Search PubMed⌕ Search

Biomedical subjects

R L Metcalf

Publications and source records attributed to R L Metcalf.

At least 19 recordsLinked to original sources
PubMed1985

Toxicity of organophosphorus esters to laying hens after oral and dermal administration.

Fourteen organophosphorus esters (OPs) were evaluated for their potential to cause organophosphorus ester induced delayed neurotoxicity (OPIDN) when administered dermally and/or orally to white leghorn hens. The compounds were chlorpyrifos, DEF, dichlorvos, dimethoate, EPN, ethoprop, fenthion, isofenphos, leptophos, merphos, ronnel, tetrachlorvinphos, terbufos, and trichlorfon. DEF induced ataxia if given dermally or orally at over 21 mg/kg/day for up to 90 days. Hens treated with EPN developed irreversible ataxia after repeated exposure to as little as 1.3 mg/kg dermally or 5 mg/kg/day orally, while leptophos was neurotoxic at doses of 6-7 mg/kg/day dermally and 10 mg/kg/day orally. Multiple treatments of chlorpyrifos, terbufos, dichlorvos and dimethoate caused death after varying periods of increasing debility; although birds had difficulty walking, they did not display typical symptoms of OPIDN. Fenthion and isofenphos induced drastic weight loss in hens at low levels of treatment; Isofenphos treated hens developed OPIDN, but died soon afterwards. Dichlorvos given at greater than 6 mg/kg/day po or dermally at 1 mg/kg/day produced cholinergic symptoms and most hens died before the end of the treatment period. At lower levels, dichlorvos did not induce overt ataxia. None of the other compounds in this series induced consistent ataxia whether administered orally or dermally. Ethoprop, with an acute oral LD50 near 5 mg/kg and an acute dermal LD50 of approximately 3 mg/kg, was the most toxic compound tested and could not be fully evaluated for its potential to cause OPIDN.

Administration, Oral↗
PubMed1985

Neurotoxicity of diallate and triallate when administered orally or topically to hens.

Two allylthiocarbamate herbicides, diallate and triallate, were evaluated for neurotoxicity by oral and topical dosing studies with mature white leghorn hens. Diallate was tolerated for 90 days at topical doses of 40 mg/kg/day and oral doses of 20 mg/kg/day. Reversible ataxia and narcosis occurred at diallate doses of 80 mg/kg/day and higher by either route of administration. Triallate did not elicit signs of neurotoxicity at 300 mg/kg/day topically or 400 mg/kg/day orally. The oral dose, however, resulted in gastrointestinal irritation and severe weight loss, such that dosing was terminated after 25 days. Triallate was tolerated at oral dosages of 90 mg/kg/day and topical doses up to 330 mg/kg/day.

Administration, Oral↗
PubMed1984

Evaluation of mirex, photomirex and chlordecone in the terrestrial aquatic laboratory model ecosystem.

The insecticides mirex and chlordecone and the mirex photodegradation product, photomirex, were evaluated in a terrestrial aquatic laboratory model ecosystem. Although chlordecone was to some extent degraded during the 33 days, neither mirex nor photomirex produced identifiable levels of decomposition products in the water or in any of the organisms of the model ecosystem. All three compounds accumulated significantly in the organisms of the model ecosystem, with chlordecone the least bioaccumulative and photomirex the most bioaccumulative.

Animals↗
PubMed1983

In vitro neurotoxic esterase assay using leptophos oxon analogs as inhibitors.

In comparing neurotoxic esterase (NTE) inhibition properties of a series of phenylphosphonates, it was discovered that certain compounds including leptophos inhibited mipafox-insensitive phenylvalerate hydrolases. This leads to erroneous values for NTE inhibition which can be corrected by a differential assay: the total amount of mipafox-insensitive activity is determined with O-(2,6-dichlorophenyl)O-methyl phenylphosphonate and subtracted from the apparent NTE determined with the test compound before calculating pI50's.

Animals↗
PubMed1982

Comparison of the delayed neurotoxicity of O-methyl and O-ethyl analogs of EPN, leptophos, and cyanofenphos.

Eight pairs of O-methyl and O-ethyl O-(substituted-phenyl) phenylphosphonothionates were evaluated with respect to their delayed neurotoxic activity in hens. O-methyl compounds were in all cases more active than their O-ethyl analogs. The neurotoxic potential of the O-methyl phenylphosphonothionates was 2,5-diCl greater than 4-NO2 greater than 2,4,5-triCl and 2,4,6-triCl greater than 2,4-diCl greater than 2,5-diCl-4-Br greater than 4-CN, when single oral doses were given. Both EPN-ethyl and leptophos-methyl were more neurotoxic in multiple dermal than multiple oral dosing regimens. LD50s for mice and flies were established.

Administration, Oral↗
PubMed1980

Neurotoxicity of halogenated O-phenyl O-alkyl alkylphosphonothioates.

Twenty-seven halogenated organophosphorus esters were tested for neurotoxicity in adult hens. Fourteen compounds were overtly neurotoxic, including eight of the eleven methylphosphonothioates, three of seven ethylphosphonothioates, and three of six phosphoramidates, one of which was the commercial herbicide DMPA. Neurotoxic activity varied both with the number of halogen substituents on the phenyl group, and with the identity of the 4-phenyl halogen. Neurotoxic activity also varied with the alkyl group involved in the P-C or P-N bond, and with the identity of the O-alkyl group.

