Analysis for data-derived extrapolation factors for procymidone.

The derivation of Chemical Specific Adjustment Factors (CSAFs) (IPCS, 2005; U.S. EPA, 2014) depends on the choice of appropriate dose metric. EPA and IPCS guidance was applied to derive a CSAF for developmental toxicity for procymidone (PCM). Although kinetic data were not available in humans at any dose, sufficient toxicokinetic data are available in a surrogate species, primates, and from chimeric mice with both rat and human liver cells to offer insights. Alternative approaches were explored in the derivation of the CSAG based on review of the available kinetic data. The most likely dosimetric adjustment is the Cmax based on the character of the critical effect - reduced anogenital distance and increased incidence of hypospadias in male rats, which likely occurs during a small window of time during development of the rat fetus. Cmax is also the default dosimeter from U.S. EPA (1991). However, in this case, the use of Cmax is also likely more conservative than the use of area under the curve (AUC), which otherwise is the default recommendation of the IPCS (2005). Despite human data, estimated tentative CSAF value is 0.48 (range, 0.22 to 0.74). The use of any of these values would be supported by the available data.

A reproductive, developmental and neurobehavioral study following oral exposure of tetrabromobisphenol A on Sprague-Dawley rats.

The objectives of these GLP US EPA OPPTS 970.3800 and 970.3700 studies were to examine the effects of tetrabromobisphenol A (TBBPA) at oral doses of 10, 100 or 1000 mg/kg BW/day over the course of 2 generations on growth as well as behavioral, neurological and neuropathologic functions in offspring. In a separate study the influence of oral TBBPA (0, 100, 300 or 1000 mg/kg BW/d) was examined on embryonic/fetal development from gestation days (GDs) 0-19. In the reproductive study, exposure to ≥ 100-mg/kg BW/d TBBPA resulted in a decrease in circulating, peripheral thyroxine (T4) levels in rats that were not accompanied by any marked alterations in triiodothyronine (T3) and thyroid stimulating hormone (TSH). These findings are explainable on the basis of induction of rat liver catabolism, a phenomenon that may be species-specific and not relevant for humans. TBBPA at up to 1000 mg/kg BW/d was not associated with any significant non-neurological effects on reproduction, growth and development. A subtle reduction, of unknown biological relevance, in the thickness of the parietal cortices of 11-day-old F2 pups in the 1000 mg/kg BW/d group was noted. This change was not accompanied by evidence of micro-anatomic changes. No estrogenic effects sufficient to affect macro and micro anatomy, fertility, reproduction, development, survival or behavior were detected in the embryofetal development study or in the multigenerational study. No other TBBPA-related effects on developmental neurotoxicity/neuropathology were detected. In the developmental study no TBBPA related change in mortality rate was observed in any of the dams. No other significant test article-related effects were noted. The no observed effect level (NOEL) for maternal and developmental toxicity was 1000 mg/kg BW/d, the highest dose evaluated.

Determination of the anatomic communications among compartments within the carpus, metacarpophalangeal and metatarsophalangeal joints, stifle joint, and tarsus in llamas.

OBJECTIVE: To determine the anatomic communications among compartments within the carpus, metacarpophalangeal and metatarsophalangeal joints, stifle joint, and tarsus in llamas. SAMPLE POPULATION: 88 limbs from 22 llamas necropsied because of reasons unrelated to disease of the carpus; tarsus; or metacarpophalangeal, metatarsophalangeal, or stifle joints. PROCEDURE: 1 compartment (randomly assigned) of each joint was injected with blue latex solution. Communication between joint compartments was determined by observation of latex in adjacent compartments following frozen sectioning. RESULTS: Of the 44 carpi, 30 (68%) had anatomic separation between the radiocarpal and middle carpal joints, whereas the remaining 14 (32%) had communication between the radiocarpal and middle carpal joints. In the metacarpophalangeal or metatarsophalangeal joints, medial and lateral joint compartments remained separate in 83 of 88 (94%) joints injected. The tibiotarsal and proximal intertarsal joints communicated in all tarsi examined, whereas 14 of 38 (37%) communicated between the proximal intertarsal and distal intertarsal joints. Communication between the distal intertarsal and tarsometatarsal joints was detected in 17 of 25 (68%) specimens; all 4 tarsal joints communicated in 11 of 42 (26%) specimens examined. Examination of 33 stifle joints that were successfully injected revealed communication between the femoropatellar, medial femorotibial, and lateral femorotibial joints. CONCLUSIONS AND CLINICAL RELEVANCE: These data suggest that it is important to determine the joint communications specific to each llama prior to treatment of septic arthritis. The metacarpophalangeal or metatarsophalangeal joint compartments may be considered separate, although the lateral and medial compartments infrequently communicate along the proximal palmar or plantar aspect.

Exposure to soil contaminated with an environmental PCB/PCDD/PCDF mixture modulates ultraviolet radiation-induced non-melanoma skin carcinogenesis in the Crl:SKH1-hrBR hairless mouse.

Chlorinated aromatic contaminants are active in carcinogenic processes within the skin and may have the potential to modulate ultraviolet radiation (UV)-induced skin carcinogenesis. Exposure to a complex environmental PCB/PCDD/PCDF mixture (polychlorinated biphenyls/polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans) during the irradiation phase of photocarcinogenesis was associated with significant (P < or = 0.001) reductions in papilloma incidence and squamous cell carcinoma multiplicity at irradiated skin sites. This protective effect was associated with significantly (P < 0.0001) reduced chronic epidermal thickening in UV and contaminant-exposed mice compared with mice exposed to UV only. Contaminant exposure was also associated with increased UV absorbance of skin methanol extracts implying a sunscreen-like effect.

Toxic and feeding deterrent effects of native aquatic macrophytes on exotic grass carp (Ctenopharyngodon idella).

Declines of amphibians have been attributed to many factors including habitat degradation. The introduction of grass carp (Ctenopharyngodon idella) as a biological agent for aquatic plant control in ponds and lakes managed narrowly for human recreation has likely contributed to amphibian declines through massive plant removal and associated habitat simplification and thus degradation. This research examined the interactions among grass carp and three Midwestern aquatic plants (Jussiaea repens, Ranunculus longirostris, and R. flabellaris) that may be of value in rehabilitation of habitats needed by amphibians. The feeding preference study found that C. idella avoided eating both J. repens and R. longirostris. Ranunculus species studied to date contain a vesicant toxin called ranunculin that is released upon mastication. The study that compared the effects of R. flabellaris, J. repens and a control food administered by tube feeding to C. idella found significant lesions only in the mucosal epithelium of the individuals exposed to R.flabellaris. The avoidance by C. idella of J. repens and R. longirostris in the feeding preference study, and the significant toxicity of R. flabellaris demonstrated by the dosing study, indicate these plants warrant further examination as to their potential effectiveness in aquatic amphibian habitat rehabilitation.