Terpenes and terpenoids in chemical sensitivity.

UNLABELLED: CONTEXT : Terpenes and terpenoids are a diverse class of organic compounds produced by a variety of plants, particularly conifers. Chemically sensitive patients can be targeted by terpenes and terpenoids, resulting in a triggering of symptoms and pathology. Often patients cannot clear their symptoms from exposure to chemicals unless terpenes and terpenoids are avoided and neutralized along with chemical avoidance and treatment. OBJECTIVE: This article evaluates the presence, diagnosis, and treatment of terpenes exposure in chemically sensitive patients. DESIGN: A double-blind, placebo-controlled, 2-part study was designed to establish the chemically sensitive state of the patients in part 1, followed by a second set of challenges to determine each patient's concurrent sensitivity to terpenes and terpenoids in part 2. In all of the challenges, normal saline was used as a control. A case report illustrates the history of 1 patient and describes the authors' treatment methods. SETTING: The study was developed and conducted at the Environmental Health Center of Dallas (EHC-D) because the environment within the center is 5 times less polluted than the surrounding environments, as determined by quantitative air analysis and particulate counts. PARTICIPANTS: A total of 45 chemically sensitive patients at EHC-D with odor sensitivity to terpenes. The cohort included 18 males and 27 females, aged 24-62 y.Intervention • Patients were deadapted (4 d) and evaluated in a 5-times-less-polluted environment, which was evaluated using air analysis and particulate counts. After deadaptation, the patients were challenged by inhalation in a controlled, less-polluted glass steel booth inside an environmentally controlled room with an ambient air dose of the toxics in the order of parts per billion (PPB) and parts per million (PPM). These toxics included formaldehyde, pesticide, cigarette smoke, ethanol, phenol, chlorine, new sprint, perfume, and placebo. They were also challenged intradermally with extracts of volatile organic compounds (VOCs), including formaldehyde, orris root, ethanol, phenol, cigarette smoke, chlorine, newsprint, perfume, terpenes, terpenoids, and placebo. OUTCOME MEASURES: Inhaled challenges recorded pulse, blood pressure, peak bronchial flow, and other signs and symptoms 30 min before and at 15-min intervals for 2 h postchallenge. Intradermal challenges recorded wheal size and the provocation of signs and symptoms. RESULTS : Different numbers of patients were tested for each terpenes source because of time-related factors or the cumulative effect of testing, which made patients unable to continue. Of 45 chemically sensitive patients in the study, 43 demonstrated sensitivity to terpenes. CONCLUSIONS: This particular patient group was positive for a number of toxic and nontoxic chemicals provoking their symptoms. This study shows there was a connection between VOCs, other chemicals, and terpenes in chemically sensitive patients in a prospective cohort study. It has also shown the potential for terpenes to exacerbate symptoms of chemical sensitivity. Further research on this topic is recommended.

A rare case of toxic optic neuropathy secondary to consumption of neem oil.

A 35-year-old female was referred to our hospital with bilateral loss of vision of two days duration. She gave history of consumption of about 150 ml of neem oil five days back.Examination revealed no perception of light in both eyes. Both pupils were dilated and sluggishly reacting to light. Her fundus examination showed bilateral hyperemic, edematous discs and also edema extending along the superior and inferior temporal vascular arcade. Magnetic resonance imaging (MRI) scan showed bilateral putaminal regions with altered signal, hypointensities in T1-weighted images, hyperintensities on T2-weighted, images and hyperintense on Fluid Attenuation Inversion Recovery (FLAIR) images suggestive of cytotoxic edema due to tissue hypoxia. Her vision improved to 20/200 in both eyes with treatment after two months. This is the first case report of such nature in the literature to the best of our knowledge.

"Herbal remedy is natural and safe"--truth or myth?

Neem oil is often used externally as a traditional medicine in India. Its ingestion, even in small doses produces toxic effects like severe metabolic acidosis, seizures, renal failure and encephalopathy. Management is supportive and prognosis is generally good but fatalities may occur. Herein we report an unusual case of neem oil toxicity in a previously normal adult.

Neem oil poisoning.

We report an unusual case of neem oil poisoning in a previously normal 5 year old child. The child presented with refractory seizures and was having metabolic acidosis. Late neurological sequelae in the form of auditory and visual disturbances, and ataxia were present.

Management of root lesion nematode, Pratylenchus delattrei in crossandra using oil cakes.

