Dear Sir, There is no other organ such as Lungs in any life form which has the most finest MICRO CIRCULATION where the EXCHANGE of the gases as per inhalation and exhalation occurs. So any toxin in blood when it reaches the lungs the alveolar structure or the air sacs arterioles and the venules go through a total structural and functional destruction and so is the damage to great extent  --- please remember one another organ also goes through STRUCTURAL AND FUNCTIONAL DAMAGE when UREA and URIC ACID and CREATININE level in the Blood rises --- can you guess----- the KIDNEYS. What I am trying to say is when it is Toxin then the damage is at the most sensitive and delicate part of the functional part of the organ which is always irreversible. Thanks for the opportunity to answer .

I agree with Dr. Hameed.  Also consider that acute lung injury can be inadvertently caused by non-toxic substances as well.  For instance, the patient who takes doxycycline on an empty stomach and then lies down to go to sleep can cause sever GERD followed w/ acidic vapors emanating from the esophagus and then "burning" the lungs during inhalation.  These patients may even present as if they have an aspiration pneumonia.  Some of these patients will have wheezing that does not respond to albuterol nebs and at times can even with time develop pulmonary fibrosis.  In other words, the agent, in this case doxycycline, was not necessarily directly toxic to the lung tissue but the end result was the same.

thank u dr. Hameed sir  for kind of consideration and wayne sir. i am new to  know this doxycycline related ALI 

I agree with all of the above. additionally, lungs are also a site of metabolism  of drugs the more metabolism is taken place in the lung the more the lung is affected. a good example are the lung of the ships please go into the literature for the differences.   

All of the above are true. The entire blood supply does through the lungs which can metabolize many compounds to more toxic intermediates through oxygen free radical formation. Examples are paraquat (as given above) and also bleomycin. Club cells in the pulmonary epithelium (previously called Clara cells) are implicated in this metabolic process.

thank you nahum sir and  mary mam, you are right as  some anticancer drugs like mustard derivatives and bleomycin mostaly affect lungs than spleen, liver, etc although liver would have been also affected by such toxin but due to higher detoxification (glutathione contents) system, liver  protect itself. moreover, fatty tissue have tendency to accumulate them. 

Far in the past ( ! ) I was involved in demonstrating that calcitonin, 1st thought as coming only from thyroid C-cells, was actually present in several other locations, and including the lung. Subsequently, in studying burn victims, the lung was soon shown to be critical to understanding outcomes, even when inhalation injury was inapparent, by usual criteria at the time, on admission. It's levels (and subsequently those of procalcitonin as well) correlated directly with mortality. After that, its source in the Pulmonary Neuroendocrine Cell (PnEC) of the airway was also confirmed. (See the work of Kenneth L. Becker, Adi Gazdar, and others with whom I worked at the time). Since other tissues contain neuroendocrine cells with calcitonin and other hormones, one can readily imagine that given the now more appreciated both endocrine, apocrine, but also paracrine effects locally, and related to initiating inflammation messaging, ... one "site" (perhaps injured) is soon "talking" to another. Per gram of tissue, the thyroid still contains the most immunocalcitonin at assay. But per organ or organ system, the lung and its PnEC is a most important reservoir. So include it in your thoughts as both target and initiator, as a function of the setting or variability in the stimulus of exposure. Not tacked down to one or the other. Then find an analogy in apoptosis: when is it needed, and when is it an error to have initiated it? Extremes of traumatic injury, as I witnessed in patients with large burns, can certainly overwhelm and "confuse" our response mechanisms. Burn size was found to be less predictive of mortality and eventual outcome, than what patients  had inhaled, and in so doing, exposing the PnEC. Think of the contact with flame on the outside (the skin burn), as you have been considering your various toxins and their effects. Quite local, like painting the cells with the poison. Certainly bad to come in contact with, and as a function of the dose or exposure: lethal. Include illnesses like pneumonia as the "medical equivalent" of traumatic inhalation injury, with bacteria also able to initiate the PnEC's response. But think as well of the neuroendocrine response, with global effects in the body, as the critical messenger, but also the very local director of response type and magnitude. Useful, I hope. All the best to you in your continued pursuits. 

I agree with all of the above. However, it is difficult to generalize for all or most of the compounds. Mechanism of pulmonary or lung toxicity differs with compound in question.  

This is an interesting question. Something to consider in answering it is the role  that toxicological interactions could have in lung injury, e.g., from one substance inhaled along with another substance administered via another route. For example (quoting from "The role of toxicological interactions in lung injury".publication I co-authored many years ago), "Damage of the alveolar zone (of mice) by the antioxidant butylated hydroxytoluene (BHT, administered ip) can be greatly enhanced by subsequent exposure to oxygen concentration which, otherwise, would have little if any demonstrable effect. The synergistic interaction between BHT and oxygen results in a resulting interstitial pulmonary fibrosis. Acute or chronic lung disease may then be caused not only by one agent, but very likely in many instances by the interaction of several agents." Free full text is available via the second link. [Disclaimer: Opinion is my own and not necessarily that of NIH/NLM.]

http://www.ncbi.nlm.nih.gov/pubmed/6376096

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1568374/

Yes, trans-dermal! years ago, dermatologist Dr Don Rosenthal and I published a case report in which a 30+ year old farmers wife had mixed a herbicide (Paraquat) to spray their fruit trees. She did not take the advised precautions to wear a total covering. She had a scratch on her forearm prior to mixing the Paraquat which subsequently became necrotic and she simultaneously, over about 2-3 weeks developed respiratory failure due to a rapidly developing neutrophilic inflammatory response and ARDS from which she died in about 3 weeks. Since her husband did the spraying her only exposure was dermal!

Dear Dr. Newhouse, Thanks for providing very important and useful information. This observation is in agreement with my theoretical knowledge about Paraquat. Presently, we are investigating the effect of percutaneous application of Sulphur mustard  or mustard gas (HD) on respiratory system with special reference to bronchial alveolar lavage fluid (BALF). Preliminary results have indicated that HD has toxic effect on tracheo-bronchial tree even when applied on closely hair-clipped intact skin of Swiss mice. However, chances of inhalation of evaporated HD had been ruled out.    

Thank you Dr. Newhouse, and Dr. Praveen sir for considering me and sharing your valuable views. somehow it has also been considered  due to  anatomy and physiology of pulmonary system that is highly vascular and  Moreover at particular time point lungs is highest blood supplied organ than other. Although mechanism of toxicity for different kinds of things is differ, but accumulation of these toxin  through blood, in particular to lungs reflect the results of physiology of lungs.