Chicken egg fetal liver DNA and histopathologic effects of structurally diverse carcinogens and non-carcinogens.

Chicken egg fetal livers were evaluated for histopathological changes produced by four genotoxic hepatocarcinogens: 2-acetylaminofluorene (AAF), aflatoxin B1 (AFB1), benzo[a]pyrene (BaP), diethylnitrosamine (DEN); four structurally related non- or weakly- carcinogenic comparators: fluorene (FLU), aflatoxin B2 (AFB2), benzo[e]pyrene (BeP), N-nitrosodiethanolamine (NDELA); two epigenetic hepatocarcinogens: clofibric acid (CFA), phenobarbital (PB); and the non-carcinogen, D-mannitol (MAN). CFA, PB and MAN were also assessed for formation of DNA adducts using the 32P nucleotide postlabeling (NPL) assay and for DNA breaks using the comet assay. CFA was also assessed in enhanced comet assay for oxidative DNA damage induction. Eggs were dosed on days 9- 11 of incubation. For genotoxicity evaluation, livers were collected 3h after the last dose. Liver qualitative histopathology assessment was performed on days 12 and 18 of incubation. CFA was negative for DNA adducts but yielded clear evidence of DNA breaks due to oxidative stress. PB and MAN produced no DNA adducts or breaks. Liver to body weight ratios were not affected in most groups, but were decreased in DEN groups, and increased after PB dosing. Livers from control groups, FLU, AFB2, BeP, NDELA, CFA, and MAN groups, displayed a typical hepatocellular trabecular pattern at both time points. In contrast, the four genotoxic carcinogens induced time- and dose- related interference with fetal liver cell processes of proliferation, migration and differentiation, leading to hepatocellular and cholangiocellular pleomorphic dysplasia and re-(de-) differentiation with distortion of the trabecular pattern. In addition, dosing with the high dose of DEN produced gallbladder agenesis. PB induced hepatocellular hypertrophy, interference with migration, expressed as distortion of the trabecular pattern, and a moderate cholangiocellular dysplasia. In summary, histopathological analysis of chicken fetal livers revealed developmental anomalies, as well as genotoxicity-induced and, in the case of PB, adaptive morphological changes. Thus, the model provides histopathological outcomes of molecular effects.

Lessons to be learned from an analysis of ammonium nitrate disasters in the last 100 years.

Process safety, as well as the safe storage and transportation of hazardous or reactive chemicals, has been a topic of increasing interest in the last few decades. The increased interest in improving the safety of operations has been driven largely by a series of recent catastrophes that have occurred in the United States and the rest of the world. A continuous review of past incidents and disasters to look for common causes and lessons is an essential component to any process safety and loss prevention program. While analyzing the causes of an accident cannot prevent that accident from occurring, learning from it can help to prevent future incidents. The objective of this article is to review a selection of major incidents involving ammonium nitrate in the last century to identify common causes and lessons that can be gleaned from these incidents in the hopes of preventing future disasters. Ammonium nitrate has been involved in dozens of major incidents in the last century, so a subset of major incidents were chosen for discussion for the sake of brevity. Twelve incidents are reviewed and ten lessons from these incidents are discussed.

Study on the variation rules of the joint effects for multicomponent mixtures containing cyanogenic toxicants and aldehydes based on the transition state theory.

Although the study of the variation rules of the joint effects for multicomponent mixtures has gained increasing attention, it still remains unclear how the variation occurs and what the relationships between the joint effects of multicomponent mixtures and their corresponding binary mixtures are. To explain how the variation occurs, this study first proposes a hypothesis on the variation rules of the joint effects using the well-known transition state theory. The hypothesis concluded that the joint effect of multicomponent mixtures is among the joint effects of the corresponding binary mixtures. This hypothesis was named the fishing hypothesis because there is a similarity between the action process of the joint effects and the fishing process. Next, the hypothesis was validated by use of the experimental data by evaluating the joint effects of binary, ternary and quaternary mixtures containing cyanogenic toxicants and aldehydes on Photobacterium phosphoreum. The application of the fishing hypothesis can explain the rule as to how the joint effects of a multicomponent-mixture vary with its number of components and their ratios. This study provides a good method to predict the joint effects of multicomponent mixtures using the joint effects of their corresponding binary mixtures. An improvement in the fishing hypothesis will be needed in our future studies due to the approximate assumptions used in the deduction of the hypothesis.