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Biomedical subjects

C A Franklin

Publications and source records attributed to C A Franklin.

32 records · Page 2Linked to original sources

Modern biotechnology: a review of current regulatory status and identification of research and regulatory needs.

Modern biotechnology encompasses many technologies. The one that has generated the most public interest is that of genetic engineering. The field has advanced dramatically since the early 1970's, when concern was so high that a moratorium was declared on research using recombinant DNA. Today there are numerous products such as human growth hormone, interferon and monoclonal antibody diagnostic kits on the market. Despite the obvious benefits of these products, there are still concerns over the environmental application of genetically engineered organisms. Many countries have assessed their existing legislation to ascertain its adequacy to regulate such intended releases. Numerous international organizations are becoming involved as well, and optimistically, regulations that are being developed in various countries may be harmonized. These activities have identified several areas where more information is required, including microbial taxonomy and classification, pathogenicity in target and non-target species, environmental behavior and risk assessment processes. Consensus at this time appears to be that our predictive capabilities are still developing and that new organisms should be evaluated on a case-by-case basis.

Biotechnology↗

Percutaneous absorption of the insecticides fenitrothion and aminocarb in rats and monkeys.

The dermal penetration of 14C-ring-labeled fenitrothion and aminocarb was determined in rats and rhesus monkeys. In monkeys, 49 +/- 4% (t1/2 = 14 h) of the fenitrothion and 74 +/- 4% (t1/2 = 25 h) of aminocarb were absorbed from the forehead, while 21 +/- 10% (t1/2 = 17 h) fenitrothion and 37 +/- 14% (t1/2 = 31 h) aminocarb were absorbed from ventral forearm. Monkey forehead was 2.3 times and 2.0 times more permeable than the forearm for fenitrothion and aminocarb, respectively. In rats, 84 +/- 12% (t1/2 = 20 h) of the fenitrothion and 88 +/- 6% (t1/2 = 17 h) aminocarb was absorbed from the middorsal region. These results were corrected for incomplete excretion by intramuscular injections of fenitrothion in money, 95 +/- 7% (t1/2 = 12 h), and rat, 69 +/- 9% (t1/2 = 12 h), and aminocarb in monkey, 95 +/- 14% (t1/2 = 8 h), and rat, 63 +/- 6% (t1/2 = 15 h). These results suggest rapid dermal absorption of these pesticides in rats and monkeys and the use of these animal models for measuring dermal penetration is discussed.

Administration, Cutaneous↗

The effect of DEET (N,N-diethyl-m-toluamide) on dermal persistence and absorption of the insecticide fenitrothion in rats and monkeys.

The in vitro persistence of 14C-ring-labeled fenitrothion in acetone (F-A) or N,N-diethyl-m-toluamide (DEET) (F-D) vehicles was determined, and in vivo studies were conducted to determine the persistence and absorption of [14C]fenitrothion in acetone or DEET applied to the skin of rats and rhesus monkeys. In vitro persistence of [14C]fenitrothion was significantly enhanced in DEET vehicle, and the percent residual 14C activity at 24 h was positively correlated with the amount (micrograms) of DEET employed (e.g., in vitro, 98.6 +/- 1.7% 14C recovery after 24 h with [14C]fenitrothion in DEET versus 1.9 +/- 0.3% without DEET). Significantly greater (p less than 0.05) fenitrothion 14C activity was detected in skin swabs taken after 24 h at the dose site with DEET vehicle from rats [acetone (F-A): 15.0 +/- 5.8%; DEET (F-D): 31.5 +/- 3.9%)] and monkeys (F-A: 3.2 +/- 1.5%; F-D: 9.7 +/- 6.0%). A lag in the urinary excretion kinetics was observed for F-D in comparison with F-A for both rats and monkeys. The total percent urinary 14C recovery was significantly higher in rats dosed with F-A (73.0 +/- 7.4%) than with F-D (52.4 +/- 8.8%) but not in monkeys (F-A: 34.7 +/- 7.1%; F-D: 36.7 +/- 2.9%). The observed species-related differences are discussed in context with the use of animal models for predicting dermal penetration of pesticides in humans.

Animals↗

Dermal exposure and urinary metabolite excretion in farmers repeatedly exposed to 2,4-D amine.

Following multiple exposures to 2,4-D amine salts under normal field conditions in which ground rigs were used, farmers who sprayed once or twice had an average dermal exposure of 655 micrograms 2,4-D acid equivalents (a.e.)/kg a.e. sprayed and an average cumulative urinary metabolite excretion of 10.9 micrograms 2,4-D a.e./kg a.e. sprayed. One very high outlier value was excluded from these averages (F). Following 4 to 7 exposures, the average cumulative dermal exposure was 1,077 micrograms 2,4-D a.e./kg a.e. sprayed and the average cumulative urinary metabolite excretion was 21.5 micrograms 2,4-D a.e./kg a.e. sprayed. The amount of 2,4-D metabolite in urine was significantly correlated with the amount of herbicide sprayed and the time required for the urinary metabolite excretion to return to background concentration was related to the amount sprayed and the number of exposures.

2,4-Dichlorophenoxyacetic Acid↗

The use of biological monitoring in the estimation of exposure during the application of pesticides.

