PRODUCTS

PCMC (PARA CHLORO META CRESOL)

CAS No. : 59-50-7

PCMC is the organic compound with the formula ClC6H4OH. It is a monochlorinated m-cresol. It is a white or colorless solid that is only slightly soluble in water. As a solution in alcohol and in combination with other phenols, it is used as an antiseptic and preservative. It is a moderate allergen for sensitive skin.[3]
PCMC is prepared by chlorination of m-cresol.

CAS No. : 59-50-7
EC No. : 200-431-6

Synonyms:
4-Chloro-3-methylphenol; p-Chlorocresol; cresol; p-chloro-m-cresol; PCMC; Chlorocresol; Preventol; CMK; CMP; Chloroxylenol (4-chloro-3,5-dimethylphenol); 4-Chloro-3-methylphenol; Chlorocresol; 59-50-7; 4-Chloro-m-cresol; p-Chloro-m-cresol; p-Chlorocresol; Phenol, 4-chloro-3-methyl-; Parol; Ottafact; Baktol; 4-Chloro-3-cresol; Candaseptic; Baktolan; Parmetol; Peritonan; Raschit; Aptal; Rasen-Anicon; Preventol CMK; 4-Chloro-5-methylphenol; PCMC; Preventol CMK; Raschit K; p-Chlor-m-cresol; 2-Chloro-5-hydroxytoluene; 6-Chloro-3-hydroxytoluene; 3-METHYL-4-CHLOROPHENOL; 2-Chloro-hydroxytoluene; Chlorcresolum; Chlorkresolum; Chlorocresolo; Chlorokresolum; Perol; m-Cresol, 4-chloro-; Chloro-3-cresol; Parachlorometacresol; Rcra waste number U039; 4-Chloro-3-methyl phenol; NSC 4166; 4-chloro-meta-cresol; Clorocresolo [DCIT]; Clorocresol [Spanish]; Caswell No. 185A; Chlorocresolum [Latin]; para-Chloro-meta-cresol; Clorocresol [INN-Spanish]; Chlorocresolum [INN-Latin]; CCRIS 1938; HSDB 5198; UNII-36W53O7109; 4-Chloro-1-hydroxy-3-methylbenzene; EINECS 200-431-6; RCRA waste no. U039; EPA Pesticide Chemical Code 064206; CHEBI:34395; 1-Chloro-2-methyl-4-hydroxybenzene; DSSTox_RID_76291; Chlorocresolum; Clorocresol; Clorocresolo; 4-Chloro-3-methylphenol, 99+%; CAS-59-50-7; 4-chloro-3-methyl-phenol; Lysochlor; Chlorocresol [USAN:INN:NF]; Chlorocresol, NF; 2p7a; 4-chlor-3-methylphenol; Chlorocresol (NF/INN); 4-chloro-5-methyl-phenol; WLN: QR DG C; EC 200-431-6; SCHEMBL12344; Phenol, 4-chloro-5-methyl-; 4-Chloro-3-methylphenol, 99%; CTK3J0561; NE10170; NSC-756680; Chlorocresol (4-Chloro-3-methylphenol); 4-Chloro-3-methylphenol, technical grade; AC-14332; Q208; SC-16335; 4-Chloro-3-methylphenol, analytical standard; 4-Chloro-3-methylphenol, >=98.0% (HPLC); 4-Chloro-3-methylphenol 100 microg/mL in Methanol; Q-200453; Preventol CMK; 43M; 6-Chloro-3-hydroxytoluene; 