Postapplication Fipronil Exposure Following Use on Pets.

Fipronil is a pyrazole acaricide and insecticide that may be used for insect, tick, lice, and mite control on pets. Residents' short-term and long-term postapplication exposures to fipronil, including secondary environmental exposures, were estimated using data from chemical-specific studies. Estimations of acute (24-h) absorbed doses for residents were based on U.S. Environmental Protection Agency (U.S. EPA) 2012 standard operating procedures (SOPs) for postapplication exposure. Chronic exposures were not estimated for residential use, as continuous, long-term application activities were unlikely to occur. Estimated acute postapplication absorbed doses were as high as 0.56 µg/kg-d for toddlers (1-2 yr) in households with treated pets based on current U.S. EPA SOPs. Acute toddler exposures estimated here were fivefold larger in comparison to adults. Secondary exposure from the household environment in which a treated pet lives that is not from contacting the pet, but from contacting the house interior to which pet residues were transferred, was estimated based on monitoring socks worn by pet owners. These secondary exposures were more than an order of magnitude lower than those estimated from contacting the pet and thus may be considered negligible.

Implications of estimates of residential organophosphate exposure from dialkylphosphates (DAPs) and their relevance to risk.

Recent epidemiological studies have claimed to associate a variety of toxicological effects of organophosphorus insecticides (OPs) and residential OP exposure based on the dialkyl phosphates (DAPs; metabolic and environmental breakdown products of OPs) levels in the urine of pregnant females. A key premise in those epidemiology studies was that the level of urinary DAPs was directly related to the level of parent OP exposure. Specific chemical biomarkers and DAPs representing absorbed dose of OPs are invaluable to reconstruct human exposures in prospective occupational studies and even in non-occupational studies when exposure to a specific OP can be described. However, measurement of those detoxification products in urine without specific knowledge of insecticide exposure is insufficient to establish OP insecticide exposure. DAPs have high oral bioavailability and are ubiquitously present in produce at concentrations several-fold greater than parent OPs. Studies relying on DAPs as an indicator of OP exposure that lack credible information on proximate OP exposure are simply measuring DAP exposure and misattributing OP exposure.

Characterization of ruminal dynamics in Holstein dairy cows during the periparturient period.

We used four pregnant Holstein cows to delineate ruminal adaptations as cows transitioned from one lactation to the next. Cows were fed typical diets through far-off and close-up dry periods and lactation. We measured ruminal characteristics on day 72 (late lactation), 51 (far-off dry), 23 and 9 (close-up dry) prepartum and on days 6, 20, 34, 48, 62, 76 and 90 postpartum (early lactation). Measurements included: ruminal fill (weight of actual contents), ruminal capacity (volume of rumen when fully filled), digestibilities and ruminal passage rates. Ruminal capacity tended to increase linearly during early lactation but was stable during dry and transition periods. Both total and liquid fill decreased linearly during the dry period, increased across parturition, and increased linearly through early lactation. Dry matter fill decreased as cows were fed the close-up diet at day 23 prepartum then increased near parturition and continued to increase across early lactation. Solid passage rate was greatest when cows were fed the close-up diet, and decreased throughout the transition period. In lactation, solid passage rate responded quadratically with peak at day 48 followed by decreases through day 90 postpartum. Liquid passage increased linearly across the transition period. Total tract organic matter digestibilities increased linearly over the dry period with significant increases prior to or immediately after parturition, then they remained relatively stable over early lactation until they increased at day 90. Fibre digestibilities demonstrated quadratic responses over early lactation, being higher on day 6 and day 90 than at other times. Starch digestibilities decreased linearly across both the dry and transition periods with decreases in lactation until day 62 followed by increases until day 90. High producing lactating dairy cows go through a multitude of ruminal adaptations, in terms of digestion, passage, capacity and fill, as they transition from one lactation to the next.

Echinoid spawning induced by a radial nerve factor.

An extract of radial nerves of the sea urchin. Strongylocentrotus purpuratus, induces spawning within 1 minute in this species as well as in other echinoids, but a delayed spawning in several asteroid species. The concentration of the spawn-inducing factor in the radial nerves fluctuates annually correlated with the reproductive season of this species along the coast of southern California.

Spontaneous benign prostatic hyperplasia in the beagle. Age-associated changes in serum hormone levels, and the morphology and secretory function of the canine prostate.

