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Biomedical subjects

F A Smith

Publications and source records attributed to F A Smith.

At least 19 recordsLinked to original sources
PubMed1997

Cost-effectiveness of mandatory stress testing in chest pain center patients.

STUDY OBJECTIVE: To determine whether emergency patients with acute chest pain and low suspicion of acute myocardial infarction (AMI) can be managed cost-effectively and safely in a dedicated chest pain center (CPC) that incorporates mandatory stress testing. METHODS: We assembled a prospective observational case series of consecutive adult patients transferred from the emergency department to a nine-bed, 23-hour CPC in a 564-bed community hospital from January 13 through May 31, 1994. In our institution, all emergency patients with acute nontraumatic chest pain of unclear origin, suggestive of myocardial ischemia but with a low probability of AMI, are transferred to the CPC for further evaluation. All patients in whom AMI is ruled out undergo individually appropriate cardiac diagnostic testing in accordance with CPC clinical guidelines. Patients with end-stage coronary artery disease transferred to the CPC for a "rule-out" protocol only did not undergo further diagnostic testing. Admitted and discharged patients were followed through chart review and telephone survey, respectively. RESULTS: Of the 502 patients transferred to the CPC, 477 (95%) completed follow-up at 14 days. Four hundred ten (86%) were discharged home. Those discharged after diagnostic evaluation yielded negative findings had 100% survival and zero diagnosis of AMI at 5-month follow-up. Overall mortality and incidence of AMI on long-term follow-up for all patients transferred to the CPC were .4% and .2%, respectively. Sixty-seven patients (13%) were admitted from the CPC, of whom 44 (66%) had a final diagnosis of ischemic heart disease (IHD) or AMI. Twenty-four patients with IHD (55%; 6% of stress-tested group) were identified only on further stress testing. Of these patients, seven underwent percutaneous transluminal coronary angioplasty or coronary artery bypass grafting during hospitalization. All were discharged home without major morbidity. Four hundred twenty-four patients (84%) underwent stress testing. The cost of mandatory stress testing to identify one patient with IHD after AMI was ruled out was $3,125. An average cost-per-case savings of 62% was achieved for each patient transferred to the CPC who would have been hospitalized before the inception of the CPC. CONCLUSION: Mandatory stress testing is a safe, cost-effective, and valuable diagnostic and prognostic tool in CPC patients.

Acute Disease↗
PubMed1997

Optimal procedures for detecting analytic bias using patient samples.

We recently described the performance characteristics of the exponentially adjusted moving mean (EAMM), a patient-data, moving block mean procedure, which is a generalized algorithm that unifies Bull's algorithm and the classic average of normals (AON) procedure. Herein we describe the trend EAMM (TEAMM), a continuous signal analog of the EAMM procedure related to classic trend analysis. Using computer simulation, we have compared EAMM and TEAMM over a range of biases for various sample sizes (N or equivalent smoothing factor alpha) and exponential parameters (P) under conditions of equivalent false rejection (fixed on a per patient sample basis). We found optimal pairs of N and P for each level of bias by determination of minimum mean patient samples to rejection. Overall optimal algorithms were determined through calculation of undetected lost medical utility (ULMU), a novel function that quantifies the medical damage due to analytic bias. The ULMU function was calculated based on lost test specificity in a normal population. We found that optimized TEAMM was superior to optimized EAMM for all levels of analytic bias. If these observations hold true for non-Gaussian populations, TEAMM procedures are the method of choice for detecting bias using patient samples or as an event gauge to trigger use of known-value control materials.

Algorithms↗
PubMed1997

Twenty-four-hour pharmacokinetics of rectal acetaminophen in children: an old drug with new recommendations.