2-Chloro-5-hydroxytoluene; 3-Methyl-4-chlorophenol; p-Chloro-m-cresol; 4-Chloro-m-cresol; Sodium p-chloro-m-cresol; Sodium p-chloro-m-cresolate; 15733-22-9; 4-Chloro-m-cresol sodium salt; Phenol, 4-chloro-3-methyl-, sodium salt (1:1); Caswell No. 756; Chlorocresol sodium; Sodium 4-chloro-3-methylphenolate; Sodium 4-chloro-m-cresolate; p-Chloro-m-cresol, sodium salt; Sodium 4-chloro-3-methylphenoxide; EINECS 239-825-8; EPA Pesticide Chemical Code 064205; sodium-4-chloro-3-methylphenolate; Sodium 3-methyl-4-chlorophenolate; P-CHLORO-M-CRESOL SODIUM SALT; 3-Methyl-4-chlorophenol, sodium salt; 1-PHENYL-1-CHLOROETHANE SODIUM SALT; 2-chloro-5-hydroxytoluene sodium salt, AldrichCPR; 4-Chloro-3-methylphenol; 4-CHLORO-M-CRESOL; PARA CHLORO META CRESOL; 1-chloro-2-methyl-4-hydroxybenzene; 2-chloro-5-hydroxytoluene; 3-methyl-4-chlorophenol; 4-chloro-5-methylphenol; 6-chloro-3-hydroxytoluene; p-chloro-m-cresol; p-chlorocresol; para-chloro-meta-cresol; para-chloro-meta-cresol; 4-chloro-m-cresol; 59-50-7; P-chloro-m-cresol; Parol; Phenol, 4-chloro-3-methyl-; Baktol; Candaseptic; Baktolan; Ottafact; Parmetol; Peritonan; Raschit; Aptal; P-chlorocresol; Rasen-anicon; Preventol Cmk; Raschit K; P-chlor-m-cresol; Pcmc; Chlorcresolum; Chlorkresolum; Chlorocresolo; Chlorokresolum; M-cresol, 4-chloro-; 2-chloro-hydroxytoluene; Perol; 4-chloro-5-methylphenol; 2-chloro-5-hydroxytoluene; 4-chloro-3-methyl Phenol; 6-chloro-3-hydroxytoluene; Chloro-3-cresol; Parachlorometacresol; 3-methyl-4-chlorophenol; Clorocresolo [dcit]; Chlorocresolum Clorocresol; 4-chloro-m-cresol; 59-50-7; P-chloro-m-cresol; Parol; Phenol, 4-chloro-3-methyl-; Baktol; 4-chloro-3-cresol; Candaseptic; Baktolan; Ottafact; Parmetol; Peritonan; Raschit; Aptal; P-chlorocresol; Rasen-anicon; Preventol Cmk; Raschit K; P-chlor-m-cresol; Pcmc; Chlorcresolum; Chlorkresolum; Chlorocresolo; Chlorokresolum; M-cresol, 4-chloro-; 2-chloro-hydroxytoluene; Perol; 4-chloro-5-methylphenol; 2-chloro-5-hydroxytoluene; 4-chloro-3-methyl Phenol; 6-chloro-3-hydroxytoluene; Chloro-3-cresol; Parachlorometacresol; 3-methyl-4-chlorophenol; Clorocresolo [dcit]; Clorocresol [spanish]; Caswell No; Chlorocresolum [latin]; Rcra Waste Number U039; Rcra Waste No; Clorocresol [inn-spanish]; Chlorocresolum [inn-latin]; 4-chloro-1-hydroxy-3-methylbenzene; Epa Pesticide Chemical Code 064206