This paper is a cross-sectional study of spontaneous benign prostatic hyperplasia (BPH) in a single canine species. The effects of aging and hormonal changes on the growth, histology, and glandular secretory function of the canine prostate were studied in 42 male beagles ranging in age from 8 mo to 9 yr. The beagle prostate enlarges for at least 6 yr, whether normal or hyperplastic. In contrast, prostatic secretory function, determined by ejaculate volume and total ejaculate protein, declines markedly after 4 yr of age. These reciprocal growth and functional changes in the prostate are closely associated with a progressive increase in the incidence of BPH, which is already apparent in some dogs by age two. With age there is a modest decrease in serum androgen levels with no apparent change in serum 17 beta-estradiol levels. This suggests that the growth and functional changes that are associated with the development of BPH and are initiated very early in life reflect an altered sensitivity of the prostate to serum androgens or a response to the relative decrease in the serum androgen to estrogen ratio.

Testosterone secretion by rat, rabbit, guinea pig, dog, and hamster testes perfused in vitro: correlation with Leydig cell ultrastructure.

Stereological methods were employed to determine volume and surface densities of cytoplasmic organelles in Leydig cells of hamster, rat, rabbit, dog, and guinea pig testes. Contralateral testes were perfused in vitro with maximally stimulating gonadotropin concentrations to determine the capacity of these testes to secrete testosterone. Significantly different amounts of testosterone were secreted by in vitro perfused testes of the five species when maximally stimulated with ovine LH. Significant differences also were seen in the volume and surface densities of smooth endoplasmic reticulum, mitochondria, rough endoplasmic reticulum, and lipids in Leydig cell cytoplasm of the five species. Most interestingly, linear positive correlations were seen between testosterone secretion and smooth endoplasmic reticulum volume (r = 0.99) and surface (r = 0.99) densities. Thus, virtually all of the differences in testosterone secretion by maximally stimulated testes of five species could be accounted for by between-species differences in the amount of Leydig cell smooth endoplasmic reticulum.

Testosterone secretion by rat, rabbit, guinea pig, dog, and hamster testes perfused in vitro: correlation with Leydig cell mass.

Testes from guinea pigs, rabbits, dogs, rats, and hamsters perfused in vitro with maximally stimulating concentrations of ovine LH released 9.76 +/- 2.05, 12.80 +/- 3.15, 28.94 +/- 3.01, 3.18 +/- 0.41, and 0.70 +/- 0.12 microgram testosterone (T)/h, respectively. Adjusting for differences in testicular weight did not eliminate significant (P less than 0.01) species variation in testicular capacity for T secretion in response to ovine LH. Similarly, correction for Leydig cell mass, as determined by morphometric analysis, still left significant (P less than 0.01) differences in the testosterone secretion rates in response to ovine LH for guinea pigs (262.5 +/- 38.6 micrograms T/g Leydig cell), rabbits (205.5 +/- 50.7 micrograms T/g Leydig cell), dogs (116.4 +/- 14.8 micrograms T/g Leydig cell), rats (83.55 +/- 21.80 micrograms T/g Leydig cell), and hamsters (18.24 +/- 3.55 micrograms T/g Leydig cell). The data suggest that significant between-species variation of T production in response to ovine LH is not due to quantitative differences in the mass of Leydig cells.

Effect of luteinizing hormone on Leydig cell structure and testosterone secretion.

Hypophysectomy or sc implantation of testosterone-estradiol 17 beta (T-E) filled polydimethylsiloxane capsules for 5 days caused a dramatic reduction in testosterone secretion when testes subsequently were perfused in vitro. The diminution in testosterone-secreting capacity of testes from T-E treated rats was coupled closely with reductions in the membrane surface areas of Leydig cell cytoplasmic organelles, particularly those of the smooth endoplasmic reticulum. Simultaneous treatment of T-E implanted rats with LH (12 micrograms/day), but not with FSH, PRL, TSH, or GH, maintained both the Leydig-cell cytoplasmic membranes and the capacity of testes to secrete testosterone in vitro. Testosterone secretion by testes from hypophysectomized rats treated simultaneously with T-E plus LH was identical to that in control rats. Therefore, T-E did not inhibit directly the Leydig cell steroidogenic apparatus. Taken together these results suggest that one of the trophic effects of LH in the Leydig cell is to maintained the integrity of smooth endoplasmic reticulum and enzymes responsible for the conversion of pregnenolone to testosterone.

Testicular androgen and estrogen secretion and benign prostatic hyperplasia in the beagle.