Selected oil cakes, neem, castor and mahua, were tried independently and in combination with a chemical nematicide (carbofuran 3G) for the management of Pratylenchus delattrei in crossandra under glass house conditions. The neem oil cake was effective compared to other oil cakes used and there was a synergistic effect when the neemcake was coupled with carbofuran 3G in the management of Pratylenchus delattrei. The treatment resulted in better establishment of seedlings, and with increased plant bio-mass and flower yield.

Fatal large-volume mouthwash ingestion in an adult: a review and the possible role of phenolic compound toxicity.

OBJECTIVE: To describe a case of fatal mouthwash ingestion and review possible sources of toxicity. DESIGN: Case report. SETTING: Veterans Administration Medical Center. PATIENT: Single patient with massive mouthwash ingestion. MAIN RESULTS: This patient was a 45-year-old man who developed cardiovascular collapse and multiorgan system failure following a massive ingestion of mouthwash (almost 3 liters). His presentation was remarkable for a profound anion-gap metabolic acidosis and a significant osmolar gap. No other co-ingestants were identified, and he expired despite full supportive care including dialysis and mechanical ventilation. An autopsy failed to identify any other cause of death. Nonalcoholic ingredients of this mouthwash are phenolic compounds (eucalyptol, menthol, and thymol), and large-volume mouthwash ingestion will produce exposure in the reported toxic range of these ingredients. CONCLUSIONS: When ingested in large quantities, the phenolic compounds in mouthwash may contribute to a severe anion-gap metabolic acidosis and osmolar gap, multiorgan system failure, and death. These compounds, in addition to alcohol, may account for the adverse effects associated with massive mouthwash ingestion.

Reactions among indoor pollutants.

This paper reviews recent studies in the field of "indoor chemistry"--reactions among indoor pollutants. Advances have occurred in a number of areas. A mouse bioassay procedure has shown that ozone/terpene reactions produce products that are more irritating than their precursors, although the agents responsible for the deleterious effects remain to be determined. Indoor ozone/terpene reactions have been demonstrated to produce hydroxyl radicals, hydrogen peroxide, sub-micron particles, and ultrafine particles. New analytical techniques such as LC/MS and thermal desorption mass spectrometry have greatly improved our knowledge of the condensed-phase species associated with such particles. Indeed, the latter approach has identified a number of short-lived or thermally labile species, including organic hydroperoxides, peroxy-hemiacetals, and secondary ozonides, which would be missed by more conventional techniques. Investigators are making inroads into the poorly understood area of indoor heterogeneous chemistry. Systems studied include ozone/HVAC components, ozone/paint, and ozone/carpets. Another heterogeneous process that has been further examined is the indoor formation of nitrous acid through NO2/surface chemistry. Emissions from indoor sources that contribute to, or are altered by, indoor chemistry have also received attention. Researchers have expanded our awareness of reactive chemicals that can emanate from wood coatings and other products commonly used indoors. In a related vein, a number of recent investigations have shown that emissions from materials can be significantly altered by indoor chemistry. On the theoretical side, an outdoor atmospheric chemistry model has been modified for use as an indoor air model, the effects of ventilation rates on indoor chemistry have been simulated, and initial steps have been taken in applying computational fluid dynamics (CFD) methods to indoor chemistry.

A fatality due to accidental PineSol ingestion.

The case history and toxicological findings of a fatal PineSol intoxication are presented. An 89-year-old white female with Alzheimer's disease accidentally drank PineSol and was subsequently brought to the hospital where she was pronounced dead on arrival. Significant autopsy findings included acute erosive gastritis. There appeared to be no aspiration of PineSol into the lungs. Isopropanol along with 1-alpha-terpineol are the two major toxic ingredients of PineSol. The toxicological screening and quantitiation of 1-alpha-terpineol in postmortem fluids was performed by gas chromatography-mass spectrometry using a simple one-step extraction. Postmortem blood, urine, and gastric levels of 1-alpha-terpineol were 11.2 mg/L, 5.76 mg/L, and 15.3 g/L, respectively. Postmortem blood, vitreous humor, urine, and gastric acetone concentrations were 25, 31, 33, and 28 mg/dL. Postmortem concentrations of isopropanol were less than 10 mg/dL in the blood, vitreous humor, urine, and gastric contents. The cause of death was ruled acute 1-alpha-terpineol intoxication due to accidental ingestion of PineSol, presumably caused by confusion related to Alzheimer's disease.