PCMC

PCMC (also hydroxytoluene) are organic compounds which are methylphenols. They are a widely occurring natural and manufactured group of aromatic organic compounds, which are categorized as phenols (sometimes called phenolics). Depending on the temperature, PCMC can be solid or liquid because they have melting points not far from room temperature. Like other types of phenols, they are slowly oxidized by long exposure to air, and the impurities often give samples of PCMC a yellowish to brownish red tint. PCMC have an odor characteristic to that of other simple phenols, reminiscent to some of a "coal tar" smell. The name PCMC reflects their structure, being phenols, and their traditional source, creosote.

Structure and production
In its chemical structure, a molecule of PCMC has a methyl group substituted onto the ring of phenol. There are three forms (isomers) of PCMC: ortho-PCMC (o-PCMC), meta-PCMC (m-PCMC), and para-PCMC (p-PCMC). These forms occur separately or as a mixture, which can also be called PCMC or more specifically, triPCMC.[citation needed] About half of the world's supply of PCMC are extracted from coal tar. The rest is produced by hydrolysis of chlorotoluenes or the related sulfonates. Another method entails methylation of phenol with methanol over a solid acid catalyst, often comprising magnesium oxide or alumina. Temperatures above 300 °C are typical. Anisole converts to PCMC under these conditions.

Applications
PCMC are precursors or synthetic intermediates to other compounds and materials, including plastics, pesticides, pharmaceuticals, and dyes.
Most recently, PCMC have been used to create a breakthrough in manufacturing carbon nanotubes at scale that are separated and not twisted, without additional chemicals that change the surface properties of the nanotubes.

Health effects
When PCMC are inhaled, ingested, or applied to the skin, they can be very harmful. Effects observed in people include irritation and burning of skin, eyes, mouth, and throat; abdominal pain and vomiting; heart damage; anemia; liver and kidney damage; facial paralysis; coma; and death.

Breathing high levels of PCMC for a short time results in irritation of the nose and throat. Aside from these effects, very little is known about the effects of breathing PCMC, for example, at lower levels over longer times.
Ingesting high levels results in kidney problems, mouth and throat burns, abdominal pain, vomiting, and effects on the blood and nervous system.
Skin contact with high levels of PCMC can burn the skin and damage the kidneys, liver, blood, brain, and lungs.
Short-term and long-term studies with animals have shown similar effects from exposure to PCMC. No human or animal studies have shown harmful effects from PCMC on reproduction.
It is not known what the effects are from long-term ingestion or skin contact with low levels of PCMC.
The Occupational Safety and Health Administration has set a permissible exposure limit at 5 ppm (22 mg/m3) over an eight-hour time-weighted average, while the National Institute for Occupational Safety and Health recommends a limit of 2.3 ppm (10 mg/m3).

PCMC appears as a pinkish to white crystalline solid with a phenolic odor. Melting point 64-66°C. Shipped as a solid or in a liquid carrier. Soluble in aqueous base. Toxic by ingestion, inhalation or skin absorption. Used as an external germicide. Used as a preservative in paints and inks.
PCMC and chloracetamide are used in medications, glues, and cosmetics as preservatives.

At all concentrations of /4-chloro-m-cresol/ (4-cmc), the increase in baseline force was significantly greater in the /malignant hyperthermia susceptible/ (MHS) group compared to the /malignant hyperthermia negative/ MHN group (P<0.05). Muscle from 15 MHS patients responded to 4-cmc with increasing force at a threshold concentration of 75 umol/L or less, whereas muscle from 23 MH-non-susceptible (MHN) patients had thresholds of 100 umol/L or more. The accuracy of the PCMC test was thus 100% (95% confidence limits 90.75-100%) at a threshold of 75 umol/L. Amplitude of contractures at 2 mmol/L caffeine was not different from contractures at 75 umol/L of 4-cmc in either the MHS or the MHN group (P>0.05). In vivo concentrations of PCMC from clinical use of insulin and somatropin are estimated to be 20 times less than the threshold concentration and thus these drugs seem safe in MH patients. 4-chloro-m-cresol may be a suitable aid to clarify puzzling results of standard testing of MH susceptibility.

