3,3′,4′,5-Tetrachlorosalicylanilide

351.004

351.01

214-576-8

HNE676755I

DTXSID4040767

Crystalline solid|Crystals

29242998

49.3

5.87 (est)

1.6676 (rough estimate)

161 °C

408.1±45.0 °C(Predicted)

200.6ºC

1.6200 (estimate)

In water, 0.16 mg/L at 25 deg C (est)

3.0X10-10 mm Hg at 25 deg C (est)

Henry's Law constant = 4.8X10-11 atm-cu m/mol at 25 °C (est)

pKa = 6.8 (phenol) (est)

Fluoresces under ultraviolet light

R22

Xn

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The following drug products were withdrawn or removed from the market because such drug products or components of such drug products were found to be unsafe or not effective. The following drug products may not be compounded under the exemptions provided by section 503A(a) of the Federal Food, Drug, and Cosmetic Act. 3,3',4,5'-Tetrachlorosalicylanilide (all drug products containing 3,3',4,5'-tetrachlorosalicylanilide) is included on this list.|Use of certain halogenated salicylanilides as ingredients in cosmetic products. (a) Halogenated salicylanilides (tribromsalan (TBS,3,4?,5-tribromosalicylanilide), dibromsalan (DBS,4?5-dibromosalicylanilide), metabromsalan (MBS, 3,5 - dibromosalicylanilide) and 3,3?,4,5?- tetrachlorosalicylanilide (TCSA)) have been used as antimicrobial agents for a variety of purposes in cosmetic products. These halogenated salicylanilides are potent photosensitizers and cross-sensitizers and can cause disabling skin disorders. In some instances, the photosensitization may persist for prolonged periods as a severe reaction without further exposure to these chemicals. Safer alternative antimicrobial agents are available. (b) These halogenated salicylanilides are deleterious substances which render any cosmetic that contains them injurious to users. Therefore, any cosmetic product that contains such a halogenated salicylanilide as an ingredient at any level for any purpose is deemed to be adulterated under section 601(a) of the Federal Food, Drug, and Cosmetic Act. (c) Any cosmetic product containing these halogenated salicylanilides as an ingredient that is initially introduced into interstate commerce after December 1, 1975, that is not in compliance with this section is subject to regulatory action.

A skin irritant.

To investigate the possible participation of oxygen intermediates (OIs) in the contact photosensitization process, mice were treated with long-acting liposomal-superoxide dismutase (L-SOD) before photosensitization. Photosensitization to 3,3',4',5-tetrachlorosalicylanilide (TCSA) was significantly suppressed by the pretreatment of mice with L-SOD. This suppression was not mediated by suppressor cells or due to an unresponsive state produced by the use of L-SOD. Rather, the suppression appeared to be due to the failure of production of photoallergen. L-SOD treatment induced the suppression of contact photosensitivity to TCSA but not ordinary contact sensitivity to TCSA or dinitrofluorobenzene, suggesting that the production of photoallergen is more critically dependent on the presence of OIs than that of ordinary contact allergen. The results provide evidence that OIs are produced by light absorption in the presence of oxygen and react with the biologic substrate to form photoallergens.|A marked contact photosensitivity (CPS) response to 3,3',4',5 tetrachlorosalicylanilide (TCSA) plus UVA was induced in mice. Cyclophosphamide (Cy), given prior to sensitization, caused a further increase in ear swelling. When UVB radiation was given at a site distant from that used for sensitization it caused a dose-related suppression of CPS. Cy did not eliminate the UVB-induced suppression.|An animal model /was developed/ to assess the ultraviolet A (UVA) protective effect of topical sunscreens with the use of BALB/cJ mice in which contact photosensitivity to 3, 3', 4', 5 tetrachlorosalicylanilide had been induced. The mice were sensitized on the clipped dorsal skin and challenged on the ears. Changes in ear thickness after challenge were used to measure the degree of photosensitivity. The efficacy of two doses of each topical sunscreen was assessed by the degree of suppression of the contact photosensitivity response at challenge. Control studies were performed with the base of each sunscreen. Some but not all sunscreens that contained UVA-absorbing chemicals showed active suppression of contact photosensitivity in this test system. Several sunscreens gave greater suppression at 5 uL/sq cm than at 2 uL/sq cm, which suggests a dose-related effect. One sunscreen, however, gave greater suppression at 2 uL/sq cm. Several of the bases tested also suppressed the contact photosensitivity response. An unexpected finding was an enhancement of the contact photosensitivity reaction by two of the bases tested.|This study was conducted to investigate in vivo evaluation of protectiveness by sunscreens in the UVA range using a mouse model of contact photoallergy (CPS) to 3,3',4',5-tetrachlorosalicylanilide (TCSA). Mice were sensitized with TCSA painting plus UVA irradiation (TCSA/UVA) on the abdomen and, 5 days later, challenged with TCSA/UVA on the earlobe. Each of four sunscreen agents, benzophenone-3, Parsol 1789, p-aminobenzoic acid, and 2-ethyl-hexyl-p-methoxycinnamate, was applied to the earlobes before irradiation. Their protective efficacy was evaluated in the degree of inhibition of both ear swelling responses and TCSA-epidermal cell photoadduct formation. Two UVA-absorbing sunscreens, benzophenone-3 and Parsol 1789, dramatically inhibited the ear swelling response, while the two UVB-absorbers exhibited a much less suppressive effect. The UVA-absorbing agents functioned via inhibiting the formation of TCSA-epidermal cell photoadducts.

