The recognition of diazinon, an organophosphorus pesticide, when found in samples in the form of decomposition products.

The contents of a bottle, from which a human being was reported to have drunk and which were believed responsible to an organophosphorus poisoning, were submitted for chemical analysis. Initial screening by gas chromatography with phosphorus, sulfur, and nitrogen specific detectors failed to identify any intact organophosphorus pesticide. Mass spectrometric techniques were applied to the identification. Field ionization, field desorption, chemical ionization, exact mass measurements at high resolution, and GC/low resolution mass spectrometry were used to help define the qualitative and partial quantitative nature of the sample components. Results of this study were consistent with the virtually complete conversion of the pesticide, diazinon [Chemical Abstracts reference number 333-41-5], into a mixture of at least twenty-six chemically distinct products or impurities. The most abundant chemical compounds found in the sample included: 2-isopropyl-4-methyl-6-hydroxypyrimidine [2814-20-2]; 2-isopropyl-4-methyl-6-mercaptopyrimidine; 6,6'-dithiobis-(2-isopropyl-4-methylpyrimidine); 6,6'-dithiobis-(2-isopropyl-4-methylpyrimidine); 4-ethoxy-2-isopropyl-6-methylpyrimidine [72799-31-6]; 4-thioethoxy-2-isopropyl-6-methylpyrimidine; triethylphosphorothiolate and triethylphosphorothiolate. Also found were several potent acetylcholinesterase inhibitors: monothionotetraethylpyrophosphate; dithionotetraethylpyrophosphate [3689-24-5]; tetraethylpyrophosphate. Model decomposition studies verified the formation of these compounds. These results were then used to identify compounds in two other samples.

Electron capture gas chromatographic analysis of the amine metabolites of pesticides: derivatization of anilines.

A number of amines have been shown to result from metabolism of various pesticides. From an epidemiological standpoint, it may be possible to monitor human exposure to these pesticides through the excretion of their corresponding amines in urine. An investigation has been initiated to develop and apply methods of analysis of amines in human urine. The results of a survey of derivatization techniques involving several substituted anilines are presented. These include conditions for derivatization, utilizing a number of halo- and nitro- substituted reagents; electron capture and gas chromatographic properties of the derivatives; and stability of the derivatives to extraction and column chromatography for purposes of separation and cleanup. The recoveries of anilines from spiked water and urine samples at the 1.0 ppm and 0.1 ppm levels were between 85 and 90%. The advantages and disadvantages of the various derivatives and techniques are discussed and a rationale is presented for the preliminary selection of a particular derivative for application of the analysis of aniline metabolites in urine.

Organophosphorus pesticide poisonings in humans: determination of residues and metabolites in tissues and urine.

The analyses of four organophosphorus pesticide poisoning cases, three of which resulted in death, are reported. The case histories of the subjects, along with the analysis of tissues, urine, and blood for the levels of pesticides and metabolites are given. The pesticides involved include dicrotophos, chlorpyrifos, malathion, and parathion. The methods of analysis were adapted from previously published methods that provide a very rapid means of identification of organophosphorus pesticides in the tissues or in the blood of poisoned patients.

Perspectives on interactions with QA--the regulatory perspective.

It has been my experience that the quality assurance unit (QAU) normally serves as the facility point-of-contact with the agency on matters relating to a Good Laboratory Practice (GLP) compliance inspection. The QAU usually receives the notification letter, does most of the coordinating for the GLP inspection, and often bears the criticism for deficiencies found during the inspection. In general, as inspectors, we have found it difficult to get management to show any interest in the inspection and, in many facilities, have been forced to communicate almost entirely with the QAU. The evolution of the relationship between regulators and the QA community, which parallels the evolution of the image of quality assurance personnel from inexperienced technicians to recognized professionals, is discussed. Also discussed are both typical and atypical examples of interaction between government inspectors and quality assurance units.

Laboratory accreditation.

An investigation of alleged data fraud at a pesticide analytical laboratory led EPA to take a closer look at the Good Laboratory Practice (GLP) inspection program. There was special focus on changes which might be made in the program to enhance the chances of detecting fraud in regulated studies. To this end, the Assistant Administrator of the Office of Prevention, Pesticides and Toxic Substances (OPPTS) requested EPA's Office of Inspector General (OIG) to examine the GLP program. Several reports were issued by the OIG, including the recommendation that a laboratory accreditation program be adopted. EPA has been examining ways to implement the OIG's recommendations, including (1) laboratory accreditation consisting of three components: document submission and assessment, site visit and assessment, and proficiency assessment; and (2) mandatory registration of all facilities participating in GLP-regulated studies, based on document submission and assessment. These two alternatives are compared, and the advantages and disadvantages of each are discussed.

Worker exposure to ethion in Florida citrus.

Dermal and respiratory exposure to ethion was determined for 17 men in eight spray crews in Florida citrus spray operations. Respiratory exposure was less than 1% of the total exposure. Hands represented 42% of the total body exposure for applicators and 76% for suppliers. At one location, suppliers exhibited a larger decrease in ChE activity than applicators. This difference appeared related to the higher mean dermal ethion exposure to suppliers. Acute symptoms of organophosphorous poisoning were not observed. The total percent/hr of the probable human dermal LD50 was very low in all cases. These data indicate a relatively low potential acute hazard to workers applying ethion with air blast equipment under the conditions of this study.

Human subject experiments to estimate reentry periods for monocrotophos-treated tobacco.

Thirteen to fifteen human volunteers worked for eight-hr periods in tobacco fields treated 96, 72, and 48 hr previously with monocrotophos (3-hydroxy-N-methyl-cis-crotonamide dimethyl phosphate). At the 48-hr reentry period, during which time no rainfall occurred, both post-exposure plasma and red blood cell cholinesterase levels of the worker group were depressed from pre-exposure levels although the decline was less than 9% in both cases. Rainfall in excess of one inch fell during the 96- and 72-hr reentry intervals, and no important change in cholinesterase levels was noted. Experiments with mice were in general agreement with the human tests. Dimethyl phosphoric acid in urine of the worker group collected prior to, and three hr after, exposure was unchanged in all cases. Rain appeared to have markedly reduced dislodgable residues.