BACKGROUND: Rectal acetaminophen is often administered during operation to provide supplemental analgesia or antipyresis in children. Recent studies examining current dose guidelines are limited by short sampling times. The authors extended the drug sampling period to more clearly define acetaminophen pharmacokinetics in children having surgery. METHODS: Children (n = 28) were randomized to receive a single dose of 10, 20, or 30 mg/kg rectal acetaminophen after induction of anesthesia. Venous blood samples were taken every 30 min for 4 h, every 60 min for 4 h, and every 4 h for 16 h. Data were analyzed using a mixed-effects modeling technique (using NONMEM software) to determine the volume of distribution and clearance normalized for bioavailability. Additional models accounted for suppository dissolution followed by acetaminophen absorption. RESULTS: Age, weight, estimated blood loss, volume of intravenous fluid administered, and anesthesia time were similar in the three groups. Most patients did not achieve peak or sustained serum values in the 10-20 microg/ml serum concentration range associated with antipyresis. The volume of distribution was 385 ml/kg, and clearance normalized for bioavailability, F, was 5.46 ml x kg(-1) x min(-1). Pharmacokinetic models suggest that absorption of acetaminophen is a function of zero-order dissolution of suppositories and first-order absorption from the rectum. Suppository dose size also may affect absorption characteristics. CONCLUSIONS: The current recommended rectal acetaminophen dose of 10-15 mg/kg yields peak serum concentrations less than the antipyretic serum concentration of 10-20 microg/ml. Based on the observed kinetics, the authors recommend that the initial dose should be approximately 40 mg/kg.

Acetaminophen↗
PubMed1996

Exponentially adjusted moving mean procedure for quality control. An optimized patient sample control procedure.

The idea of using patient samples as the basis for control procedures elicits a continuing fascination among laboratorians, particularly in the current environment of cost restriction. Average of normals (AON) procedures, although little used, have been carefully investigated at the theoretical level. The performance characteristics of Bull's algorithm have not been thoroughly delineated, however, despite its widespread use. The authors have generalized Bull's algorithm to use variably sized batches of patient samples and a range of exponential factors. For any given batch size, there is an optimal exponential factor to maximize the overall power of error detection. The optimized exponentially adjusted moving mean (EAMM) procedure, a variant of AON and Bull's algorithm, outperforms both parent procedures. As with any AON procedure, EAMM is most useful when the ratio of population variability to analytical variability (standard deviation ratio, SDR) is low.

Algorithms↗
PubMed1996

Design and assessment of average of normals (AON) patient data algorithms to maximize run lengths for automatic process control.

Achieving high quality and high productivity with automated testing processes will require process control systems that are optimized for the necessary error detection, minimum false rejection, and maximum run length. This study investigates whether run length could be monitored by average of normals (AON) algorithms that truncate the patient test distribution and estimate the average of a suitable number of patient results. The design of AON algorithms for individual analytes is facilitated by computer-simulated power curves that consider the ratio of the population biological variation (Spop) to the test method variation (Smeas), represent a range of Spop/Smeas ratios from 2 to 15, and include numbers of patient test results from 10 to 600. The potential applications of AON algorithms are assessed for 38 tests whose quality requirements represent the total error criteria from the Ontario Medical Association Laboratory Proficiency Testing Program, Spop/Smeas ratios from 0 to 32, critical systematic shifts from 0.02 to 10.85 Smeas, and test workloads representative of a regional reference laboratory. Approximately half of these tests provide high potential for applying AON algorithms to monitor run length.

Algorithms↗
PubMed1994

Route-dependent comparative metabolism of [14C]toluene 2,4-diisocyanate and [14C]toluene 2,4-diamine in Fischer 344 rats.