The natural history of benign prostatic hyperplasia (BPH) in the dog is characterized by a slow progression through two phases. The early phase of the disease process is characterized by glandular hyperplasia and occurs as early as 2.5 yr of age. The late phase of the disease is characterized by cystic hyperplasia and occurs after 4 yr. The results of the present study are the first to compare Leydig cell structure and steroidogenic function in dogs with BPH with those in age-matched controls. It was discovered that glandular BPH can occur in young dogs (2.5 yr) in which Leydig cell mass and ultrastructure and maximally stimulated androgen secretion are indistinguishable from those in age-matched controls. These results support the concept that the early phase of BPH (glandular hyperplasia) is not related temporally to some defect in the Leydig cell. In contrast, the late phase of BPH (cystic hyperplasia) in beagles 6 yr of age is associated with diminished smooth endoplasmic reticulum in the Leydig cell and with diminished production of androgens by perfused testes in vitro. During the course of these studies, we discovered that the testes of young beagles with BPH, but not age-matched controls or old beagles with BPH, secrete an unidentified molecule (putative estrogen). This molecule was characterized partially in that it is extractable from testicular venous effluent with diethyl ether, elutes in a discrete fraction in several different high performance liquid chromatographic systems, reacts with an antibody that recognizes 17 beta-estradiol, estrone, and estriol, and competes with 17 beta-[3H]estradiol for the rat uterine estrogen receptor. Based on the elution volume from high performance liquid chromatography, the unknown molecule (putative estrogen) is not estriol, estradiol, or estrone.

Subtotal colectomy for obstructing carcinoma of the left colon.

This retrospective review of seven patients with completely obstructing cancers of the left half of the colon, in addition to other reports in the literature, suggests that subtotal colectomy with primary ileal proctostomy may be the treatment of choice for those lesions that are technically resectable and located high enough to permit an intraperitoneal ileal proctostomy. The morbidity and mortality is less than that seen with the staged approach and the length of hospitalization is shorter. By eliminating a second or third hospitalization and a temporary colostomy, palliation is better in those patients who ultimately die from recurrent cancer. Furthermore, those patients resected for cure may have increased rates of long-term survival.

Cholecystectomy with and without drainage. A randomized, prospective study of 300 patients.

A randomized, prospective study of 300 cholecystectomies was undertaken to evaluate the merits of drainage through a standard Penrose or Chaffin-Pratt sump tube matched against no drainage at all. There was no difference in mortality or length of hospital stay. There was, however, a significantly higher incidence of postoperative pyrexia due to atelectasis and wound infection in the drainage groups. Neither drain fulfilled its objective of providing outflow for a subhepatic collection, thus avoiding bile peritonitis. This study suggests that surgical drainage after every uncomplicated cholecystectomy is unnecessary and unwise.

Surgical morbidity after mastectomy operations.

The records of 146 consecutive patients with mastectomy operations over a three year period were reviewed. Of these, ninety-three (63.6 per cent) had one or more complications secondary to surgery. There were 175 complications, of which complications, of which 107 (73.2 per cent) were wound-related. Seroma formation occurred most frequently but was of minor consequence. The incidence of flap necrosis was 19.1 per cent, with cellulitis or suppurative infection appearing in thirteen patients. Immediate postoperative edema of the arm was fairly rare (2.7 per cent) and appeared related to delayed wound healing. Postoperative complications after total, modified radical, and radical mastectomy present problems unique from those seen after other major surgery, in that local complications predominate. The very nature of the procedure, with the creation of large thin skin flaps, extensive axillary dissection, and an open wound for a prolonged period of time, predisposes to wound morbidity.

Risks from occupational and dietary exposure to mevinphos.

Mevinphos (trade name, Phosdrin), a category 1 organophosphorus insecticide, has been used mainly as a cleanup pesticide for vegetable crops. A risk assessment for occupational and dietary exposure to mevinphos was initiated because of the high acute toxicity of the compound. Repetitive dosing with mevinphos did not cause any discernible histopathological effects in mice or rats, nor was it oncogenic in either species. The principal toxic effects of mevinphos, both short- and long term, were due to inhibition of cholinesterase activity. Consequently, potential adverse effects from short-term exposures were the primary concern. A human no-observed-effect level (0.025 mg/kg) for cholinergic signs was used as the regulatory basis for calculating margins of safety (MOSs) for potential acute dietary and short-term occupational exposures. Estimates of exposure to mixer/loaders, pilots, and flaggers associated with aerial application of mevinphos were based on passive dosimetry. Because no acceptable exposure studies for work tasks associated with ground application of mevinphos were available, surrogate data based on ground application of oxydemeton-methyl were used. Exposure estimates for field workers and harvesters relied on measured dislodgeable foliar residues of mevinphos and transfer factors generated from studies of other active ingredients. MOSs for mean acute occupational exposure of mixer/loader/applicators associated with ground application and of harvesters working in fruit trees were less than the value conventionally recommended to protect people from the toxic effects of mevinphos. MOSs for the 95th percentile of short-term worker exposure for all mixer/loader work categories associated with mevinphos application were also inadequate. Calculated MOSs for potential acute dietary exposure to measured residue levels of mevinphos were adequate for the various population subgroups. However, 25 of the USEPA tolerances for mevinphos on agricultural commodities were not adequate to protect for the toxic effects of mevinphos from theoretical acute dietary exposure to one or more population subgroups if commodities are consumed with residues at the tolerance level. When the mean short-term occupational exposures were combined with potential acute dietary exposure, the MOSs for mixer/loaders engaged in aerial applications, as well as ground applications, were inadequate to protect people from the toxic effects of mevinphos. As mitigation of the estimated excessive occupational exposures did not appear possible, both California and the USEPA were preparing to cancel registration of the product. However, an agreement was worked out between the manufacturer and the two agencies that ended production for domestic use but allowed existing stocks in the channels of trade to continue to be used for a limited period.

