Biomedical subjects
Publications and source records attributed to L Ritter.
Authors report their case of Fournier's gangrene on the basis of their own observations and relying on data of the literature. Complete healing can be expected of immediate radical surgery and of aggressive intensive and antibiotic treatments.
No standard methods presently exist for measuring air and surface residues in indoor environments following pesticide applications. Four studies of chlorpyrifos broadcast applications for flea control were conducted to test preliminary sampling guidelines developed by Health and Welfare Canada. Air and wipe samples were collected for 24 hr following 0.5% or 0.48% chlopryifos applications. Ventilation from open doors or windows reduced air concentrations substantially. Air concentrations also varied with sampler height; i.e., greater near the floor than at one m above the floor. Wipe sampling from aluminum foil exhibited high precision (less than 10% coefficient of variation), and wipe sampling of carpets and other surfaces did not show variability in excess of the variability in initial pesticide deposits produced by the application procedures. Residues recovered from treated surfaces decreased by 60-70% over 24 hr, while residues on untreated surfaces increased 200-300% over this period. The Guidelines for Assessment of Indoor Occupant Exposure to Pesticides developed by Health and Welfare Canada have been revised in light of these findings, and provide a set of standard procedures for monitoring indoor air and surface residues. Further studies will be required to determine human exposures and health risks resulting from indoor pesticide applications.
A cohort study of the mortality experience (1971-1985) of male Saskatchewan farmers has been conducted. This study involved linkage of records of the almost 70,000 male farmers identified on the 1971 Census of Agriculture and the corresponding Census of Population to mortality records. Pesticide exposure indices for individual farm operators for the year 1970 were derived from the 1971 Census of Agriculture records. Although the cohort as a whole had no excess mortality for any specific causes of death, including non-Hodgkin's lymphoma, significant dose-response relationships were noted between risk of non-Hodgkin's lymphoma and acres sprayed in 1970 with herbicides, as well as with dollars spent on fuel and oil for farm purposes in 1970. Using Poisson regression modeling, we found that relative risks for the highest level of herbicide use (greater than or equal to 250 acres sprayed) and fuel purchased in 1970 (greater than or equal to $900) on farms less than 1,000 acres total area were 2.2 (95% confidence interval = 1.0-4.6) and 2.3 (95% confidence interval = 1.1-4.7), respectively.
Dermal absorption of the 14C-ring-labeled phenoxy herbicides 2,4-D [(2,4-dichlorophenoxy)acetic acid], 2,4-D amine (2,4-dichlorophenoxyacetic acid dimethylamine), 2,4-D isooctyl (2,4-dichlorophenoxyacetic acid isooctyl ester), and 2,4,5-T amine (2,4,5-trichlorophenoxyacetic acid trimethylamine) was examined following topical applications of the herbicides to the back of rabbits, the back and tail of rats, the forearm and forehead of rhesus monkeys, and the forehead of human volunteers. The effect of three pesticide vehicles (water, acetone, and Esteron LV96) was also investigated. The total percent dermal absorption was calculated from the mean percent urinary recoveries from the animal tests and corrected for nonurinary excretion of the radiolabel using data from intramuscular (im) injections. The human data are reported without im correction. The reliability of animal data for modelling human dermal absorption of pesticides is highlighted.
Various methods of preparing dermal application sites in Fischer 344 rats prior to exposure to 2,4-dichlorophenoxyacetic acid dimethylamine salt (2,4-D amine) and the effect of various cleansing agents following exposure were examined by measuring recoveries of 14C-labeled 2,4-D amine in skin, postapplication cleansing solution, blood, and urine. The middorsal area of the rat was the site of application for four treatments tested: (1) hair clipping only, (2) hair clipping followed by an epilatory cream, (3) hair clipping plus shaving with an electrical razor, and (4) as in treatment 3 followed by washing with soap and water. A last preparation was the rat's tail thoroughly brushed with soap and water. The results indicated that the tail retained greater than 75% of the material, thus preventing its absorption into the blood stream and subsequent removal by cleansing. With treatment 1 the dense short hair remaining after clipping impaired the absorption of 2,4-D as evidenced by considerably lower blood and urinary levels than treatments 2-4. With preparations 1-4, 45-61% of the dose was removed with the 7-h postapplication cleansing and a further 5-6% with the subsequent 23-h cleansing. In other studies using preparation 3 above, the following cleansing agents were tested: soap and water, water, isopropanol, acetone, and Rad-Con, a foam-producing cleanser. Rad-Con removed more 2,4-D from the skin than other cleansing agents after 7 h of exposure and more than soap and water after 23 h. The percentages of 2,4-D left on the skin following either 7- or 23-h cleansing with Rad-Con were 8-12%, nearly half those following the other cleansing agents. Cleansing agents other than Rad-Con presented little advantage over soap and water. With all cleansing agents, delaying cleansing from 7 to 23 h after exposure resulted in higher blood and urinary levels of 2,4-D measured 24 h after application.