This study was initiated to evaluate the pharmacokinetics/metabolism of 14C-labeled toluene 2,4-diisocyanate (2,4-[14C]-TDI) following oral and inhalation exposure in the rat. For comparison, the pharmacokinetics/metabolism of toluene 2,4-diamine (2,4-[14C]TDA) was also evaluated. Groups of 3 or 4 male rats were given either a single 60 mg/kg oral dose of 2,4-[14C]-TDI or were exposed to 2,4-[14C]TDI vapors at a target concentration of 2 ppm for a 4-hr period. Additional groups of male rats were given single 3 or 60 mg/kg oral doses or a single 3 mg/kg intravenous (iv) dose of 2,4-[14C]TDA. All rats were euthanized by 48 hr postexposure. Following oral administration of 2,4-[14C]TDI, > 93% of the administered radioactivity was recovered in the urine, feces, cage wash, and tissues. Approximately 8% of the oral dose was excreted in the urine while 81% was eliminated in the feces. It is estimated that during inhalation exposure, essentially all of the inhaled 2,4-[14C]TDI was retained by the animal. At 48 hr post-inhalation exposure approximately 15 and 47% of the recovered radioactivity was in the urine and feces, respectively. Following oral or inhalation exposure to 2,4-[14C]TDI, no radioactivity was eliminated as either expired 14C organics or 14CO2. Comparison of the 2,4-[14C]TDI inhalation group with the oral 2,4-[14C]TDI and 2,4-[14C]TDA treatment groups indicated that a larger percentage of the inhaled radioactivity was in the tissues/carcass (34% vs 2-4%) and the excretion of radioactivity into the urine was slower (t1/2 = 20 hr vs 5-8 hr) following TDI inhalation. The total amount of free+acetylated TDA metabolites detected in the urine specimens (0-12 hr) following oral and inhalation exposure to 2,4-[14C]TDI was 15 and 0.26 microgram eq 2,4-TDA, respectively. No free 2,4-TDA was detected in the urine specimen from the inhalation group. In comparison, 638 and 20 micrograms eq 2,4-TDA was detected in the urine specimen after oral administration of 60 and 3 mg/kg 2,4-[14C]TDA, respectively. Following 2,4-[14C]TDI inhalation and oral exposure approximately 90 and 65% of the quantitated urinary metabolites existed as acid-labile conjugates, respectively. In contrast, only 16-39% of the quantitated urinary metabolites existed as acid-labile conjugates following oral administration of 2,4-[14C]TDA. Inhalation exposure to 2,4-TDI primarily results in the formation of acid-labile conjugates with little or no 2,4-TDA being formed.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗
PubMed1994

Effect of parental acceptance or rejection of a proposed aversive intervention on treatment acceptability.

Effects of parental acceptance or rejection of a proposed aversive behavioral intervention on treatment acceptability ratings were investigated. Results suggest that parental acceptance or rejection of the proposed intervention significantly affected treatment acceptability ratings. The issue of a client's right to effective treatment versus the right to be free of a restrictive or aversive intervention was the dominant issue for judges. Results were discussed in terms of the usefulness of treatment acceptability ratings in treatment decision-making.

Adolescent↗
PubMed1993

Gas chromatographic/tandem mass spectrometric identification and quantitation of metabolic 4-acetyltoluene-2,4-diamine from the F344 rat.

2,4-Toluenediamine (TDA) and 2,4-toluenediisocyanate (TDI) are metabolized in the Fischer 344 rat to monoacetyl-2,4-toluenediamine (Ac-TDA) and diacetyl-2,4-toluenediamine (Ac2-TDA). A gas chromatographic/tandem mass spectrometric (GC/MS/MS) method was developed to characterize the structure of the Ac-TDA metabolite (2-acetyl versus 4-acetyl), as a D3-diacetyl-TDA derivative. This method was also shown to be useful in the measurement of urinary levels of TDA, Ac-TDA and Ac2-TDA. Urine samples (1.0 g) were adjusted to pH 6.5-7.0, fortified with the internal standard D9-Ac2-TDA (D3-ring + D3-acetyl x 2) and extracted with ethyl acetate (2 x 2 ml). The extract residues were then derivatized with D6-acetic anhydride and analyzed via electron impact GC/MS/MS. MS/MS analysis of the D3-Ac2-TDA derivative of the two Ac-TDA isomers yielded different daughter ion spectra from the common parent ion (m/z 209). Analysis of urine samples from rats administered TDA (p.o., i.v.) and TDI (p.o., inhalation) indicated that all of the metabolic Ac-TDA from these test materials was the 4-acetyl-TDA isomer. Subsequent GC/MS analysis of the heptafluorobutyric acid (HFBA) derivative of this metabolite confirmed the MS/MS results. Selected ion monitoring of the M-acetyl daughter ions from the derivatized TDA, Ac-TDA and Ac2-TDA was shown to be a useful technique for quantitation of urinary levels of these compounds, with a detection limit of 35 ng g-1 urine for TDA and 10 ng g-1 urine for Ac-TDA and Ac2-TDA.

Animals↗
PubMed1993

The uptake and metabolism of urea by Chara australis: IV. Symport with sodium--a slip model for the high and low affinity systems.

