Zinc Pyrithione

Zinc Pyrithione is an antifungal and antibacterial agent disrupting membrane transport by blocking the proton pump.Target: Proton PumpZinc pyrithione is considered as a coordination complex of zinc. The pyrithione ligands, which are formally monoanions, are chelated to Zn 2+ via oxygen and sulfur centers. In the crystalline state, zinc pyrithione exists as a centrosymmetric dimer, where each zinc is bonded to two sulfur and three oxygen centers. In solution, however, the dimers dissociate via scission of one Zn-O bond. Zinc pyrithione, which is a dimer but is probably biologically active as a monomer, induces plasma membrane depolarization with half-maximal effect (K1/2) of about 0.3 mM [1]. Zinc pyrithione is an unusual synthetic potentiator that potently activates both heterologous and native M channels by inducing channel opening at the resting potential [2]. Zinc pyrithione rapidly accumulated in the tissues of the exposed mussels, proportionately to both exposure concentration and time. Even though the 7-d median lethal concentration (LC50) = 8.27 μM established here appears high with respect to reported ZnPT environmental concentrations, the results indicate that this biocide could represent a threat for marine organisms in coastal environments and that further investigations on its biological effects at sublethal doses are needed [3].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Proton Pump

Research Areas >> Cardiovascular Disease

[1]. Ermolayeva, E. and D. Sanders, Mechanism of pyrithione-induced membrane depolarization in Neurospora crassa. Appl Environ Microbiol, 1995. 61(9): p. 3385-90.

[2]. Xiong, Q., H. Sun, and M. Li, Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels rescues epileptogenic mutants. Nat Chem Biol, 2007. 3(5): p. 287-96.

[3]. Marcheselli, M., C. Rustichelli, and M. Mauri, Novel antifouling agent zinc pyrithione: determination, acute toxicity, and bioaccumulation in marine mussels (Mytilus galloprovincialis). Environ Toxicol Chem, 2010. 29(11): p. 2583-92.

Bafilomycin A1 | omeprazole | Vonoprazan Fumarate (TAK-438) | Lansoprazole | Ilaprazole | AZD0865 | Soraprazan | bamaquimast | Esomeprazole | Esomeprazole magnesium | Chebulinic acid | Picoprazole | SKF96067 | Pumaprazole | S3337

MOLECULAR FORMULA :

C10-H8-N2-O2-S2-Zn

MOLECULAR WEIGHT :

317.69

WISWESSER LINE NOTATION :

T6NJ AO BS-ZN-S- BT6NJ AO

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

Standard Draize test

ROUTE OF EXPOSURE :

Administration into the eye

SPECIES OBSERVED :

Rodent - rabbit

REFERENCE :

JANCA2 Journal of the Association of Official Analytical Chemists. (Assoc. of Official Analytical Chemists, 1111 N. 19th St., Suite 210, Arlington, VA 22209) V.49- 1966- Volume(issue)/page/year: 56,905,1973 ** ACUTE TOXICITY DATA **

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

177 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TOANDB Toxicology Annual. (New York, NY) 1974/75-79. Discontinued. Volume(issue)/page/year: 3,1,1979

TYPE OF TEST :

LC50 - Lethal concentration, 50 percent kill

ROUTE OF EXPOSURE :

Inhalation

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

140 mg/m3/4H

TOXIC EFFECTS :

Lungs, Thorax, or Respiration - acute pulmonary edema Lungs, Thorax, or Respiration - dyspnea Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

NTIS** National Technical Information Service. (Springfield, VA 22161) Formerly U.S. Clearinghouse for Scientific & Technical Information. Volume(issue)/page/year: OTS0527753-1

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

160 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 13,1,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

26800 ug/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 8,1067,1974

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

730 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 13,1,1978

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

600 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

CTOXAO Clinical Toxicology. (New York, NY) V.1-18, 1968-81. For publisher information, see JTCTDW. Volume(issue)/page/year: 13,1,1978

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

25 mg/kg

TOXIC EFFECTS :

Brain and Coverings - recordings from specific areas of CNS Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - somnolence (general depressed activity)

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 9,269,1966

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

25 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - effect, not otherwise specified

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 9,269,1966

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YKYUA6 Yakkyoku. Pharmacy. (Nanzando, 4-1-11, Yushima, Bunkyo-ku, Tokyo, Japan) V.1- 1950- Volume(issue)/page/year: 32,965,1981

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

10 mg/kg

TOXIC EFFECTS :

Behavioral - changes in motor activity (specific assay)

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 9,269,1966

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

>2 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 7,425,1965

TYPE OF TEST :

LC50 - Lethal concentration, 50 percent kill

ROUTE OF EXPOSURE :

Inhalation

SPECIES OBSERVED :

Mammal - species unspecified

DOSE/DURATION :

140 mg/m3/4H

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

EPASR* United States Environmental Protection Agency, Office of Pesticides and Toxic Substances. (U.S. Environmental Protection Agency, 401 M St., SW, Washington, DC 20460) History unknown. Volume(issue)/page/year: 8EHQ-0790-1035 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

42 mg/kg/14D-C

TOXIC EFFECTS :

Peripheral Nerve and Sensation - recording from peripheral motor nerve Behavioral - muscle weakness Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :

NETEEC Neurotoxicology and Teratology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.9- 1987- Volume(issue)/page/year: 12,153,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Administration onto the skin

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

300 mg/kg/15D-I

TOXIC EFFECTS :

Peripheral Nerve and Sensation - spastic paralysis with or without sensory change Related to Chronic Data - death

REFERENCE :

50TXAR "Cutaneous Toxicity, base on Papers presented at the Conference on Cutaneous Toxictiy, 5th, New York, May 6-18, 1982," Drill, V.A. and P. Lazar eds. Raven Press 1984 Volume(issue)/page/year: 5,109,1984

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

350 mg/kg/14D-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - retinal changes (pigmentary depositions, retinitis, other) Sense Organs and Special Senses (Eye) - effect, not otherwise specified Related to Chronic Data - death

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 45,771,1978

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Primate - monkey

DOSE/DURATION :

840 mg/kg/28D-I

TOXIC EFFECTS :

Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea Related to Chronic Data - death

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 45,771,1978

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

100 mg/kg/8D-I

TOXIC EFFECTS :

Sense Organs and Special Senses (Eye) - effect, not otherwise specified

REFERENCE :

TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 45,771,1978 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

150 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 17,639,1979

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Administration onto the skin

DOSE :

75 mg/kg

SEX/DURATION :

female 6-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - Central Nervous System Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 17,639,1979

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Administration onto the skin

DOSE :

1065 mg/kg

SEX/DURATION :

female 8 week(s) pre-mating female 1-15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 17,639,1979

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

65 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 17,639,1979

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Administration onto the skin

DOSE :

1300 mg/kg

SEX/DURATION :

female 6-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetal death

REFERENCE :

FCTXAV Food and Cosmetics Toxicology. (London, UK) V.1-19, 1963-81. For publisher information, see FCTOD7. Volume(issue)/page/year: 17,639,1979 *** U.S. STANDARDS AND REGULATIONS *** EPA FIFRA 1988 PESTICIDE SUBJECT TO REGISTRATION OR RE-REGISTRATION FEREAC Federal Register. (U.S. Government Printing Office, Supt. of Documents, Washington, DC 20402) V.1- 1936- Volume(issue)/page/year: 54,7740,1989 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 83016 No. of Facilities: 43 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 387 (estimated)