Four groups of conventional female albino guinea pigs, three per group, were used to determine the bioavailability of PCMC. Occlusive patches of 0.2 mL of a 5% PCMC aqueous suspension stabilized with Carbomer 941, a saturated aqueous solution of 0.38% PCMC, 5% PCMC in olive oil/acetone (4:1), or 5% PCMC in propylene glycol were applied for 24 hr. After 96 hr, the animals were killed and the skin at the site of patch testing was removed for analysis (the patches were kept for analysis to determine the amount of PCMC remaining in the patch material). Fractional sampling of the urine and feces was performed to determine the rate of absorption of PCMC. An additional three animals had been injected with PCMC intraperitoneally to determine the excretion rate. However, no free PCMC was found, indicating rapid metabolism. In determining bioavailability, the calculations were based on the assumption that the saturated PCMC solution is 0.4% (w/v), corresponding to 0.8 mg in 0.2 mL, and that 0.2 mL of the 5% PCMC preparations contained 10 mg of the chemical. The results indicated that 25% of the aqueous PCMC (stabilized with carbomer 941) and 46% of the saturated aqueous PCMC solution remained in the patches. Only 0.2% of the aqueous PCMC (stabilized with carbomer 941) and 0.5% of the saturated aqueous PCMC solution was found in the skin at the patch site. This was compared to 65% of the PCMC in propylene glycol and 66% of the PCMC in olive oil/acetone solutions remaining in the patch; and 0.7% and 1.6%, respectively found in the skin at the patch site. The authors conclude that PCMC was more bioavailable from the aqueous preparations. After 96 hr, 0.2 and 0.5% PCMC was detected at the patch test site in the animals dosed with 5% and saturated aqueous PCMC, respectively, and 0.7 and 1.6% PCMC were found in the skin of the animals patch tested with 5% PCMC in olive oil/acetone and propylene glycol, respectively.

A pharmacokinetic study was performed in which rats were dosed orally with 300 mg/kg PCMC. PCMC reportedly was eliminated rapidly through the kidneys. Additionally, there is no likelihood of cumulation effects. A corresponding examination of fatty and hepatic tissues from rats that were fed 150-1500 ppm PCMC for up to 13 week reported no indication of an accumulation of PCMC in these tissues.
PCMC contains less than 0.1% 3-methylphenol (m-cresol) as measured by HPLC and GC-MS.
In skeletal muscle sarcoplasmic reticulum, 4-chloro-m-cresol was found to be a potent activator of Ca2+ release mediated by a ruthenium red/caffeine-sensitive Ca2+ release channel. In cerebellar microsomes, this compound released Ca2+ from an inositol-1,4,5-trisphosphate-insensitive store, suggesting that there too it was acting at the ryanodine receptor level. When tested on PC12 cells, PCMC released Ca2+ from a caffeine- and thapsigargin-sensitive intracellular store. In addition, the compound was capable of releasing Ca2+ after pretreatment of PC12 cells with bradykinin, suggesting that it acts on a channel contained within an intracellular Ca2+ store that is distinct from that sensitive to inositol-1,4,5-trisphosphate. Structure-activity relationship analyses suggest that the chloro and methyl groups in PCMCs are important for the activation of the ryanodine receptor Ca2+ release channel.
PCMC are incompatible with bases, acid chlorides, acid anhydrides, and oxidizing agents. Corrodes steel, brass, copper and copper alloys (NTP, 1992).

Based on the reviews of the generic data for the active ingredients p-chloro-m-cresol, the Agency has sufficient information on the health effects of PCMC and on its potential for causing adverse effects in fish and wildlife and the environment. The Agency has determined that PCMC products, labeled and used as specified in this Reregistration Eligibility Decision, will not pose unreasonable risks or adverse effects to humans or the environment. Therefore, the Agency concludes that products containing PCMC for all uses are eligible for reregistration.
Only PCMC, Thymol, and o-Cymen-5-ol are reported to be in current use, with the highest concentration of use at 0.5% for o-Cymen-5-ol in perfumes ...Several of these cresols increase the dermal penetration of other agents, including azidothymidine...The Cosmetic Ingredient Review (CIR) Expert Panel noted some of these ingredients may increase the penetration of other cosmetic ingredients and advised cosmetic formulators to take this into consideration...