In order to assess the occupational health risk to workers using pesticides, accurate data on exposure (including knowledge of the primary route of exposure) and on absorption are needed. In addition, a well-defined no-effect level (NOEL) derived from suitable animal data must be available. Biological monitoring, urinary metabolite excretion in particular, frequently is used to indicate whether a worker has been exposed. Interpretation of the toxicological significance of the observed urinary metabolite levels is often difficult because the relationship between these levels and toxic dose are generally unknown. Another complication is the apparent lack of correlation between patch data and urinary metabolite data. The usefulness of a metabolite to predict exposure depends on many things, including detailed knowledge of absorption and excretion characteristics of the parent compound and identification of the metabolites. These data, when combined with appropriate toxicology data, permit an analysis of the potential health risks associated with an occupational exposure to toxic chemicals. This paper will correlate data from a number of studies in which the dermal penetration of azinphosmethyl (AM) was measured in rats, rabbits, monkeys and man; and urinary alkyl phosphate metabolites were measured in orchardists exposed to AM. The feasibility of utilizing metabolite excretion to estimate exposure and ultimate risk will be discussed.

Agriculture↗

Health risks from acid rain: a Canadian perspective.

Acidic deposition, commonly referred to as acid rain, is causing serious environmental damage in eastern Canada. The revenues from forest products, tourism and sport fishing are estimated to account for about 8% of the gross national product. The impact on human health is not as clearcut and a multi-department program on the Long-Range Transport of Airborne Pollutants (LRTAP) was approved by the federal government in June 1980. The objectives of the LRTAP program are to reduce wet sulfate deposition to less than 20 kg/ha per year in order to protect moderately sensitive areas. This will require a 50% reduction in Canadian SO2 emissions east of the Saskatchewan/Manitoba border and concomitant reductions in the eastern U.S.A. The objectives of the health sector of the program are to assess the risk to health posed by airborne pollutants which are subjected to long-range transport and to monitor the influence of abatement programs. Two major epidemiology studies were undertaken in 1983, one in which the health effects related to acute exposure to transported air pollutants were studied in asthmatic and nonasthmatic children, and another in which the effects of chronic exposure to these pollutants were studied in school children living in towns with high and low levels of pollutants. Preliminary analysis of the data do not indicate major health effects, but definitive conclusions must await final analysis. Studies on the indirect effects of acid deposition on water quality have shown that acidified lake water left standing in the plumbing system can adversely affect water quality and that federally set guidelines for copper and lead are exceeded. Flushing of the system before using the water rectifies the situation. Additional studies are planned to further delineate the magnitude of the health effects of acidified lake water.

Acids↗

Estimation of dermal exposure to pesticides and its use in risk assessment.

The potential risks to humans resulting from the usage of a pesticide must be carefully assessed before the product is registered. One of the components in the risk assessment is the determination of the amount of pesticide to which the applicator is exposed. Traditional methods estimated dermal exposure by measuring the amount of pesticide deposited on absorbent patches worn on the applicator's body. A more recent approach consists of measuring urinary metabolite levels. A review of data obtained in humans and in rats suggests that the urinary concentration of dimethyl thiophosphate is a good indicator of dermal exposure to azinphos-methyl.

Air Pollutants, Occupational↗

Correlation of urinary pesticide metabolite excretion with estimated dermal contact in the course of occupational exposure to Guthion.

Exposure to and absorption of Guthion 50 W.P. (azinphos-methyl) were estimated in orchardists from the Okanagan Valley in British Columbia who were involved in mixing, loading, and application with ultra-low volume air blast equipment. Air monitoring and patch techniques were used to estimate exposure, and alkyl phosphate excretion and cholinesterase inhibition were measured to estimate absorption. All workers were issued with standardized cotton shirts, trousers, and long-sleeved coveralls. All wore half-face respirators, gloves, boots, and hats. Eight wore rubberized protective clothing in addition. The indirect method of measuring urinary metabolites appeared to be the most sensitive. All workers had quantifiable levels of alkyl phosphates following exposure, and 24-h urine samples provided a more reliable estimate than first morning voids. A high correlation was observed between 48-h alkyl phosphate excretion and amount of active ingredient sprayed. A fluorescent tracer was added to the tank along with the Guthion. The finding of Guthion on patches beneath the clothing was confirmed by the presence of the tracer on the skin. With the ultralow-volume application used in this study, the rubberized clothing did not appear to be significantly more protective than the heavy coverall. There was no significant depression of either red blood cell or serum cholinesterase activity in any workers.

Air Pollutants, Occupational↗

The accumulation of mono-2-ethylhexylphthalate (MEHP) during storage of whole blood and plasma.

The accumulation of the plasticizer di-2-ethylhexylphthalate (DEHP) in blood and blood components has been of considerable concern for some time. We have followed the accumulation of DEHP and one of its major metabolities, mono-2-ethylhexylphthalate (MEHP) during storage of whole blood, platelet-rich plasma, platelet concentrates, and platelet-poor plasma for periods ranging from 72 hours to four weeks. Both phthalates showed a progressive increase in concentration with time. While the levels of DEHP were much greater than those of MEHP, there was nonetheless a significant and continual increase in MEHP in all preparations. The highest concentrations of both DEHP and MEHP were found in the platelet-poor plasma, indicating that platelets do not have a major role in the accumulation of the phthalates in blood. The accumulation of MEHP was shown to be a direct result of the metabolism of DEHP by plasma protein(s) rather than leaching from the blood bag.

Blood Platelets↗