The results of two methods of analysis for measuring glove permeability to pesticides are reported. The standard ASTM F739-85 testing procedure was used to determine breakthrough times and permeation rates for four protective glove materials for two commercially available pesticide formulations. The same glove materials and pesticides then were tested using an in-house developed automated in-vitro diffusion analysis (AIDA) procedure. The ASTM and AIDA procedures both demonstrated no detectable breakthrough of Sevin 50W or 2,4-D Amine 96% for nitrile butyl rubber and polyvinyl chloride gloves. Although no breakthrough of Sevin 50W or 2,4-D Amine 96 was detected for natural rubber or neoprene gloves following the ASTM procedure, permeation was observed in 2 of 3 replicate tests for both rubber and neoprene gloves when using the AIDA method. The observed discrepancy may have been caused by a longer sampling duration for the AIDA method (16 hr) than the ASTM procedure (8 hr). Advantages of the AIDA procedure are discussed.
Pesticides are registered in Canada under the authority of the Pest Control Products Act, administered by the Department of Agriculture. Pre-market registration requirements include submission of extensive toxicology data in order to allow evaluation of potential human hazards which may be associated with exposure to pesticides. Drinking water guidelines in Canada, although under provincial jurisdiction, are generally recommended by the federal government with collaboration of provincial authorities. In 1987, 42 pesticides were selected for development of guidelines for drinking water. When complete, the 42 pesticides will represent approximately 80% of all agricultural pesticides utilized in Canada, based on active ingredient weight sold. As do many other regulatory agencies, the Department of National Health and Welfare uses two different approaches to derive health-based guidelines or maximum acceptable concentrations of pesticides in drinking water. The threshold approach assumes that there is a dose below which no adverse effect will occur. This threshold level is closely related to the experimentally determined no observed adverse effect level and, when divided by an appropriate uncertainty or safety factor, forms the basis for the establishment of the maximum acceptable concentration. The second approach is the non-threshold or risk assessment approach and this assumes that these is some probability of harm at any level of exposure. This latter approach is generally utilized for chemicals believed to be capable of causing cancer and has not been used for any of the existing 29 pesticide drinking water guidelines developed in Canada.
The dermal absorption of 14C-ring-labeled DEET (N,N-diethyl-m-toluamide) applied in acetone to the skin of Sprague-Dawley rats and rhesus monkeys for 24 h was determined. Absorption in rats dosed middorsally was 36 +/- 8% with a urinary excretion half-life (t1/2) of 20 h. Both the extent and rate of absorption in monkeys were highly dependent on anatomic site, with 14 +/- 5% (t1/2 = 4 h) penetrating the forearm, 33 +/- 11% (t1/2 = 6 h) the forehead, 27 +/- 3% (t1/2 = 7 h) the dorsal forepaw, and 68 +/- 9% (t1/2 = 8 h) the ventral forepaw. Since DEET is commonly applied frequently by the same individual, the effect of multiple exposure was investigated. No significant difference (p greater than or equal to .3) was obtained either between the total percentage absorbed dermally with single (36 +/- 8%; t1/2 = 20 h) as compared with three (31 +/- 5%; t1/2 = 16 h) DEET applications at 2-h intervals to rats, or between single (14 +/- 5%; t1/2 = 4 h) as compared with three (12 +/- 1%; t1/2 = 4 h) applications at 0.5-h intervals to monkey forearm. A DEET metabolite detected in urine 4 h following topical exposure in humans was extractable following either acid (HCl) hydrolysis or urine treatment with beta-glucuronidase and was identified as ethyltoluamide (parent ion 163; base ion 119) following HPLC purification and characterization by GC/MS.
Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) was determined in rats and rhesus monkeys. Lindane is in widespread use as a 1% cream or lotion scabicide formulation and as a 1% miticide shampoo for body lice control in humans. Results obtained following our in vivo dermal absorption procedure demonstrated that 18 +/- 4.1%, 34 +/- 5.2%, and 54 +/- 26.3% of the applied dose was absorbed following topical applications at a rate of 1.5 micrograms/cm2 (6.2 micrograms/100 microliters of acetone) of the 14C-labeled pesticide to 4.2-cm2 regions of the forearm (n = 8), forehead (n = 7), and palm (n = 4) of rhesus monkeys, respectively. Dose sites were washed with soapy water 24 h posttreatment. Comparative studies in rats (n = 5) dosed middorsally demonstrated 31 +/- 9.5% absorption. Statistical analysis of the 14C excretion kinetics demonstrated slower clearance of lindane from rats than monkey forearm, forehead, or palm. Intramuscular (im) injections of 14C-lindane gave 52 +/- 7.1% recovery in monkey (n = 8) and 64 +/- 5.9% in rats (n = 5), suggesting body storage of this lipophilic chemical.
The dimethylamine salt of 14C-ring-labeled 2,4-D was administered to Fischer 344 rats orally (1 and 0.4 mg/kg body weight) and dermally (10 mg/kg body weight). Absorption, distribution, and elimination were determined from 14C-labeled 2,4-D in blood, tissues, and excreta. Quantitatively, most of the orally administered dose (94-96%) became systemically available within 6 h. Following dermal administration 10% of the dose became systemically available over 72 h. However, peak concentrations in blood and kidneys were achieved within 30 min of dosing by either route. By 1.5 h after dosing, 2,4-D concentrations in blood, muscle, liver, and kidneys had decreased in both the orally dosed and dermally dosed animals. Between 2 and 8 h, the blood, muscle, liver and kidney concentrations in dermally dosed animals maintained a plateau while urinary excretion increased, presumably due to continued absorption of 2,4-D from the skin. The concentrations in orally dosed animals continued to decrease. Following 7 h of dermal exposure, skin cleansing removed about 63% of the applied dose; about 17% of the applied dose remained at the site of dermal dosing. At 8 h, 2,4-D concentrations in blood, muscle, liver, and kidneys of dermally dosed animals began to decrease, most likely a result of the removal of the reservoir on the skin. However, 2,4-D continued to be absorbed from skin site, resulting in a slower decline of the 2,4-D concentrations in these tissues over remainder of the 72-h study period. By comparison, in animals that had been orally dosed, the absorbed dose was almost completely excreted within 24 h.
Dermal absorption of the insecticide lindane was determined following topical application of ring 14C-labeled lindane to the tail of Sprague-Dawley rats. The tail was tested as a practical alternative to the rat mid-dorsal (back) region, and the data obtained were compared to those with rat back and with those of rhesus monkeys in our previous reports. There was no significant difference between total percentage urinary 14C recovery for rats dosed on the tail with occlusive tail covers (52 +/- 6.2%; t1/2 = 2.7 d) compared to those with nonocclusive covers (55 +/- 4.4%; t1/2 = 2.9 d). Neither the total percentage urinary recovery nor the t1/2 values obtained for the rat tail and rat back models differed significantly. Carbon-14 activity was still detectable in urine samples taken after 72 d post-treatment. However, an extensive tissue analysis failed to demonstrate 14C activity persisting at 72 d, with the exception of trace levels detected in blood serum and tail tissue. Advantages of the rat tail model are highlighted.
Pesticides are registered in Canada under the authority of the Pest Control Products Act (PCP), administered by the Department of Agriculture. The Department of Agriculture calls upon various federal departments, including Health & Welfare Canada, to provide expert advice on hazards which may be associated with the use of the product. The Department of Health and Welfare requires and reviews a range of toxicological studies to assess potential health hazards which may be associated with exposure to the chemical. Studies required include acute, sub-acute, chronic, reproduction, teratology and metabolism. In addition, exposure studies are also required to provide estimates of anticipated human exposure during typical field use of the chemical. In summary, the various steps involved in the registration of pesticides will be discussed and the relationship between the predictive toxicology as determined through animal testing and exposure estimates for estimating hazard will be shown.
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The case of a patient is reported, who developed a squamous cell cancer in a long standing anal fistula track. The observations seem to prove that irritated epithelium of chronic anal fistulas may be the source of a malignant disease.