LD50 Rat oral 243 mg/kg

3,3',4',5-Tetrachlorosalicylanilide's production and use as a preservative in textile finishes, certain petroleum products, cellulose esters, cutting oils, and coolants(1) may result in its release to the environment through various waste streams. Its former use as a bacteriostat in a number of drug products(2) may have resulted in its release to the environment through various waste streams. I

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 4100(SRC), determined from a structure estimation method(2), indicates that 3,3',4',5-tetrachlorosalicylanilide is expected to have slight mobility in soil(SRC). The pKa of 3,3',4'5-tetrachlorosalicylanilide is 6.8(3), indicating that this compound will partially exist in 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). Volatilization of 3,3',4',5-tetrachlorosalicylanilide from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 4.8X10-11 atm-cu m/mole(SRC), using a fragment constant estimation method(5). 3,3',4',5-Tetrachlorosalicylanilide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-10 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation data were not available(SRC, 2009).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 4100(SRC), determined from a structure estimation method(2), indicates that 3,3',4',5-tetrachlorosalicylanilide is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 4.8X10-11 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3500(SRC), from an estimated log Kow of 5.87(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC). 3,3',4',5-Tetrachlorosalicylanilide is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(8). Biodegradation data were not available(SRC, 2009).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 3,3',4',5-tetrachlorosalicylanilide, which has an estimated vapor pressure of 3.0X10-10 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase. Particulate-phase 3,3',4',5-tetrachlorosalicylanilide may be removed from the air by wet or dry deposition(SRC). 3,3',4',5-Tetrachlorosalicylanilide contains chromophores that absorb at wavelengths >290 nm(3) and therefore may be susceptible to direct photolysis by sunlight(SRC).