[An experimental validation of the maximum permissible concentration of a mixture of mono- and bicyclic terpenoid alcohols in water]. / Eksperimental'noe obosnovanie predel'no dopustimoi kontsentratsii smesi mono- i bitsiklicheskikh terpenoidnykh spirtov v vode.

The maximum permissible concentrations (MPC) of Viterol in water were established, which was equal to 0.14 mg/l. Its organoleptic and general sanitary thresholds were determined at the same level.

Neonatal Clara cell toxicity by 4-ipomeanol alters bronchiolar organization in adult rabbits.

Nonciliated bronchiolar (Clara) cells metabolize environmental toxicants, are progenitor cells during development, and differentiate postnatally. Because differentiating Clara cells of neonatal rabbits are injured at lower doses by the cytochrome P-450-activated cytotoxicant 4-ipomeanol than are those of adults, the impact of early injury on the bronchiolar epithelial organization of adults was defined by treating neonates (3-21 days) and examining them at 4-6 wk. Bronchiolar epithelium of 6-wk-old animals treated on day 7 was most altered from that of control animals. Almost 100% of the bronchioles were lined by zones of squamous epithelial cells. Compared with control animals, the distal bronchiolar epithelium of 4-ipomeanol-treated animals had more squamous cells (70-90 vs. 0%) with a reduced overall epithelial thickness (25% of control value), fewer ciliated cells (0 vs. 10-20%), a reduced expression of Clara cell markers of differentiation (cytochrome P-4502B, NADPH reductase, and 10-kDa protein), and undifferentiated nonciliated cuboidal cell ultrastructure. We conclude that early injury to differentiating rabbit Clara cells by a cytochrome P-450-mediated toxicant inhibits bronchiolar epithelial differentiation and greatly affects repair.

Multiple organ failure after ingestion of pennyroyal oil from herbal tea in two infants.

BACKGROUND: Hepatic and neurologic injury developed in two infants after ingestion of mint tea. Examination of the mint plants, from which the teas were brewed, indicated that they contained the toxic agent pennyroyal oil. METHODS: Sera from each infant were analyzed for the toxic constituents of pennyroyal oil, including pulegone and its metabolite menthofuran. RESULTS: Fulminant liver failure with cerebral edema and necrosis developed in the first infant, who died. This infant was positive only for menthofuran (10 ng/mL). In the other infant, who was positive for both pulegone (25 ng/mL) and menthofuran (41 ng/mL), hepatic dysfunction and a severe epileptic encephalopathy developed. CONCLUSION: Pennyroyal oil is a highly toxic agent that may cause both hepatic and neurologic injury if ingested. A potential source of pennyroyal oil is certain mint teas mistakenly used as home remedies to treat minor ailments and colic in infants. Physicians should consider pennyroyal oil poisoning as a possible cause of hepatic and neurologic injury in infants, particularly if the infants may have been given home-brewed mint teas.

Status spongiosis, optic neuropathy, and retinal degeneration in Helichrysum argyrosphaerum poisoning in sheep and a goat.

Lesions of natural Helichrysum argyrosphaerum poisoning were studied in eight sheep and one goat. Light microscopic examination revealed widespread, bilaterally symmetrical status spongiosis of the white matter of the brain consistently present in the subependymal area adjacent to the lateral ventricles, cerebellar peduncles, and brain stem in all animals. In three animals, the ultrastructural finding of intramyelinic vacuolation due to splitting of the myelin lamellae at the intraperiod lines indicated myelin edema. There was also mild distension of perivascular and extracellular spaces in the severely affected areas. Significant changes were absent in neurons, glial cells, axons, or blood vessel walls. Myelin edema associated with degeneration and loss of axons and myelin and astrocytic gliosis was present in the intraorbital and intracranial portions of the optic nerves. In the intracanalicular portions of the nerves in three animals that were studied, more chronic lesions consisting of fibrosis and atrophy of the nerve suggested that the optic neuropathy follows compression of the nerve in the optic canal as a result of myelin edema. The toxic principle of the plant also caused a degenerative retinopathy in five animals. The essential histopathologic change was degeneration and loss of the photoreceptor outer segments predominantly in the nontapetal retina. These retinal lesions were associated with hyperplasia and hypertrophy and with migration of the pigmented epithelium, focal retinal separation, and depletion and loss of the nuclear layers.

