active ingredient in various liquids or creams as cleaners, disinfectants, or antiseptics that are generally designed to be used topically, it is widely accepted that the use of such liquids - when used appropriately - is unlikely to present a sufficient volume that could be ingested to cause any medical problems. In the event of accidental eye contact, was with Luke warm water. Nipacide PX is known to have a low systemic toxicity, even at dosage levels many times higher that those likely to be absorbed during normal usage of the agent.

Environmental Fate/Exposure Summary of Nipacide PX
Nipacide PX's production and use as an antibacterial, germicide, antiseptic and in mildew prevention may result in its release to the environment through various waste streams. If released to air, a vapor pressure of 0.1 mm Hg at 20 °C indicates Nipacide PX will exist solely as a vapor in the atmosphere. Vapor-phase Nipacide PX will be degraded in the atmosphere by reaction with photochemically-produced hydroxyl radicals; the half-life for this reaction in air is estimated to be 5.8 hours. Nipacide PX does not absorb at wavelengths >290 nm and has been reported to be stable to sunlight for up to 24 hours. If released to soil, Nipacide PX is expected to have low mobility based upon an estimated Koc of 1,400. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 5.1X10-7 atm-cu m/mole. Nipacide PX is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Volatilization from water surfaces is expected to be an important fate process based upon this compound's estimated Henry's Law constant. Estimated volatilization half-lives for a model river and model lake are 10 hours and 9 days, respectively. Degradation of Nipacide PX appears to be slower than other phenol derivatives. Studies in sewage showed 80-95% of the original compound remaining after 2 days and 60-70% remaining after 7 days. This is consistent with other studies that showed less than 40% degradation in activated sludge over 7 days. If released into water, Nipacide PX is not expected to adsorb to suspended solids and sediment based upon the estimated Koc. An estimated BCF of 66 suggests the potential for bioconcentration in aquatic organisms is moderate. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions. Occupational exposure to Nipacide PX may occur through inhalation and dermal contact with this compound at workplaces where Nipacide PX is produced or used. The most likely route of exposure to the general population is through dermal contact when using soaps or cleaning products that contain Nipacide PX as an antibacterial. A smaller population may be exposed to Nipacide PX when taking medications that contain Nipacide PX as an active ingredient.

Para-Chloro-Meta-Xylenol (Nipacide PX) is an antiseptic and disinfectant. Used for skin disinfection and cleaning surgical instruments. It is also used within a number of household disinfectants and wound cleaners.
Nipacide PX is an antimicrobial chemical compound used as a preservative to control bacteria, algae, and fungi in adhesives, emulsions, paints, cooling fluids, glue, cosmetics, hygiene products such as hair conditioners and deodorants, topical medications, urinary antiseptics and metal working fluids.  Liquid Nipacide PX solutions are used for cleaning and disinfecting wounds, abrasions and abscesses while creams are used for cuts, scratches, insect bites, and burns. Powders are used to treat problems of the feet and skin inflammations.

Uses of Nipacide PX:
Preservative in cooling fluids, creams, topical and urinary antiseptics. Chloroxylenol (Nipacide PX) acts against a wide range of bacteria. Liquids are used for the cleaning and disinfecting of wounds and abrasions as well as abscesses. The creams are used for cuts, scratches, insect bites, burns and similar problems. Powders can be used to treat tinea problems of the feet and skin inflammations. Also in pharmaceutical products, hair conditioners, toilet and deodorants, soaps, electrocardiogram paste, etc.
Chloroxylenol, or para-chloro-meta-xylenol (Nipacide PX), is an antiseptic and disinfectant agent used for skin disinfection and surgical instruments. Nipacide PX is found in antibacterial soaps, wound-cleansing applications, and household antiseptics. The halophenol is shown to be most effective against Gram positive bacteria where it disrupts the cell wall due to its phenolic nature 1. Nipacide PX is on the World Health Organization's List of Essential Medicines.

Nipacide PX is a substituted phenol which has been widely used for many years as an ingredient of antiseptic and disinfectant products intended for external use. It is known to be bactericidal in low concentration to a wide range of Gram positive and Gram negative bacteria.
As a phenol antiseptic, it is believed that the hydroxyl -OH groups of the Nipacide PX molecule binds to certain proteins on the cell membrane of bacteria, and disrupts the membrane so as to allow the contents of the bacterial cell to leak out. This allows Nipacide PX to enter the bacterial cell to bind further with more proteins and enzymes to disable the cell's functioning. At particularly high concentrations of Nipacide PX, the protein and nucleic acid content of targeted bacterial cells become coagulated and cease to function, leading to rapid cell death.
Volume of distribution
The only data available regarding the volume of distribution of Nipacide PX is the mean Vss of 22.45 L determined after 200 mg intravenous single dose of Nipacide PX was administered to healthy mongrel dog subjects 6,8.