Animals↗
PubMed1980

Ecotoxicology of phenylphosphonothioates.

The phenylphosphonothioate insecticides EPN and leptophos, and several analogs, were evaluated with respect to their delayed neurotoxic effects in hens and their environmental behavior in a terrestrial-aquatic model ecosystem. Acute toxicity to insects was highly correlated with sigma sigma of the substituted phenyl group (regression coefficient r = -0.91) while acute toxicity to mammals was slightly less well correlated (regression coefficient r = -0.71), and neurotoxicity was poorly correlated with sigma sigma (regression coefficient r = -0.35). Both EPN and leptophos were markedly more persistent and bioaccumulative in the model ecosystem than parathion. Desbromoleptophos, a contaminant and metabolite of leptophos, was seen to be a highly stable and persistent terminal residue of leptophos.

Animals↗
PubMed1977

The Environmental fate of three carcinogens: benzo-(alpha)-pyrene, benzidine, and vinyl chloride evaluated in laboratory model ecosystems.

Radiolabeled benzo-((alpha)-pyrene, benzidine, and vinyl chloride were evaluated in laboratory model ecosystems for environmental fate, degradation pathways, bioconcentration, and food chain accumulation. The comparative effects of microsomal detoxications were evaluated using the inhibitor piperonyl butoxide. The accumulation and bioconcentration of benzo-(alpha)-pyrene and benzidine were closely correlated with their octanol/water partition coefficients and water solubility. Benzo-(alpha)-pyrene as predicted by these parameters was bioaccumulated to substantial levels in several organisms. Vinyl chloride was not accumulated because of its high volatility.

Animals↗
PubMed1977

Tissue distribution of PCB components in swine and sheep fed three different rations containing Aroclors 1242 and 1254.

Growing swine and sheep were fed three dietary variations containing 20 ppm of Aroclors 1242 or 1254 for 13 to 15 weeks. Generally, Aroclor 1254 residues were higher; higher 1242 residues in swine blood, spleen, and ovary are attributed to persistent major components of this Aroclors. Some minor differences in total PCB were observed with varying diets, but peak composition did not vary. Some lower chlorinated components maintained higher levels in the blood relative to other components; other components were selectively accumulated in tissues such as fat and muscle. Blood and fat residues in sheep declined during the last weeks of feeding. Microsomal oxidase levels were elevated in response to PCB and diet in both species, but the response was greater in sheep. Sheep liver microsomes were capable of metabolizing pure analogs and components of Aroclor 1242. Major differences in Aroclor profiles can be demonstrated between swine and sheep residues and total residues can be estimated by measuring selected peaks in blood and backfat. The peaks which provide the most reliable estimate of total PCB residue vary with species and Aroclor.

Animal Feed↗
PubMed1976

Model ecosystem evaluation of the environmental impacts of the veterinary drugs phenothiazine, sulfamethazine, clopidol, and diethylstilbestrol.

Four veterinary drugs of dissimilar chemical structures were evaluated for environmental stability and penchant for bioaccumulation. The techniques used were (1) a model aquatic ecosystem (3 days) and (2) a model feedlot ecosystem (33 days) in which the drugs were introduced via the excreta of chicks or mice. The model feedlot ecosystem was supported by metabolism cage studies to determine the amount and the form of the drug excreted by the chicks or mice. Considerable quantities of all the drugs were excreted intact or as environmentally short-lived conjugates. Diethylstilbestrol (DES) and Clopidol were the most persistent molecules, but only DES bioaccumulated to any appreciable degree. Phenothiazine was very biodegradable; sulfamethazine was relatively biodegradable and only accumulated in the organisms to very low levels. Data from the aquatic model ecosystem demonstrated a good correlation between the partition coefficients of the drugs and their accumulation in the fish.

Animals↗
PubMed1976

Effects of feeding polychlorinated biphenyls to broiler cockerels in three dietary regimes.

Polychlorinated biphenyls (Aroclor 1242 and 1254) were fed at 20 p.p.m. to hybrid broiler cockerels between one and nine weeks of age in three dietary variations. The Aroclors did not affect growth or feed efficiency and no consistent histopathological lesions could be attributed to them. There was a low incidence of hydropericardium in birds receiving Aroclor 1254. Fatty liver was observed in some birds receiving Aroclor 1242 and a single bird receiving this PCB exhibited liver necrosis. Moderate increases in liver weight and mild decreases in the relative weight of the spleen were attributable to PCB.

Adipose Tissue↗
PubMed1976

Laboratory model ecosystem evaluation of the chemical and biological behavior of radiolabeled micropollutants.

A standardized laboratory model ecosystem has been used to evaluate the comparative behavior of radiolabeled micropollutants including organochlorine, organophosphorus, carbamate, and hormone-mimic insecticides; herbicides; important industrial organic compounds including phthalate esters and PCB's; and specific pollutants such as TCBD and hexachlorobenzene. The compounds have been studies for ecological effects over a terrestrial-aquatic interface and through several food chains, especially with regard to the development of quantitative information on ecological magnification and biodegradability index. The pathways of chemical degradation in the various organisms have been evaluated and the ecological effects of degradation products investigated. Illustrations are given of the use of the model ecosystem technology for screening new candidate pesticides for effects on environmental quality; for evaluating the hazards of environmental pollution by industrial waste effluents; and for fundamental studies of the principles fo biodegradability of organic chemicals in a variety of organisms.

Animals↗