3,3',4',5-Tetrachlorosalicylanilide is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). 3,3',4',5-Tetrachlorosalicylanilide contains chromophores that absorb at wavelengths >290 nm(1) and therefore may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3500 was calculated in fish for 3,3',4',5-tetrachlorosalicylanilide(SRC), using an estimated log Kow of 5.87(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 3,3',4',5-tetrachlorosalicylanilide can be estimated to be 4100(SRC). According to a classification scheme(2), this estimated Koc value suggests that 3,3',4',5-tetrachlorosalicylanilide is expected to have slight mobility in soil. The pKa of 3,3',4',5-Tetrachlorosalicylanilide is 6.8(3), indicating that this compound will partially exist in 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 Henry's Law constant for 3,3',4',5-tetrachlorosalicylanilide is estimated as 4.8X10-11 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that 3,3',4',5-tetrachlorosalicylanilide is expected to be essentially nonvolatile from water surfaces(2). 3,3',4',5-Tetrachlorosalicylanilide is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.0X10-10 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to 3,3',4',5-tetrachlorosalicylanilide may occur through dermal contact with this compound at workplaces where 3,3',4',5-tetrachlorosalicylanilide is produced or used. Use data indicate that the general population may be exposed to 3,3',4',5-tetrachlorosalicylanilide via dermal contact with consumer products containing 3,3',4',5-tetrachlorosalicylanilide. (SRC)

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. (See all compounds classified as Enzyme Inhibitors.)

Effects of 3,3',4',5-tetrachlorosalicylanilide (TCS), a lipophilic weak acid, on Ca2+ uptake and ATP hydrolysis by the sarcoplasmic reticulum calcium pump were characterized to obtain insight into the possible role of hydrophobic portions of the Ca2+-ATPase in the catalytic mechanism of the enzyme. TCS exhibited both the stimulatory and inhibitory effects on the calcium pump activities depending on its concentration. At optimal concentrations, it increased these activities by up to 5-fold at pH 7.0 and 6 °C. Analysis of partial reactions of ATP hydrolysis by the purified ATPase revealed that TCS accelerated Ca2+ release from the ADP-sensitive phosphoenzyme up to 6- fold, whereas it affected other reaction steps to a much less extent, indicating that the site of the stimulatory action of TCS is rather specific in terms of the reaction sequence. These effects of TCS became less prominent at higher temperatures, although the enzyme-TCS interactions as detected in the direct binding experiment or by measurement of quenching of protein fluorescence were not affected by a similar change in temperature. The TCS effects were also dependent on pH of the 8.0 suggested that the protonated form of TCS is responsible for both the stimulatory and inhibitory effects of the drug. These results, taken together with those obtained previously with a spin- labeled probe, may suggest that TCS stimulates the calcium pump activity through its effect on the lipid bilayer, although its direct action on hydrophobic portion(s) of the ATPase protein cannot be ruled out.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ The photomaximization procedure was designed to identify topical photocontact sensitizers following the format of the maximization test for contact sensitizers. The test agent is applied for 24 hours followed by exposure to three Minimal Erythema Doses (MED) of solar simulated radiation twice weekly for 3 weeks (six exposures) in a panel of 25 white Caucasoids. The subjects are challenged 2 weeks later with 4.0 J/sq cm of long-wave ultraviolet radiation (UV-A). Photocontact sensitization was induced to 3,3'4',5-tetrachlorosalicylanilide (TCSA) ... .

3,3',4',5-tetrachlorosalicylanilide

Benzamide, 3,5-dichloro-N-(3,4-dichlorophenyl)-2-hydroxy-: INACTIVE|Use in food, drugs, and cosmetics may be restricted|The halogenated salicylanilide 3,3',4',5-tetrachlorosalicylanilide... was found to be a potent photosensitizer capable of causing disabling skin disorders. FDA directed the removal from the market of drug products containing 3,3',4',5-tetrachlorosalicylanilide in 1975.|Halogenated salicylanilides ... 3,3',4,',5-tetrachlorosalicylanilide ... have been used as antimicrobial agents for a variety of purposes in cosmetic products. These halogenated salicylanilides are potent photosensitizers and cross-sensitizers and can cause disabling skin disorders... Safer alternative antimicrobial agents are available... any cosmetic product that contains such a halogenated salicylanilide as an ingredient at any level for any purpose is deemed to be adulterated under section 601(a) of the Federal Food, Drug, and Cosmetic Act. Any cosmetic product containing these halogenated salicylanilides as an ingredient that is initially introduced into interstate commerce after December 1, 1975, that is not in compliance with this section is subject to regulatory action.