A method is described for the confirmation of PCMCs in human urine. Hydrolyzed urine samples were analyzed by gas chromatography and liquid chromatography with electrochemical detection and results compared. It is sensitive for PCMCs at low ppb range.
To examine the effect on the leakage of low molecular weight cytoplasmic constituents from Staphylococcus aureus using phenolics singly and in combination, and to see if the observations could be modelled using a non-linear dose response. The rate of potassium, phosphate and adenosine triphosphate leakage was examined in the presence of PCMC and m-cresol. Individually, leakage was observed only at long contact times or high concentrations. Combined at these ineffective concentrations, the cytoplasmic pool of all constituents studied was released within minutes. Both PCMC and m-cresol were shown to have non-linear dose responses. A rate model for the combinations, which takes account of these non-linear responses, accurately predicted the observations. Antimicrobials, which when used alone exhibit a non-linear dose response, will also give a non-linear dose response in combination. The simple linear-additive model ignores the concept of the dilution coefficient and will always describe the phenomenon of synergy for combinations where one or more of the components has a dilution coefficient greater than one. This has been borne out by examination of the purported prime lesion of PCMC and m-cresol, alone and in combination. Studies aimed at producing synergistic mixtures of antimicrobials, which ignore the non-linear additive effect, may waste valuable research effort looking for a physiological explanation for an apparent synergy, where none, in-fact, exists. Patents granted on the basis of analyses using the linear-additive model for combinations of compounds with non-linear dose responses may no longer be supportable.

A single occlusive patch of a below-irritation dose of PCMC (concentration not specified) was applied for 48 hr to 363 patients with allergic contact dermatitis. Upon scoring after 96 hr, three patients had positive reactions to PCMC.
Consecutive eczema patients were tested with the International Contact Dermatitis Research Group (ICDRG) standard patch test series, which included PCMC-containing biocides. Reactions were scored according to the recommendations of the ICDRG. Of 1462 patients tested with 2% PCMC in petrolatum, only five had positive patch test results and six had irritant reactions; none of the positive results were clinically explainable.
In a Draize test performed using male subjects, groups of 98, 88, and 66 subjects were induced with 5, 10, or 20% PCMC in petrolatum, respectively, for 3-5 week. Ten 48-72 hr applications of 0.5 g of the test material were made under an occlusive patch to the upper lateral portion of each subject's arm. Following an approximately 2 week non-treatment period, subjects of all three groups were challenged with a 72 hr patch containing 5% PCMC in petrolatum. None of the subjects in the three test groups responded to the challenge patch.

Acute Exposure/ Groups of male Wistar rats were given a single oral dose of 400 mg/kg PCMC in peanut oil; controls were dosed with an equivalent amount of peanut oil only. All animals were killed 60 hr after dosing, and hepatic tissue was removed from the center of the right lobe of the liver for examination by electron microscopy. After dosing, the animals' behavior changed; after 30 minutes, the animals were uneasy and had "ruffled-up" coats. These signs diminished after 1 hr, but they were replaced by long "apathetic motions". After 24 hr until study termination, the hair coats were again altered. At necropsy, the liver appeared slightly enlarged and was a pale red color with pale gray spots. Light microscopy findings included a distinct dilation of the sinusoids with an activation of the Kupffer cells. The intercellular spaces were enlarged, and there were numerous vacuoles found in the cytoplasm. In electron micrographs, outpouchings of cell membranes were observed. A greater than normal number of lysosomes were around the bile canaliculi after dosing. Also, there was an increase in the number of mitochondria, many membrane-surrounded vacuoles, alterations in the intercellular space and in the rough endoplasmic reticulum, and an increase in the number and size of gap junctions. Additionally, the bile canaliculi were dilated and had irregularities and side branches which extended into the cytoplasm of adjacent hepatocytes.

Acute Exposure/ The trypan blue method of Hoppe was used to determine the dermal irritation potential of PCMC. Groups of rabbits, two per group (sex not specified), were given a single application of 0.2% PCMC in normal saline or 0.4 or 0.8% PCMC in 1% Tween in normal saline. The site of application was four areas on the abdominal region and the duration of contact was 0.4 mL injected intradermally within 10-15 min. Twenty minutes after dosing, 1 mL/kg of 1% trypan blue was injected intravenously and the color at the injection sites was observed for 3 hr. The maximal irritation score (scale not stated) was 4 for 0.2 and 0.4% and 8 for 0.8% PCMC.
Sixty Stamm Pirbright White guinea pigs, 30 per sex, were used in a sensitization study performed according to the method of Magnusson and Kligman. Induction consisted of intradermal injections, two with PCMC and one with Freund's adjuvant, followed 1 week later with a topical application of 0.1 mL of 1 and 25% PCMC in Lutrol (site of application not stated). The challenge, performed after 2 weeks, consisted of cutaneous application of 12.5, 22, and 50% PCMC in Lutrol and 100% PCMC to the flank of the animals. A 25% of PCMC was "strongly sensitizing" while a 1% solution was "weakly sensitizing".