[Fatal poisoning caused by oil of epazote, Chenopodium graveolens]. / Envenenamiento mortal causado por el aceite de epazote, Chenopodium graveolens.

We present a case of acute lethal poisoning by oil of "epazote" (oil of chenopodium), in a 2 y 9 m female. The volatile oil was administered according to the advice of a "curandera" (female healer), in a total quantity of 40 ml. Clinical features of the poisoning were: vomiting, deep coma, seizures, mydriasis, apnea, metabolic acidosis, neurogenic shock and death. The EEG suggested a diffuse encephalopathy, the CT scan with an image of severe brain edema and ventricular collapse. Relevant postmortem findings were brain edema and neuronal necrosis, pneumonia, enteritis, pericholangitis, mild pancreatitis and tubular necrosis. The phytochemical analysis of volatile oil identified ascaridol, the main active compound of the chenopodium herbs, in a quantity of 39 mg/ml (1,560 mg in the dose administered), and Chenopodium graveolens as the plant employed to prepare it. According to the age of the patient, 60 mg of ascaridol would be the recommended dose formerly used in the treatment of parasitic disease. Thus 1,560 mg was 26 times higher than the recommended dose, and exceeded by 56% the dose of 1,000 mg reported as lethal in humans.

[Development of immune response to the combined action of hepatotropic poisons and high ambient temperature]. / Razvitie immunnogo otveta pri sochetannom deistvii na organizm gepatotropnykh iadov i vysokoi vneshnei temperatury.

The experiments on Wistar rats have shown that administration of the hepatotropic poisons tetrachloromethane and polychlorpinene increased an immune response to T-dependent antigens. The combined exposure of the body to the hepatotropic poisons and high ambient temperatures leads to a drastically marked inhibition of immune responses to T-dependent and T-independent antigens. High ambient temperatures enhance a release of a comparatively high-molecular weight immuno-suppressor factor in tetrachloromethane-intoxicated rats, as well as induce production of a comparatively low-molecular weight immunosuppressor factor in the intoxicated rats who retain their splenocytic capacity of generating a low-molecular weight immunostimulating factor. The higher sensitivity retain their splenocytic capacity of generating a low-molecular weight immunostimulating factor. The higher sensitivity of splenocytes from rats with toxic hepatic lesion to elevated ambient temperatures is accounted for by their influence on humoral factors of intoxicated animals' sera.

Effects of 4-ipomeanol on bovine parainfluenza type 3 virus-induced pneumonia in calves.

Previous research has demonstrated that 4-ipomeanol toxicosis can enhance the severity of para-influenza virus-induced pneumonia in mice. The objectives of this study were to determine whether calves are susceptible to 4-ipomeanol-induced enhancement of parainfluenza type 3 viral pneumonia and to determine whether 4-ipomeanol alters pulmonary replication of parainfluenza virus. Male Holstein calves were injected with either 4-ipomeanol (3 mg/kg) or vehicle (polyethylene glycol) 3 days prior to intratracheal inoculation with either parainfluenza virus or sham inoculum of culture medium. Calves in the four treatment groups (ipomeanol-parainfluenza, ipomeanol-medium, vehicle-parainfluenza, and vehicle-medium) were necropsied at 5 days after inoculation with parainfluenza virus or medium. The lungs were studied by correlated methods of light and electron microscopy, digitizing morphometry and pulmonary lavage to quantitate the severity of pneumonia. Pulmonary viral titers were determined, and viral antigen was identified in the lung by immunoperoxidase technique. The calves in the ipomeanol-virus treatment group had over a 9-fold higher (P less than 0.05) volume density of virus-induced interstitial pneumonia than did the calves in the other three treatment groups. This 4-ipomeanol-enhanced viral pneumonia was associated with significantly greater (P less than 0.05) numbers of pulmonary macrophages and neutrophils in the lavage fluid and higher (P less than 0.05) pulmonary titers of pulmonary infectious parainfluenza virus. Four-ipomeanol-enhanced viral pneumonia was characterized in part by extensive hyperplasia of type II alveolar epithelial cells and by dense aggregates of macrophages and neutrophils in alveolar spaces and interalveolar septa. The results indicate that 4-ipomeanol exacerbates interstitial pneumonia in calves induced by bovine parainfluenza type 3 virus.