Toxicology Sample Clauses
The Toxicology clause outlines the requirements and procedures related to the assessment of potential toxic effects of substances, products, or materials involved in the agreement. Typically, this clause specifies the standards for toxicological testing, the responsibilities for conducting such tests, and the reporting of results to relevant parties. For example, it may require that all chemical components be evaluated for safety before use or distribution. The core function of this clause is to ensure that all parties are aware of and comply with safety standards, thereby minimizing health risks and legal liabilities associated with toxic substances.
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Toxicology a. The ingredients in the formulated product do not pose a significant risk to human or animal health.
i. No ingredient in the formulated product is a known or presumed carcinogen, mutagen, teratogen, endocrine disruptor, reproductive toxin, or neurotoxin, according to conclusions of any of the following leading regulatory bodies: United States Environmental Protection Agency (“EPA”), Canadian Pest Management Regulatory Agency (“PMRA”), Australian Pesticides and Veterinary Medicines Authority (“APVMA”); European Food Safety Authority (“EFSA”); European Chemicals Agency (“EChA”).
ii. No ingredient in the formulated product is included on Annex III of the Rotterdam Convention (PIC list) or listed in the Stockholm Convention.
b. The formulated product does not pose a significant acute toxicity/irritation hazard and has no novel acute toxicological effects.
i. Formulated product must be EPA category III or IV for acute oral, dermal and inhalation toxicity and eye/skin irritation (a maximum of ‘CAUTION’ signal word in the US). For countries outside the US, may not be classified in acute toxicity categories 1-4 for acute oral, dermal and inhalation toxicity under the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) (i.e., must be GHS Categories 5, with maximum ‘WARNING’ signal word based on acute toxicity) and may not be not be classified as skin corrosive or eye/skin irritant.
Toxicology. 1. Collect required toxicological samples
Toxicology. The draft report for TOX142 “A Study of the Effects of Orally Administered TP-0239 on Pre- and Postnatal Development, Including Maternal Function, in the Rat” is due Sept. 23, 2003. The date for delivery of the final report is targeted for November 1, 2003.
Toxicology. An inventory of archived tissues and samples for each of the completed toxicology studies is included in the final study report for each study. Transfer of the storage of these samples to Bukwang needs to be discussed. • Additional samples located at Triangle include: • Thirty-two wet tissues to Trump’s fixative for electron microscopy from study TOX045 from Week 119 (one female sacrificed moribund) and from Week 148 (3 females and 4 males, control and high dose). There are 4 tissues from each animal - heart, kidney, liver, and skeletal muscle. • Photomicrographs of liver, heart, and skeletal muscle and negatives of same; lepon blocks; glass slides; and 44 vials of heart, muscle, kidney, and liver (in formalin) from the woodchuck study 98-11-A conducted by Cornell. The 44 vials contain huge chunks of issue that would not have fixed well and were removed from dead animals, and therefore may have been subject to significant autolysis. • Another set of positives (slides) and photographs taken during examination by light microscopy of skeletal muscle (myopathy) from selected monkeys from study TOX045.
Toxicology. MIRV was evaluated for toxicity after a single IV injection in cross-reactive (monkey) and non- cross-reactive (mouse) species. Results of these studies supported the first-in-human (FIH) study exploring the safety and tolerability of MIRV when administered once every 3 weeks to patients with advanced solid tumors. Potential risks suggested by these studies as well as clinical experience with other maytansinoid ADCs include hematologic abnormalities, electrolyte alterations, injection site reactions, infusion reactions, immunogenicity, hepatic abnormalities, and peripheral neuropathy. Toxicology studies are further detailed in the Investigator Brochure.
Toxicology. In preparation for the initial IND filing, Licensee will contract with qualified CRO(s) to perform oral rat and dog rising single dose + 7-day repeated-dose range-finding toxicity studies with toxicokinetics and oral rat and dog 28-day repeated-dose toxicity studies with toxicokinetics. Additionally, Licensee will contract out the performance of a standard battery of GLP genotoxicity studies, including in vitro bacterial reverse mutation test, in vitro mouse lymphoma thymidine kinase assay, and in vivo rat micronucleus test. Also, to support the single IV dose of MRI-1867 in the initial Phase I trial to determine absolute bioavailability, Licensee will contract out the performance of an in vitro hemolysis assay and an IV single species single dose local tolerance study. To support subsequent clinical trials and eventual marketing, Licensee will contract out the performance of oral rat 3-month and 6-month repeated-dose toxicity studies, oral dog 3-month and 9-month repeated-dose toxicity studies, carcinogenicity studies, and reproductive and developmental toxicity studies. Overall, the timeline and cost to complete the IND-enabling nonclinical studies is estimated at approximately[ ] and [ ]. Licensee will contract out clinical trial related tasks to qualified CRO(s). The initial trial (i.e., the protocol to be included in the original IND filing) is anticipated to be a Phase 1 safety, tolerability, and PK study in healthy volunteers. The study will include a single IV and oral dose to determine absolute bioavailability, followed by 28-days of oral dosing. During the latter part of the conduct of this trial, Licensee plans to contract out a Phase 1 clinical mass balance study (single oral dose of radiolabeled drug). This will allow for an early determination of relevant PK metabolites and parameters to follow in subsequent trials. Additionally, Licensee plans to collaborate with NIH to perform a Phase 1 study of MRI-1867 binding to CB1R in the brain (via positron emission tomography scanning). A-034-2016 NIH Patent License Agreement—Exclusive Following the completion of the Phase 1 safety, tolerability, and PK study in healthy volunteers, Licenseeplans to move to a Phase 1 safety, tolerance, PK, and PD study in patients with systemic sclerosis. This trial will include [ ] of oral dosing. Pending no safety concerns, Licensee plans to move to a Phase 2 safety, PK, and proof of concept trial in systemic sclerosis patients that is anticipated to include [ ] of ...
