3,3',4',5-테트라클로로살리실아닐라이드

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.

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.

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).

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).

/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'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

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).

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).

/ALTERNATIVE and IN VITRO TESTS/... An in vitro immune lymph node cell (LNC) proliferation system /was used to investigate/ the mechanism of induction and elicitation of contact photosensitivity (CPS) by 3,3',4',5-tetrachlorosalicylanilide (TCSA) painting plus UVA irradiation. The proliferation of LNC from TCSA-photosensitized mice was not augmented by the addition of TCSA-photocoupled syngeneic spleen cells (SC) or epidermal cells (EC), whereas the picryl chloride immune LNC proliferation was activated by trinitrophenyl-coupled (TNP-coupled) SC or EC. While the viability of SC and EC was unchanged even after TNP haptenization, cells showed very low levels of viability after TCSA photohaptenization. This suggests that the inability of photoTCSA-modified cells to activate LNC proliferation is because of their low viability. Nylon wool column purified lymph node T cells from TCSA-photosensitized mice were activated by photohapten-conjugated SC or photohaptenized EC fragments only in the presence of peritoneal macrophages (M phi). The function of live M phi was not replaced by interleukin-1 (IL-1), suggesting that M phi were required for processing and/or presentation of photohapten rather than simply providing IL-1. ...

/IMMUNOTOXICITY/ Induction in mice of marked photoallergic contact dermatitis (PCD) to 3,3',4',5-tetrachlorosalicylanilide (TCSA) with UVA (320 to 400 nm) radiation requires pretreatment with cyclophosphamide (CY). Attempts to induce photoallergic contact dermatitis without CY result in only a small degree of sensitivity, accompanied by significant net splenic suppressor cell activity. These suppressor cells are antigen specific, inhibit the induction but not the elicitation of photoallergic contact dermatitis to TCSA, and are T lymphocytes. Exposure of mice to UVB (280 to 320 nm) radiation at a site distant from that of sensitization, before CY administration and sensitization, inhibits the development of photoallergic contact dermatitis. This is analogous to the suppression of allergic contact dermatitis (ACD) observed in mice after exposure to UVB radiation; such suppression is accompanied by the formation of antigen-specific splenic suppressor cells. However, in contrast to the findings with allergic contact dermatitis, splenic suppressor cells are not detected in mice that are treated with UVB radiation before CY administration and sensitization to TCSA. This is presumably because CY prevents their formation. This provides evidence that UVB-irradiated mice have a second form of anergy that is not mediated by suppressor cells.

/IMMUNOTOXICITY/ Allergic photocontact sensitization could be induced in guinea pigs with 3,3',4',5-tetrachlorosalicylanilide (TCSA), 3,4',5-tribromosalicylanilide (TBS), and bithionol using pretreatment with sodium lauryl sulfate (SLS) and long-wave ultraviolet (UVA) radiation. Mid-wave ultraviolet below 320 nm (UVB) was not necessary for the induction of sensitization. Combined use of SLS pretreatment with UVA radiation resulted in more effective sensitization than combined UVB and UVA radiation. Higher sensitization rates to TCSA and TBS were achieved by allowing rest periods between each of 5 2-hr exposures to UVA than by daily 1-hr exposures for 10 consecutive days. The opposite result was obtained with bithionol. Although UVB has been customarily used in the past for induction of photosensitivity, its role is only to irritate the site of induction.

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).

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)

3,3',4',5-Tetrachlorosalicylanilide's production and use as a preservative in textile finishes, certain petroleum products, cellulose esters, cutting oils, and coolants may result in its release to the environment through various waste streams. Its former use as a bacteriostat in a number of drug products may have resulted in its release to the environment through various waste streams. If released to air, an estimated vapor pressure of 3.0X10-10 mm Hg at 25 °C indicates 3,3',4',5-tetrachlorosalicylanilide will exist solely in the particulate phase in the atmosphere. Particulate-phase 3,3',4',5-tetrachlorosalicylanilide will be removed from the atmosphere by wet or dry deposition. 3,3',4',5-Tetrachlorosalicylanilide contains chromophores that absorb at wavelengths >290 nm and therefore may be susceptible to direct photolysis by sunlight. If released to soil, 3,3',4',5-tetrachlorosalicylanilide is expected to have slight mobility based upon an estimated Koc of 4100. The estimated pKa of 3,3',4'5-tetrachlorosalicylanilide is 6.8, 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. Volatilization from moist soil surfaces is not expected to be an important fate process based upon an estimated Henry's Law constant of 4.8X10-11 atm-cu m/mole. Biodegradation data were not available. If released into water, 3,3',4',5-tetrachlorosalicylanilide is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Volatilization from water surfaces is not expected to be an important fate process based upon this compound's estimated Henry's Law constant. An estimated BCF of 3500 suggests the potential for bioconcentration in aquatic organisms is very high, provided the compound is not metabolized by the organism. 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 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 this compound. (SRC)

/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/

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.