A proposal has been developed by the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) for an improved approach to assessing the safety of crop protection chemicals. The goal is to ensure that studies are scientifically appropriate and necessary without being redundant, and that tests emphasize toxicological endpoints and exposure durations that are relevant for risk assessment. The ACSA Life Stages Task Force proposes a tiered approach to toxicity testing that assesses a compound's potential to cause adverse effects on reproduction, and that assesses the nature and severity of effects during development and adolescence, with consideration of the sensitivity of the elderly. While incorporating many features from current guideline studies, the proposed approach includes a novel rat reproduction and developmental study with enhanced endpoints and a rabbit development study. All available data, including toxicokinetics, ADME data, and systemic toxicity information, are considered in the design and interpretation of studies. Compared to existing testing strategies, the proposed approach uses fewer animals, provides information on the young animal, and includes an estimation of human exposure potential for making decisions about the extent of testing required.

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The normal postnatal development of the canine kidney was investigated utilizing qualitative and quantitative histologic methods. Kidneys were examined at 2, 4, 8, 14, 22, 70, and 200 days of age. A subcapsular nephrogenic zone was present in the kidneys until approximately eight days of age. This zone contained tissues which interacted to produce new nephrons and interstitial tissues. Several developmental stages of forming nephrons were identified in this zone. Beneath the nephrogenic zone, renal corpuscles of increasing maturity were located at successively deeper cortical levels. The total number of nephrons was estimated to be 445,000 per kidney. This number did not vary significantly during growth. The corpuscular volume per nephron increased 249% from 14 to 200 days of age. During the same period there was a 303% increase in the tubular volume per nephron. Although the developing kidney differed anatomically from the adult kidney, the individual nephrons maintained volumetric corpuscular-tubular balance during growth.

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Ventricular candidiasis was the apparent cause of death in 14 of 21 captive birds, and incriminated in six others. No clinical signs were recognized in 14 of the 21 birds prior to death, and in four of the 21, no other gross or microscopic lesions were documented. Microscopic lesions included colonization of the koilin layer of the ventriculi by fungi with occasional penetration into the glandular epithelium. No conclusive pattern of infection by family of birds was detected.

Sulfuryl fluoride (SO(2)F(2)) is a structural fumigant gas used to control drywood termites and wood-boring beetles. The pharmacokinetics and metabolism of inhaled SO(2)F(2) were evaluated in male Fischer-344 rats exposed to 30 or 300 ppm (35)S-labeled SO(2)F(2) for 4 h. Blood, urine and feces were collected during and after the exposures and analyzed for radioactivity, (35)S-labeled fluorosulfate and sulfate, and fluoride (urine and feces only). Selected tissues were collected 7 days post-exposure and analyzed for radioactivity. During and after unlabeled SO(2)F(2) exposures, blood, brain, and kidney were collected and analyzed for fluoride ion. SO(2)F(2) was rapidly absorbed, achieving maximum concentrations of radioactivity in both plasma and red blood cells (RBC) near the end of the 4-h exposure period. Radioactivity was rapidly excreted, mostly via the urine. Seven days post-exposure, small amounts of radioactivity were distributed among several tissues, with the highest concentration detected in respiratory tissues. Radioactivity associated with the RBC remained elevated 7 days post-exposure, and highly perfused tissues had higher levels of radioactivity than other non-respiratory tissues. Radioactivity cleared from plasma and RBC with initial half-lives of 2.5 h after 30 ppm and 1-2.5 h after 300 ppm exposures. The terminal half-life of radioactivity was 2.5-fold longer in RBC than plasma. Based on the radiochemical profiles, there was no evidence of parent (35)SO(2)F(2) in blood. Identification of fluorosulfate and sulfate in blood and urine suggests that SO(2)F(2) is hydrolyzed to fluorosulfate, with release of fluoride, followed by further hydrolysis to sulfate and release of the remaining fluoride.