Testis function in rhesus monkeys treated with a contraceptive steroid formulation.

Rhesus monkeys (Macaca mulatta) were treated with testosterone (100 micrograms/kg/day) plus estradiol (0.5 micrograms/kg/day) via subcutaneous polydimethylsiloxane (PDS;Silastic) implants for thirteen months. This steroid regimen inhibited LH but not FSH secretion by the anterior pituitary, inhibited testicular testosterone and estradiol production and drastically reduced the numbers of vigorously motile spermatozoa in the ejacula. Importantly, these effects on testis function were achieved at dosages of testosterone and estradiol which approximate the amount of these two steroids produced daily in normal rhesus males.

Somatic tissue responses of male rhesus monkeys treated with a contraceptive steroid formulation.

Rhesus monkeys (Macaca mulatta) were treated with testosterone (100 micrograms/kg/day) plus estradiol (0.5 micrograms/kg/day) via subcutaneous polydimethylsiloxane (PDS; Silastic) implants for thirteen months. This steroid regimen inhibited dramatically spermatogenesis. Gross and histopathological examination of the musculoskeletal, circulatory, endocrine (excluding the testis), central nervous, gastrointestinal and respiratory systems failed to uncover any untoward effects of the long-term exposure due to the contraceptive formulation. Similarly, no remarkable effects were observed in the ionic, chemical and formed elements of blood or secondary sex structures. Failure to detect secondary complications attributed to the steroid treatment offers further justification for evaluating a contraceptive strategy based on administering naturally occurring steroids at sustained rates approximating those at which they are produced endogenously in the human male.

Chlorpyrifos: hazard assessment based on a review of the effects of short-term and long-term exposure in animals and humans.

Analyses of potential dietary exposure to chlorpyrifos residues were conducted by the Department of Pesticide Regulation (DPR). Potential acute dietary ingestion of chlorpyrifos for all labelled uses was based on the 95th percentile of user-day exposures. Margins of safety (MOSs) for potential acute dietary exposure to chlorpyrifos residues were based on a no-observed-effect level (NOEL) for cholinergic signs in a human study, and ranged from 52 to 205 for all population subgroups. MOSs for potential chronic dietary exposure to chlorpyrifos residues were based on a NOEL for inhibition of brain cholinesterase activity in rats and dogs, and ranged from 2198 to 8065 for all population subgroups. The limitations on toxicity, consumption and residue data are discussed, with the assumptions necessitated by those limitations.

Prefreezing and post-thaw semen characteristics of five ram breeds collected by electroejaculation.

Rams representing five breeds were electroejaculated twice weekly, during a three-week collection period. Ejaculates were evaluated for volume and concentration before freezing and for rate of motility and percentages of motile and abnormal cells both before and after freezing. Interactions between breed and collection period were evident (P<0.05) for semen volume and post-thaw values for rate of motility and percentage motile cells. Breeds differed (P<0.05) in these traits during some periods. In contrast, pre-freezing observations of rate of motility, percentage motile and abnormal cells and post-thaw percentage abnormal cells did not differ (P>0.15) among breeds. Sperm concentration per ejaculate tended to vary (P=0.11) among breeds. Semen characteristics frequently varied across collection periods. Rams within a breed differed (P<0.01) in all semen traits except post-thaw rate of motility and percentage motile cells. Semen was negatively affected by the freezing and thawing procedure. Ram within a breed and ejaculate within ram should be considered when selecting electroejaculated semen for freezing and subsequent use in artificial insemination.

