Cholinesterase inhibitors reproductive toxicity

DOT CLASSIFICATION 6.1 Label Poison SAFETY PROFILE Poison by inhalation, ingestion, skin contact, subcutaneous, intravenous, and intraperitoneal routes. Fatal poisoning can result from skin or eye contact after very brief exposure to concentrated solution. Experimental teratogenic and reproductive effects. Questionable carcinogen. Human mutation data reported. A cholinesterase inhibitor type of insecticide. When heated to decomposition it emits very toxic fumes of NOx, POx, and SOx. See also PARATHION. 

A highly toxic substance by ingestion, and possibly by most other routes of exposure moderately toxic by inhalation and skin contact cholinesterase inhibitor toxic effects are similar to those of other carbamate pesticides and include excessive salivation, lacrimation, slow heart rate, blurred vision, twitching of muscle and lack of coordination, nausea, weakness, diarrhea and abdominal pain oral intake of probably 1.5-3 g could be fatal to adult humans a teratogenic substance, producing adverse reproductive effects in experimental animals. 

Agent GA (Tabun). RfDe = 4 x 10 mg kg d" . A NOAEL was identified in a 90-d study in rats. A total uncertainty factor of 3000 was applied to account for protection of sensitive subpopulations (10), animal-to-human extrapolation (10), extrapolation from a subchronic to chronic exposure (3), and incomplete data base (3). An uncertainty factor of 3 was used to extrapolate from a subchronic to chronic exposure because of the unlikelihood that the LOAEL would have been substantially lower if the exposure had been chronic. A LOAEL-to-NOAEL uncertainty factor was not needed because a NOAEL was used in the derivation. The data base for GA lacks a multigeneration reproductive toxicity study, but because the available evidence indicates that organophosphate cholinesterase inhibitors such as GA are not likely to be reproductive toxins, the missing study was not considered critical. Therefore, a UFd of 3, not the default value of 10, was applied. A Modifying Factor of 3 was applied because the key study involved a nonoral exposure route (intraperitoneal injections). 

LD50 (oral, male rat) 80 mg/kg, (IP, mouse) 22 mg/kg, (subcut., mouse) 24 mg/kg, (skin, rabbit) 107 mg/kg poison by ing., inh., subcut., IV, IP routes toxic by skin absorption cholinesterase inhibitor very rapidly metabolized and excreted confirmed carcinogen tumorigen experimental teratogen, reproductive effects human mutagenic data TSCA listed... 

Properties Colorless clear vise, liq. mild odor sol. in most org. soivs., 95% ethanol, acetone, DMSO, ketones, chlorinated hydrocarbons sol. < 1 mg/ml in water insol. in aliphatic hydrocarbons m.w. 430.91 dens. 1.508 g/cm (22.2 C) vapor pressure 10.3 mm Hg (25 C) f.p. 27 C b.p. 236-237 C (5 mm) flash pt. 252 C ref. index 1.5022 Toxicology LD50 (oral, rat) 1850 mg/kg, (skin, rabbit) > 23,700 mg/kg mod. toxic by ing. may cause irritation of skin, respiratory tract cholinesterase inhibitor may cause tremors, convulsions, irritability, hypermotility, diarrhea, enzyme inhibition, change in blood/tissue levels, changes in liver/kidney wt questionable carcinogen experimental teratogen and reproductive effects mutagenic data ... 

Toxicology LD50 (oral, rat) 1311 mg/kg, (dermal, guinea pig) > 20 mi/kg LDLo (orai, rat) 1600 mg/kg mod. toxic by ing., iP, iV routes causes eye irritation may cause nerve damage cholinesterase inhibitor experimental reproductive effects mutagenic data TSCA listed... 

Several classes of pesticides and other chemicals are of particular concern as water pollutants because of their potential effects. These are (1) highly biodegradation-resistant compounds, (2) known or probable carcinogens, (3) toxicants with adverse reproductive or developmental effects, (4) neurotoxins inclnding cholinesterase inhibitors, (5) substances with high acute toxicities, (6) known groundwater contaminants. Table 4.5 lists some of the most commonly used pesticides that may be of concern as water poUntants. 

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