3-Methyl-4-chlorophenol (PCMC)'s production may result in its release to the environment through various waste streams; it's use as a disinfectant and a preservative will result in its direct release to the environment. If released to air, a vapor pressure of 5.0X10-2 mm Hg at 25 °C indicates 3-methyl-4-chlorophenol (PCMC) will exist solely as a vapor in the atmosphere. Vapor-phase 3-methyl-4-chlorophenol (PCMC) 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 hours. 3-Methyl-4-chlorophenol (PCMC) absorbs light at wavelengths >290 nm, and therefore may be susceptible to direct photolysis by sunlight. If released to soil, 3-methyl-4-chlorophenol (PCMC) is expected to have moderate mobility based upon a Koc of 490. The pKa of 3-methyl-4-chlorophenol (PCMC) is 9.55, indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil surfaces is expected to be an important fate process based upon an estimated Henry's Law constant of 2.4X10-6 atm-cu m/mole. 3-Methyl-4-chlorophenol (PCMC) may volatilize from dry soil surfaces based upon its vapor pressure. Half-lives of 4.2 days in acidic sandy loam with a low organic content and 1.4 days in basic sandy silt loam with a higher organic carbon content suggest biodegradation may be an important environmental fate process in soil. If released into water, 3-methyl-4-chlorophenol (PCMC) is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Biodegradation test results are conflicting. 3-Methyl-4-chlorophenol (PCMC) was not degraded in 4 weeks using an activated sludge inoculum in the Japanese MITI test perhaps due to microbial toxicity from the high concentration of the test chemical but reached 20-65% of the Theoretical Oxygen Demand after 28 days in the Closed Bottle Test. 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 18 and 134 days, respectively. A BCF range of 5.5 to 13 suggests bioconcentration in aquatic organisms is low. 3-Methyl-4-chlorophenol (PCMC) is not expected to undergo hydrolysis in the environment because phenols are generally resistant to hydrolysis. Occupational exposure to 3-methyl-4-chlorophenol (PCMC) may occur through inhalation and dermal contact with this compound at workplaces where 3-methyl-4-chlorophenol (PCMC) is produced or used. Monitoring data indicate that the general population may be exposed to 3-methyl-4-chlorophenol (PCMC) via ingestion of drinking water, where the chemical has been inadvertently formed during chlorination treatment, and dermal contact with this compound and other products containing 3-methyl-4-chlorophenol (PCMC).

The Koc of 3-methyl-4-chlorophenol (PCMC) is 490(1). According to a classification scheme(2), this Koc value suggests that 3-methyl-4-chlorophenol (PCMC) is expected to have moderate mobility in soil. The pKa of 3-methyl-4-chlorophenol (PCMC) is 9.55(3), indicating that this compound will exist partially in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). The chemical was found to be mobile in an activated carbon-sand filter system; this was considered to be indicative of a low adsorption potential in soil systems(5). 3-Methyl-4-chlorophenol (PCMC) concentration balance was 0.167 ug/L influent, not detected effluent from Steinhaeule, Neu-Ulmin, a major municipal sewage plant in Germany, sampled on March 11, 1998(6).
The Henry's Law constant for 3-methyl-4-chlorophenol (PCMC) is estimated as 2.4X10-6 atm-cu m/mole(SRC), based on its vapor pressure, 5.0X10-2 mm Hg(1), and water solubility, 3,830 mg/L(2). This Henry's Law constant indicates that 3-methyl-4-chlorophenol (PCMC) is expected to volatilize from water surfaces(3). Based on this Henry's Law constant, the volatilization half-life from a model river (1 m deep, flowing 1 m/sec, wind velocity of 3 m/sec)(3) is estimated as 18 days(SRC). The volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind velocity of 0.5 m/sec)(3) is estimated as 134 days(SRC). 3-Methyl-4-chlorophenol (PCMC)'s Henry's Law constant indicates that volatilization from moist soil surfaces may occur(SRC). 3-Methyl-4-chlorophenol (PCMC) is not expected to volatilize from dry soil surfaces(SRC) based upon its vapor pressure(1).
NIOSH (NOES Survey 1981-1983) has statistically estimated that 175,929 workers (24,335 of these were female) were potentially exposed to 3-methyl-4-chlorophenol (PCMC) in the US(1). Occupational exposure to 3-methyl-4-chlorophenol (PCMC) may occur through inhalation and dermal contact with this compound at workplaces where 3-methyl-4-chlorophenol (PCMC) is produced or used. Monitoring data indicate that the general population may be exposed to 3-methyl-4-chlorophenol (PCMC) via ingestion of drinking water, where the chemical has been inadvertently formed during chlorination treatment, and dermal contact with this compound and other products containing 3-methyl-4-chlorophenol (PCMC)(SRC).