Effect of treatment with ivermectin on reproductive performance of yearling beef heifers.

To determine the effect of treatment with ivermectin on reproductive parameters, 78 fall-born, yearling heifers were allotted to either an ivermectin treatment group or to the control, non-treatment group. The heifers were treated in June and October when they were approximately 7 and 11 mo old, respectively. Ivermectin effectively lowered fecal egg counts in the treated heifers compared with that of the controls. In heifers that were maintained on a marginal plane of nutrition, treatment with ivermectin not only improved weight gains during each recording period but also hastened the onset of puberty and improved the pregnancy rate during a 60-d breeding season. The positive effect of ivermectin on these reproductive characteristics could not be explained by increased weight gain alone, because the correlation between weight gain and puberty was not significant. Treatment with ivermectin positively affected pelvic area but not uterine score when compared with those of the controls.

Performance and forage utilization by beef cattle receiving increasing amounts of alfalfa hay as a supplement to low-quality, tallgrass-prairie forage.

Two experiments evaluated effects of amount of supplemental alfalfa hay on intake and utilization of dormant, tallgrass-prairie forage by beef steers and on performance of cows grazing tallgrass prairie during winter. In Exp. 1, four supplemental alfalfa levels (.23, .47, .70, and .94% BW.steer-1.d-1) were evaluated in a 34-d, randomized complete block design experiment using 16 steers (291 kg). Voluntary tallgrass-prairie hay intake decreased linearly (P = .02), whereas total DMI increased linearly (P < .01) with increased alfalfa. Dry matter digestibility was unaffected (P > .10) by treatment, although NDF digestibility decreased (linear, P = .03) and passage rates of indigestible ADF and Cr EDTA increased (linear, P = .02) with increased alfalfa. In Exp. 2, supplemental alfalfa (.48, .72, or .96% BW.cow-1.d-1) was fed to 113 pregnant Hereford x Angus cows (502 kg) from November 27 until calving (average calving date = March 7). Cumulative weight loss from the beginning of the experiment until just after calving was lowest with .96% BW alfalfa (quadratic, P = .09), and cumulative condition loss was decreased linearly (P = .02) with increased alfalfa. Although treatment did not alter (P > .10) pregnancy rates, increasing the amount of alfalfa supported shorter intervals to conception (P = .03). Cows fed .96% BW alfalfa weaned heavier calves (quadratic, P = .04) than other groups. Results indicate that improvements in performance of beef cows in moderate body condition were greater when the amount of supplemental alfalfa was increased from .48 to .72% BW than when it was increased from .72 to .96% BW.(ABSTRACT TRUNCATED AT 250 WORDS)

Technical note: evaluation of acid detergent lignin, alkaline peroxide lignin, acid insoluble ash, and indigestible acid detergent fiber as internal markers for prediction of alfalfa, bromegrass, and prairie hay digestibility by beef steers.

Six steers (BW = 436 +/- 15 kg) were assigned randomly to alfalfa, bromegrass, or prairie hay diets in a replicated 3 x 3 Latin square design to evaluate the efficacy of different internal markers for estimating OM digestibility (OMD). Internal markers used to estimate OMD included ADL, alkaline peroxide lignin (APL), AIA, and indigestible ADF (IADF), which consisted of a 144-h in vitro incubation (IADFWOUT), indigestible ADF with acid/pepsin pretreatment of feed and orts samples (IADFFEED), or acid/pepsin pretreatment of feed, orts, and fecal samples (IADFALL). Marker-derived estimates of OMD were compared with OMD measured by total fecal collection (TFC). For the alfalfa diet, all marker estimates differed (P less than .05) from the TFC measurement; however, lignin-based procedures (ADL and APL) and IADF with acid/pepsin pretreatment (IADFFEED, IADFALL) were numerically closest to TFC values. Estimates of bromegrass and prairie hay OMD by ADL, APL, and AIA ratio were not different (P greater than .05) from TFC measurement, although AIA seemed to provide the most accurate estimate for prairie hay. All indigestible ADF procedures yielded estimates of forage OMD that differed (P less than .05) from TFC for all forages; acid/pepsin pretreatment of samples (IADFFEED and IADFALL) improved accuracy of the OMD estimates in all forages. Likewise, recovery of indigestible ADF was consistently least among the markers evaluated. These results indicate that APL ratio performed similarly to ADL ratio in estimating forage OMD, that AIA estimated grass OMD very accurately, and that estimation of OMD by indigestible ADF ratio was improved when the procedure was accompanied by an acid/pepsin pretreatment of samples.