An evaluation of the aquatic hazard of cumene (isopropyl benzene).

Cumene manufacturers were required under a TSCA Section 4(a) test rule to evaluate the aquatic toxicity of cumene to daphnids, rainbow trout, mysid shrimp, and sheepshead minnows. Because of cumene's high volatility (vapor pressure, 3.2 mm Hg at 20 degrees C), all tests were conducted under flowthrough conditions using a proportional diluter system. The 96-hr LC50s for rainbow trout, sheepshead minnow, and mysid shrimp, based on mean measured concentrations, were 4.8, 4.7, and 1.3 mg/liter, respectively. The 48-hr daphnid EC50 was 4.0 mg/liter. Although cumene is considered moderately toxic to aquatic organisms under rigorous laboratory conditions, its volatility and biodegradability greatly reduce its hazard to the aquatic environment.

Evaluation of the relationship between PAH content and mutagenic activity of fumes from roofing and paving asphalts and coal tar pitch.

Fume condensates from asphalt and coal tar pitch were evaluated to determine if polycyclic aromatic hydrocarbon (PAH) composition, crude oil source, or temperature at which the fume was generated correlated with mutagenic activity. The fume condensates were tested for mutagenic activity using a modified Ames Test. Benzo[a]pyrene (BP) and other PAHs were detected in all samples. The concentration of BP in coal tar pitch was 18,100 ppm while the concentration in asphalt was less than 6 ppm. Coal tar fumes contained between two and three orders of magnitude more BP, as well as other PAH species, than asphalt fumes. Coal tar fume condensates were also approximately 100 times more mutagenic than those of asphalt. Generation temperature, crude oil source, and/or process conditions affected the PAH concentrations but not the mutagenicity in roofing asphalt fume condensates. With paving asphalt fumes, PAH content and mutagenicity varied with crude oil source but not with processing conditions; due to limited data, it was not possible to determine the effect of generation temperature. Coal tar pitch fumes generated at 316 degrees C contained significantly higher concentrations of PAHs than those generated at 232 degrees C and the mutagenic activity generally paralleled the PAH content. A subset of the paving asphalts demonstrated good correlation between mutagenicity and three- to seven-ring PAH content. These results indicate that asphalt fumes are far less mutagenic than coal tar fumes. Asphalt fumes differ in their ability to induce mutagenic activity, and, most likely, in their potential carcinogenicity.

Profenofos insecticide bioactivation in relation to antidote action and the stereospecificity of acetylcholinesterase inhibition, reactivation, and aging.

Poisoning signs in chicks administered the organophosphorus insecticide profenofos correlated with in vivo inhibition of brain acetylcholinesterase (AChE) activity. Mixtures of atropine with eserine, pyridinium oximes, or the bispyridinium compound SAD-128 increased the LD50 of coadministered profenofos by up to sevenfold in chicks and fourfold in mice. Atropine and the oximes were less effective as profenofos antidotes, indicating that profenofos-inhibited AChE may undergo rapid aging. Brain AChE from chicks poisoned with profenofos was not reactivated by pralidoxime methanesulfonate, although it was from chicks poisoned with the phosphoramidothiolate, methamidophos. Similarly, eel AChE, inhibited in vitro by bioactivated (-)-profenofos, the most toxic isomer, did not reactivate in contrast to that inhibited by methamidophos, nonbioactivated (-)-profenofos, and (+)-profenofos, with or without bioactivation. It appears that the action of eserine and possibly SAD-128 was due to protecting AChE or cholinergic receptors from profenofos or bioactivated profenofos and that oximes may work in the same way rather than as reactivators due to rapid aging of the inhibited AChE.

Oxidative bioactivation of S-alkyl phosphorothiolate pesticides: stereospecificity of profenofos insecticide activation.

The mouse liver microsomal mixed-function oxidase system converts several phosphorothiolate pesticides with S-ethyl, S-propyl, or S-butyl groups to more potent inhibitors of acetylcholinesterase. This activation is stereospecific for the chiral isomers of O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothiolate (profenofos insecticide); the more toxic (-) isomer becomes a 34-fold better inhibitor of acetylcholinesterase in vitro, whereas the less toxic (+) isomer is deactivated by a factor of 2. Prior treatment of the microsomes with piperonyl butoxide or another mixed-function oxidase inhibitor markedly decreases the activation. Piperonyl butoxide also protects against brain acetylcholinesterase inhibition and cholinergic symptoms in chicks resulting from (-)-profenofos administration, thus establishing the importance of the oxidative bioactivation of S-alkyl phosphorothiolate pesticides in vivo.

Species and structural variations affecting pyrethroid neurotoxicity.

Pyrethroids provide fascinating patterns and examples of species selectivity resulting from variations in nerve sensitivity and detoxification rates. Three classification systems are useful in considering pyrethroids: origin, structure, stability and use relative to the natural pyrethrin I; lethal and sublethal or knockdown agents; Types I and II symptoms and nerve action. Pyrethroid-detoxifying esterases and oxidases contribute importantly to the species and strain specificity and provide an opportunity to use inhibitors as synergists for improved effectiveness. Pyrethroids are potent and selective neuropharmacological agents inducing repetitive discharges or conduction block in a variety of sensory and motor nerves and in the CNS. Small structural modifications in the pyrethroid often change the type of action as well as the potency and species specificity. Pyrethroid resistance in selected strains of insect pests may involve a modified and pyrethroid-insensitive target site.