Para Chloro Meta Cresoll (PCMC) that we offer is formulated under the strict vigilance of experts so as to ensure superior quality. It is tested on various quality parameters prior to its final dispatch. We are named among the renowned Manufacturers, Suppliers and Exporters of Para Chloro Meta Cresoll (PCMC). We have the capability to deliver retail as well as bulk orders for Para Chloro Meta Cresoll (PCMC) within the stipulated time frame.

p-chloro-m-cresol (PCMC) is an active substance with a specified minimal purity of 99.8%. The analysis of representative production batches of the active substance were provided. The relevant impurity m-cresol specification is 0.1%. Considering the classification of m-cresol and its content in the active substance (0.1%), mcresol is not considered as a substance of concern for (eco)toxicological point of view. The value of dissociation constant of 9.4 indicates that PCMC can be found in salt form at higher pH levels. The active substance is the acid form of PCMC. All studies used to set physico-chemical, toxicological and ecotoxicological values were performed on the acid form and are consistent with a purity of production of 99.9% (nominal value found in the 5-batch analysis).

The literature analysis clearly showed that especially if the concentration of PCMC is in the efficient range no acquired resistance occur. In addition, using bactericidal concentrations, the risk of development of cross-resistance or co-resistance is in general low, considering the multi-site activity of PCMC. Since it interacts with many different targets of the bacterial cell wall, the risk of developing resistance mechanisms is minimal. Few authors described insufficient sporocidal effects of PCMC and explained this by development of resistance. However, PCMC is not efficacious against microbial spores and such well-known lack of sporicidal efficacy cannot be interpreted as result of resistance development.

Repeated toxicity studies
Oral application of PCMC for 4 weeks to rats caused no adverse effects. Therefore the oral subacute NOAEL is 790 and 920 mg/kg/day for males and females, respectively. 4-week dermal application of PCMC to rats caused moribundity, reduced body weight gain, due to reduced food consumption, increased water intake and urinary tract effects (ureterectasia, blood clots in the bladder), and local skin effects at the application site (erythema, oedema, wounds and crustification, and increase in skin thickness) at 1000 mg/kg bw/day. No effect was observed at the lower dose of 200 mg/kg bw/day which is considered as the sub-acute NOAEL for systemic and local effects to rats. In another dermal study with rabbits, dermal treatment with PCMC for 21 days causes no systemic effects but only local skin reactions at the lower tested dose 10 mg/kg bw/day. Therefore, no NOAEC can be determined for local effects, only a LOAEC of 10 mg/kg/day is retained. In an inhalation study in Wistar rats, focused on respiratory effects, some local effects were observed. The NOAEL and the NOAEC determined from this study are 50 mg/m3.
Sub-chronic oral administration of PCMC to rats for 3 months produced no adverse effects at doses up to and including 120 mg/kg bw/day (males) and 170 mg/kg bw/day (females). No NOAEL has been determined in this study. Dermal application of PCMC to rats for 13 weeks causes no effects. The sub-chronic dermal NOEL is considered to be 500 mg/kg bw/day.