We have previously investigated the electrogenic influx of urea in Chara, and the urea- and sodium-dependent membrane current. We have shown that there is a sodium-stimulated component of urea influx and a urea-stimulated component of sodium influx, and that these are of the same size. We conclude that the electrogenic inward transport of urea, and of its analogues acetamide and acrylamide, is by sodium symport, with a stoichiometric ratio of 1:1. The kinetics of the fluxes and currents show two different KM values for sodium in different cells and two different kinds of kinetics for the effect of urea on membrane current, one of which fits the Michaelis-Menten equation, while the other shows a maximum and fits the difference of two Michaelis-Menten terms, suggesting a phenomenon like cis-inhibition. Similarities in kinetic characteristics between the inhibitory site and the electrically silent uptake site (System II) lead us to suggest that the same protein may be responsible for both the low-KM, electrogenic influx of urea (System I) and the high-KM, electrically silent influx by System II. We suggest a "slip" model for urea uptake in Chara.

Acetamides↗
PubMed1991

Disposition and metabolism of [14C]1,2-dichloropropane following oral and inhalation exposure in Fischer 344 rats.

The objective of this study was to compare the disposition and metabolism of [14C]1,2-dichloropropane [( 14C]DCP) following oral and inhalation exposure since these two routes are of interest with regards to occupational and accidental exposure. [14C]DCP was administered orally to groups of four rats of each sex as a single dose of 1 or 100 mg/kg and as a multiple 1 mg/kg nonradiolabeled dose for 7 days followed by a single 1 mg [14C]DCP/kg dose on day 8. In addition, four rats of each sex were exposed to [14C]DCP vapors for a 6-h period in a head-only inhalation chamber at target concentrations of 5, 50 and 100 ppm. [14C]DCP was readily absorbed, metabolized and excreted after oral or inhalation exposure. For all treatment groups the principal routes of elimination were via the urine (37-65%) and expired air (18-40%). The tissues, carcass, feces and cage wash contained less than 11, 9.7 and 3.8% of the dose, respectively. The major urinary metabolites, as a group, from the oral and inhalation exposures were identified as three N-acetylcysteine conjugates of DCP, N-acetyl-S-(2-hydroxypropyl)-L-cysteine, N-acetyl-S-(2-oxopropyl)-L-cysteine and N-acetyl-S-(1-carboxyethyl)-L-cysteine. The majority (61-87%) of the expired volatile organic material was found to be parent DCP in all samples analyzed. Increasing the dose/concentration of [14C]DCP resulted in an increase in the amount of exhaled [14C]-volatile organics. The peak DCP blood concentrations (inhalation exposure) were not proportional to dose, indicating a dose-dependency in the blood clearance of DCP. Nonetheless, upon termination of exposure, DCP was rapidly eliminated from the blood. In all treatment groups, following oral and inhalation exposure the majority of the radioactivity was eliminated by 24 h postdosing and no differences were noted between sexes. Therefore, it can be concluded that in the rat the pharmacokinetics and metabolism of [14C]DCP are similar regardless of route of exposure or sex.

Administration, Inhalation↗
PubMed1991

A PAC study of the binding of 111In to a monoclonal antibody via the macrocyclic molecule 1,4,7-triazacyclononanetriacetic acid.

Time integral and time differential PAC measurements have been made from samples of 111In bound to the functionalized 9N3 macrocycle, and 111In bound to the monoclonal antibody AUA1 via the macrocycle, over the temperature range 80-350 K. Values obtained for the integrated perturbation coefficient G22 (infinity) clearly illustrate the effects which the antibody has on the angular correlation of the gamma-rays emitted by the 111In decay. Measurements of the quadrupole frequency in the 111In-9N3-AUA1 samples show a transition temperature between 250 and 275 K which was not detected in the 111In-9N3. An arrhenius plot of the temperature dependence of the correlation time for the 111In-9N3 yielded a value of 0.10 +/- 0.01 eV for the activation energy associated with molecular re-orientation, whilst a Debye plot indicated an effective volume of (10 +/- 1) x 10(-27) m3 for the same sample. Extrapolation of the Debye plot suggests a high relaxation constant which may be attributed to internal vibrational modes in the macrocycle. Comparisons are made with similar work on the plasma protein transferrin.

Antibodies, Monoclonal↗
PubMed1990

Development of a physiologically based pharmacokinetic model for chloroform.

