Target Organ Toxicity in Rats After Subchronic Oral Exposure to Soil Extracts Containing a Complex Mixture of Contaminants.

Complex mixtures of unknown contaminants present a challenge to identify toxicological risks without using large numbers of animals and labor-intensive screens of all organs. This study examined soil extracts from a legacy-contaminated pesticide packaging and blending site. HepG2 cytotoxicity was used as an initial screen of 18 soil samples; then, three extracts (A, B and C) from different locations at the study site were used for testing in animals. The first two extracts were identified as the most toxic in vitro, and the latter extract obtained from a location further from these two toxic sampling sites. Then, target organ toxicities were identified following biweekly oral gavage for one month of three soil extracts (0.1% in polyethylene glycol or PEG) compared to vehicle control in male Sprague-Dawley rats (n = 9-10/group). Exposure to extract A significantly increased neutrophils and lymphocytes compared to control. In contrast, all extracts increased plasma α-2 macroglobulin and caused mild-to-moderate lymphocytic proliferation within the spleen white pulp, all indicative of inflammation. Rats exposed to all soil extracts exhibited acute tubular necrosis. Cholinesterase activity was significantly reduced in plasma, but not brain, after exposure to extract A compared to control. Increased hepatic ethoxyresorufin-o-deethylase activity compared to control was observed following exposure to extracts A and B. Exposure to soil extract C in rats showed a prolonged QTc interval in electrocardiography as well as increased brain lipid peroxidation. Candidate contaminants are organochlorine, organophosphate/carbamate pesticides or metabolites. Overall, HepG2 cytotoxicity did not successfully predict the neurotoxicity and cardiotoxicity observed with extract C but was more successful with suspected hydrocarbon toxicities in extracts A and B. Caution should be taken when extrapolating the observation of no effects from in vitro cell culture to in vivo toxicity, and better cell culture lines or assays should be explored.

Objective measures of laryngeal function after reinnervation of the anterior and posterior recurrent laryngeal nerve branches.

Previous research indicates that separate reinnervation of the anterior and posterior branches of the recurrent laryngeal nerve (RLN) can provide purposeful motion of the larynx, even after transplantation. This canine study was undertaken to better determine the results of RLN reinnervation after nerve transection distal to its bifurcation. This approximates ideal conditions for transplantation, because potential rejection and nerve branch mismatch are eliminated. Eight months after nerve repair, video, electromyographic, mechanical, and histologic data were collected on four canines. Results show return of appropriate motion without synkinesis, including purposeful abduction on endotracheal tube occlusion. Abductory function was weaker on the reinnervated side, but adduction was equal or stronger on the reinnervated vocal cord. These results indicate that this method of RLN reinnervation produces consistent, strong physiologic motion in the denervated larynx.