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Biomedical subjects

L G Hansen

Publications and source records attributed to L G Hansen.

At least 91 records · Page 5Linked 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↗
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↗
PubMed1983

Biotransformation of organophosphorus compounds relative to delayed neurotoxicity.

In summary, although there is considerable information on he biotransformation of OP compounds, there are some deficiencies in our knowledge of the biotransformation of phosphonothionate delayed neurotoxicants. Various anomalies, such as the species variations, limited absorption and unique disposition, phenyl phosphonothionate vs. alkyl phosphonothionate potency, O-methyl phenylphosphonothionate vs. O-ethyl phenylphosphonothionate potency, and the relative contributions of various activation and detoxication pathways still exist. The understanding of the syndrome of delayed neurotoxicity will come from receptor/mechanism studies, but by increasing our knowledge of comparative biotransformation, we can insure that our concepts are less distorted by "extraneous" influences. Moreover, since the ultimate goal is to define the syndrome as it relates to the whole organism for predictive and safety considerations, influences such as biotransformation and disposition are no longer extraneous but critical.

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↗
PubMed1981

Biological activity of technical Aroclor 1254 compared to Aroclor 1254 residues: swine fat residues fed to broiler cockerels.

Fat from Aroclor 1254-treated swine was rendered and incorporated into the diets of broiler chicks for 3-4 weeks. The technical Aroclor 1254 which was fed to the swine was also mixed into control lard for comparison at dietary concentrations of 0.07-9.0 mg/kg. The swine-residue PCB seemed to have a higher proportion of strong microsomal inducers, but the technical PCB was slightly more effective in inducing ethoxy resorufin and p-nitro-anisole (pNA) O-dealkylases than the swine-residue PCB. No overt signs of toxicosis were apparent and none of the diets resulted in changes in growth, relative organ weights, microsomal protein or high affinity pNA O-dealkylase. Increases in cytochrome(s) P-450 were significant only at the higher dietary concentrations (approx. 9 mg/kg) while ethoxyresorufin O-dealkylase was induced at dietary concentrations below 1 mg/kg.

Adipose Tissue↗
PubMed1981

Sub-acute toxicity of hexachlorobenzene in female beagles, including electroencephalographic changes.

Adult female beagles were given oral HCB for 21 days. Subdividing the dose resulted in greater accumulation of HCB in fat and seemed to enhance toxic effects. Subjecting the animals to a 10-day period of food restriction immediately following 21 days of dosing further increased residues, but obscured any differences due to dosing regimen. Liver and hepatocyte enlargement, as well as physiologic changes in the central nervous system, were HCB-induced. Weight loss and various hematological changes were equivocal, with dietary stress and HCB probably contributing to the changes to varying degrees. A dose of 50 mg/kg/day of HCB for 21 days must be considered at least minimally toxic to female beagles.

Animals↗
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↗