Experimental data
To refine the assessment and justify its use, the applicant provided 3 experimental studies measuring the level of PCMC in pig (Stroech KD, 2012a; Kellner G, 2011) and broiler (chicken) (Stroech KD, 2012b) tissues after rearing on an area treated with a disinfectant containing PCMC alone or PCMC and 2-benzyl-4 chlorophenol. The purpose of these 3 studies was to investigate the level of PCMC residue in the edible parts
of fattening pigs (meat, fat, liver, kidney, skin) and broiler chickens (meat, liver, skin and fat), after one single application in the shed for the first two studies. In the third study, disinfection occurred before each transfer of animals from a pen to another (4 disinfections during the whole breeding period). In all the studies, the shed was disinfected with a ready-to-use solution containing PCMC. After drying, pigs or chickens were introduced and fed.
PCMC is stable to hydrolysis at pH values of 4, 7 and 9 (50° C). Therefore, it is not to be expected that hydrolytic processes will contribute to the degradation of PCMC in the aquatic environment.

Biodegradation
No key study dealing with the degradation of PCMC in STP has been provided. However supportive simulation studies, monitoring reports and publications indicate that an efficient elimination of PCMC occurs in industrial as in domestic STPs. Considering that PCMC is readily biodegradable (10-day window fulfilled), a half-life of 0.03 days has been applied for STP compartment for the exposure calculation. Two studies concerning the biodegradation in water sediment systems have been provided. The first one shows that the dissipation of PCMC is rapid in the whole system (DT50, 12°C ≤ 3.6 d) as in the water phase (DT50, 12°C ≤ 3.3 d). The mineralization rate was over 20% and the bound residues remained below 55%. This first study clearly indicates that no extractable metabolite occurred over 10% in the sediment. As the picture was less clear for the metabolite in the water phase, a further study has been provided in order to better separate and quantify the metabolites. This second study allows confirming that no metabolite of concern occurred in the water phase, the only metabolite near the threshold of 10% being phenol (9.9 % of applied radioactivity). A non-key laboratory study and analysis of sediment and water in German rivers support the high aerobic biodegradation rate in aquatic compartment. Additionally, several insights dealing with the metabolic pathway of PCMC in water have been provided. Only supportive data have been provided for the assessment of the degradation of PCMC in soil and default degradation value from the TGD10 for a readily biodegradable substance has been therefore applied to calculate concentrations of PCMC in soil (DT50: 30 days).

Toxins
Most neurotoxins produce either diffuse encephalopathy or peripheral neuropathy. Only ethylene glycol, trichlorethylene, and PCMC exposure cause selective cranial nerve toxicity. Ethylene glycol is antifreeze. Ingestion causes facial diplegia, hearing impairment, and dysphagia. Trichlorethylene intoxication can cause multiple cranial neuropathies but has a predilection for the trigeminal nerve. It was once a treatment for tic douloureux. PCMC, a compound used in the industrial production of heparin, caused recurrent unilateral facial palsy in one exposed worker. Inhalation of the compound caused tingling of one side of the face followed by weakness of the muscles. The neurological disturbance was brief, relieved by exposure to fresh air, and could be reproduced experimentally.

p-Chlorocresol (p-chloro-m-cresol; PCMC; brand name: Preventol CMK) possesses disinfectant and antiseptic properties. PCMC is used in various preparations for skin disinfection and wounds. It also used as a preservative in creams and other preparations for external use which contain water. For use as a disinfectant such as a hand wash, it is commonly dissolved in alcohol in combination with other phenols. It is a moderate allergen for sensitive skin. PCMC produces potentially life-threatening effects which include dermatitis, which are responsible for the discontinuation of PCMC therapy. The symptomatic adverse reactions produced by PCMC are more or less tolerable and if they become severe, they can be treated symptomatically, these include hypersensitivity reactions, irritation of eyes.