A physiologically based pharmacokinetic model describing the disposition of chloroform in mice, rats, and humans was developed. This model was designed to facilitate extrapolations from high doses, such as those used in chronic rodent studies, to low doses that humans may be exposed to in the workplace or the environment. Kinetic constants for mice and rats were derived from in vivo experiments. Enzymatic studies conducted with samples of rodent and human tissues provided a rational basis for estimating human in vivo metabolic rate constants. Incorporation of physiological descriptions of the processes of absorption, distribution, metabolism, and excretion allowed extrapolation between different routes of exposure as well. The model was validated by comparing model predictions with experimental data gathered in mice, rats, and humans after inhalation, oral, or intraperitoneal administration of chloroform. Consistent with previous reports, the metabolic activation of chloroform to toxic intermediates was shown to occur most rapidly in the mouse, less rapidly in the rat, and most slowly in humans. Estimates of the "delivered dose" of chloroform metabolites to internal organs sensitive to chloroform toxicity were calculated. This model may be used to develop refined dose estimates for human populations exposed to low levels of chloroform in the environment.

Administration, Inhalation↗
PubMed1990

Day-to-day variability of serum cholesterol, triglyceride, and high-density lipoprotein cholesterol levels. Impact on the assessment of risk according to the National Cholesterol Education Program guidelines.

The National Cholesterol Education Program has recently published guidelines for the assessment of cardiovascular risk and goals for laboratory accuracy. To test the impact of biologic and analytic variability on the ability of a single lipid measurement to assess risk accurately, lipids were measured on three occasions in 51 volunteers. Notable day-to-day variability of total cholesterol (5%), triglyceride (20%), high-density lipoprotein cholesterol (10%), and calculated low-density lipoprotein cholesterol (8%) levels was found. Analytic variability contributed significantly to total variability of high-density lipoprotein cholesterol levels and calculated low-density lipoprotein cholesterol levels. Confidence intervals constructed around National Cholesterol Education Program cutoff points suggested that classification was reliable from a single measurement if total cholesterol value was below 4.78 (less than 185 mg/dL), between 5.56 and 5.81 (215 and 225 mg/dL), or above 6.59 mmol/L (greater than 225 mg/dL). Low-density lipoprotein cholesterol value classification from a single measurement was only accurate at below 3.00 (greater than 116 mg/dL) or above 4.50 mmol/L (greater than 174 mg/dL). This study documents significant day-to-day variability of serum lipids and suggests that patients near the National Cholesterol Education Program cutoff points may require repeated measurements to assign risk accurately.

Adult↗
PubMed1989

Evidence of conformational changes in the non-equivalent binding sites of human serum transferrin.

Samples of monoferric human serum transferrin have been prepared in which the iron occupies predominantly the N-site (sample A) and the C-site (sample B). 111In was then added in concentrations small enough to ensure that there was always an excess of specific binding sites. Because of the presence of apo-transferrin in both the samples, the occupancy by 111In in the two sites was only 75-78% C-site in sample A and only 61-65% N-site in sample B. Time differential PAC spectra showed a transition in the quadrupole frequency which took place at different temperatures, approximately 275 K in sample A and between 290 and 305 K in sample B. Debye and Arrhenius plots of the temperature dependence of the correlation time associated with molecular reorientation indicated an effective molecular volume about 50% larger than that of the hydrated diferric molecule determined by "biochemical" methods, and an activation energy for re-orientation of approximately 0.065 eV.

Binding Sites↗
PubMed1988

Some optimum conditions for proton induced ultrasoft x-ray production.

The proton beam from an AN700 van de Graaff accelerator has been used to bombard solid targets of C, TiB2, SiC, SiN, Al and Au in the energy range 250-700 keV. A study of target surface contamination, the nature of the angular dependence in the x-ray emission and the dependence of the x-ray yield on proton energy has been undertaken. Our findings suggest that the optimum target angle is 30 degrees with respect to the incident proton direction and the detector angle 90 degrees to the target surface. In a vacuum of 10(-5) Torr (approximately 1.33 mPa) and at proton currents of 50-100 muA, a carbon deposit can be expected to build up with time on the target surface to reduce the characteristic x-ray intensity from the target. In the comparison between the energy dependent yields of CK and AlK x-rays, we find a slightly smaller dependence on energy than that predicted by the empirical cross section formula of Paul (1984) although the latter is not expected to be valid down to Z = 6.

Protons↗
PubMed1987

Physiologically based pharmacokinetics and the risk assessment process for methylene chloride.