Protein binding
One study determined the protein binding of Nipacide PX to be approximately 85.2% +/- 2.32% for serum albumin and 89.8% +/- 2.99% for whole human serum.
Metabolism
Certain animal studies have shown that following dermal application of Nipacide PX, that the absorption was rapid with a Cmax = 1-2 hours, and that the administered substance was excreted via the kidney with almost complete elimination within 24 hours. The primary metabolites discovered in the excreted urine were glucuronides and sulfates. Some Nipacide PX monographs liken its pharmacokinetic profile to that of another antiseptic - triclosan - which is rapidly excreted in the urine also as a glucuronide metabolite, as observed in the human model.
Moreover, In one human subject administered 5 mg intragluteally, 14% was excreted with glucuronic acid and 17% with sulfuric acid at 3 days 4.
Any Nipacide PX absorbed into the body is likely extensively metabolized by the liver and rapidly excreted, mainly in the urine, as sulphate and glucuronide conjugates.

Route of elimination of Nipacide PX
The major route of excretion is likely in urine 8,7, although some amounts may be found in bile and traces in exhaled air.
Half-life
One study estimated the mean terminal half-life and mean residence time after a 200 mg intravenous single dose of Nipacide PX in healthy mongrel dog subjects to be 1.7 and 1.69 hours, respectively 6,8. Alternatively, some product monographs liken Nipacide PX to a similar liquid antiseptic, triclosan, whose calculated urinary excretion half-life in man is approximately 10 hours.
Clearance of Nipacide PX
The only data available regarding the clearance of Nipacide PX is the mean clearance rate of 13.76 L/hr following a 200 mg intravenous single dose of the substance into healthy mongrel dog subjects.
Moreover, in another study, when 8 g of Nipacide PX was administered dermal on a human subject in an alcohol/glycerin vehicle, 11% was excreted in 48 hours.

Toxicity of Nipacide PX
As Nipacide PX is predominantly employed as an active ingredient in various liquids or creams as cleaners, disinfectants, or antiseptics that are generally designed to be used topically, it is widely accepted that the use of such liquids - when used appropriately - is unlikely to present a sufficient volume that could be ingested to cause any medical problems 7. In the event of accidental eye contact, was with Luke warm water 7.
Nipacide PX is known to have a low systemic toxicity, even at dosage levels many times higher that those likely to be absorbed during normal usage of the agent.

Drug overdose
There have been many cases of intoxication with oral Nipacide PX liquid, a widespread household disinfectant that contains Nipacide PX 4.8%, pine oil, and isopropyl alcohol. Nipacide PX was involved in 10% of hospital admissions related to self-poisoning in Hong Kong. In a retrospective study of 67 cases, serious complications were relatively common (8%) and these included aspiration of Nipacide PX with gastric contents, resulting in pneumonia, cardiopulmonary arrest, bronchospasm, adult respiratory distress syndrome, and severe laryngeal edema with upper airway obstruction. Of 89 patients, five developed minor hematemesis, in the form of coffee-colored or blood-stained vomitus. One patient had a gastroscopy performed on the day after admission, which showed signs of chemical burns in the esophagus and stomach. Gastroscopy in another patient on day 11, done to rule out an esophageal stricture, showed no abnormality. All patients with hematemesis recovered completely. The authors suggest that upper gastrointestinal hemorrhage after Nipacide PX ingestion tends to be mild and self-limiting. Gastroscopy, which may increase the risk of aspiration in patients with impaired consciousness, is not required unless other causes of gastrointestinal bleeding are suspected. Furthermore, Nipacide PX poisoning can be associated with an increased risk of aspiration, possibly caused by the use of gastrointestinal lavage in 88% of the patients and vomiting in 62%.
Of 121 patients who ingested Nipacide PX 200–500 ml, three developed renal impairment, as evidenced by raised plasma urea and creatinine. Two of these patients also had serious complications, including aspiration leading to pneumonia and adult respiratory distress syndrome; one died. Renal impairment only appears to be observed when relatively large amounts of Nipacide PX are ingested.

Nipacide PX is used in cosmetic products as an antimicrobial at concentrations up to 5.0 percent. It is absorbed through the human skin and gastrointestinal tract. Following oral ingestion by a human of a product formulated with Nipacide PX, both free and conjugated Nipacide PX were detected in the urine.
Nipacide PX at 100 percent concentration was a moderate irritant to the rabbit eye, whereas a 0.1 percent aqueous Nipacide PX solution was a nonirritant to rabbit skin. Nipacide PX was nonmutagenic in the Salmonella mutagenesis assay, both with and without metabolic activation. No carcinogenicity or adequate teratogenicity studies have been reported.
In clinical studies, formulations containing up to 1 .O percent Chloroxyleno1 were nonsensitizing and essentially nonirritating to the skin. The incidence of skin sensitization among 1752 dermatitis patients exposed to 1 .O percent Nipacide PX was less than 1 .O percent. On the basis of the available information included in this report, it is concluded that Nipacide PX is safe as a cosmetic ingredient in the present practices of use.