Toxicology. In preparation for the initial IND filing, Scopus Biopharma will contract with qualified CRO(s) to perform sc rat and dog rising single dose + 7-day repeated-dose range-finding toxicity studies with toxicokinetics and sc rat and dog 28-day repeated-dose toxicity studies with toxicokinetics. Scopus Biopharma will contract out the performance of an in vitro hemolysis assay and an IV two species, single dose local tolerance study. Scopus Biopharma will contract out clinical trial related tasks to qualified CRO(s). The initial trial (i.e., the protocol to be included in the original IND filing) is anticipated to be a Phase 1 open label dose escalation study of safety tolerance PK including bioavailability in healthy volunteers, (non-visceral injection SB-001FCDP vs comparator) to be followed by an IV version of the same study. Following the completion of two Phase 1 safety, tolerability, and PK studies in healthy volunteers, Scopus Biopharma plans to move to a Phase 2 randomized double-blind study of tolerance including dose response, safety and PK in patients (non-visceral injection SB-001FCDP vs comparator). Following the successful completion of the Phase 2 study, Scopus Biopharma intends to enter into two pivotal Phase 3 trials randomized double-blind study of efficacy, safety and population PK in patients (non-visceral injection SB-001FCDP vs comparator).
Toxicology. Binding and functional data demonstrated Rhesus or Cynomolgus monkeys to be relevant species to evaluate the safety of NI-0501. No off-target toxicity was attributed to the drug when administered to Cynomolgus monkeys in 13 weekly doses of up to 200 mg/kg. An enhanced susceptibility to infections due to an exaggerated pharmacological effect of the drug has been observed at all dose levels in animals originally harbouring gastrointestinal pathogens (Shigella, Salmonella, Campylobacter) prior to NI-0501 administration. In a second study, where Cynomolgus monkeys were not initially found to be harbouring gastrointestinal pathogens, weekly administrations of NI-0501 for 8 consecutive weeks at doses up to 30 mg/kg were well tolerated, without the need for antibiotic prophylaxis. Results from a human tissue cross-reactivity study, involving a panel of 35 different human tissues, demonstrated that NI-0501 did not cross-react with any of the human samples tested.
Toxicology. LDH, Grant
Toxicology. Maximum tolerated, single IV dose escalation studies of ETX2514 performed in rats and dogs did not result in serious test article–related events. Exposure across the dose ranges evaluated were generally dose proportional, and there were no significant differences between males and females. • 7-day IV repeat-dose range-finding studies in rats and dogs at doses up to the limit dose of 2000 mg/kg/day did not identify serious test article–related findings. • In pivotal 14-day IV repeat-dose toxicity studies conducted in rats and dogs, ETX2514 administered up to the limit dose of 2000 mg/kg/day was not associated with mortality or significant changes in clinical signs, ophthalmology, urinalysis or hematology parameters, organ weight changes, or changes in gross pathology or histopathology, and there were no toxicologically significant changes in clinical chemistry parameters. Based on these findings, the no-observed-adverse-effect-level (NOAEL) was 2000 mg/kg/day in both species. The associated combined-sex mean steady state maximum plasma concentration (Cmax) and AUC from 0 to 24 hours postdose (AUC0-24) values on Day 14 in the most sensitive species, rat, at the NOAEL were 1340 µg/mL and 3140 µg⋅h/mL, respectively. The exposure margin based on AUC0-24 relative to human exposures was 6.3-fold. • In a 7-day IV repeat-dose study of ETX2514 in combination with sulbactam, minimal decreases in body weight gain were noted, and there were no adverse effects on clinical pathology parameters, organ weights, or macroscopic tissue findings. Based on the mild severity of the findings, the NOAEL was the highest combination dose tested, 400 mg/kg/day of each compound. • The toxicity of ETX2514 alone or in combination with sulbactam was evaluated in a pivotal (Good Laboratory Practice [GLP]) study in rats administered the treatments IV daily for 28 days. ETX2514 administered alone (600 mg/kg/day) was devoid of toxicity. Notable effects in rats treated with the combination of sulbactam/ETX2514 (300 or 600 mg/kg/day of each compound) were consistent with known, monitorable effects of sulbactam. Dose-related inflammatory changes noted microscopically at the infusion site and in liver and lung with both combination doses were considered adverse effects of treatment; however, inflammatory changes in liver and lung were not associated with necrosis and were not present at the end of the recovery period. Thus, while there was no NOAEL identified in the study due to inflammatory cha...