Methylene chloride (dichloromethane, DCM) is metabolized by two pathways: one dependent on oxidation by mixed function oxidases (MFO) and the other dependent on glutathione S-transferases (GST). A physiologically based pharmacokinetic (PB-PK) model based on knowledge of these pathways was used to describe the metabolism of DCM in four mammalian species (mouse, rat, hamster, and humans). Kinetic constants for the model were derived from in vivo experiments or the literature. The model was constructed to distinguish contributions from the two pathways of metabolism in lung and liver tissue, and to permit extrapolation from rodents to humans. Model validation was conducted by comparing predicted blood concentration time-course data in rats, mice, and humans with experimental data from these species. The tumor incidence in two chronic studies of DCM toxicity in mice was correlated with various measures of target tissue dose calculated with the PB-PK model. Tumor incidence correlated well with tissue AUC (area under the concentration/time curve) and amount of DCM metabolized by the GST pathway. However, tumor incidence did not correlate with the amount of DCM metabolized by the MFO pathway. Because of its low chemical reactivity, DCM is unlikely to be directly involved in carcinogenesis. Consequently, metabolism of DCM by GST appears to be important in carcinogenesis. The PB-PK model was used to estimate target doses of presumed toxic chemical species in humans exposed to DCM by inhalation or by drinking water. Target tissue doses in humans exposed to low concentrations of DCM are 140- to 170-fold lower (inhalation) or 50- to 210-fold lower (drinking water) than would be expected from the linear extrapolation and body surface area factors which have been used in conventional risk assessment methods (D. V. Singh, H. L. Spitzer, and P. D. White (1985). Addendum to the Health Assessment Document for Dichloromethane (Methylene Chloride). EPA/600/8-82/004F). The PB-BK analysis thus suggests that conventional risk analyses greatly overestimate the risk in humans exposed to low concentrations of DCM. PB-PK considerations provide a scientific basis for risk assessment, improve experimental design in chronic studies, and structure collection of quantitative metabolic constants required for risk assessment.

Animals↗
PubMed1987

Acute, pharmacokinetic, and subchronic toxicological studies of 2,4-dichlorophenoxyacetic acid.

The single-dose oral LD50 values in Fischer 344 rats for technical-grade, 2,4-dichlorophenoxyacetic acid (2,4-D), esters, and salts ranged from 553 mg/kg (isobutyl ester in females) to 1090 mg/kg (dimethylamine salt in males). The LD50 values for the acid, esters, or salts, when expressed as acid equivalents, were consistent which suggests that the acute toxicity was due to 2,4-D per se. Acute dermal LD50 values in rabbits for the acid, esters, and salts were greater than 2000 mg/kg. Overall, these results indicate that the acute oral and dermal toxicity of 2,4-D are low. Pharmacokinetics were evaluated in male Fischer 344 rats given single oral doses of 10, 25, 50, 100, or 150 mg 2,4-[14C]D/kg. The amount of 2,4-D in the plasma, kidney, and urine 6 hr postdosing indicated that the urinary elimination of 2,4-D was saturated in male rats given oral doses in excess of 50 mg/kg. Subchronic dietary studies in male and female Fischer 344 rats used dose levels of 0, 15, 60, 100, or 150 mg/kg/day of purified or technical-grade 2,4-D acid for 13 weeks. Body weight gains were decreased for both sexes at the higher dose levels of purified and technical-grade 2,4-D acid. Kidney weights were increased in all treated male rats and in females given the higher three dose levels of purified 2,4-D. Treatment-related cytoplasmic alterations were present in the renal proximal tubules of most rats given 60 mg/kg/day and higher of purified or technical-grade 2,4-D; a few females given 15 mg/kg/day also had slight alterations in the cytoplasm of the proximal tubules. A dose-related degenerative change was identified in the descending proximal renal tubules of all male rats given the highest three dose levels of either test material and some given 15 mg/kg/day. Dose levels of 100 or 150 mg/kg/day of either compound for both sexes produced minimal swelling and increased staining homogeneity in the liver cells and were associated with a slight elevation of liver weight and serum glutamic pyruvic transaminase activity. Higher dose levels of technical-grade and purified 2,4-D decreased total serum tetraiodothyronine levels in female rats, however, the morphology of the thyroid gland was normal. The no-observed-effect level (NOEL) was less than 15 mg/kg/day for both purified and technical-grade 2,4-D acid.

2,4-Dichlorophenoxyacetic Acid↗