Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection. Patients that remain asymptomatic can be discharged. When managing a suspected overdose, the possibility of multidrug involvement should be considered.
It is metabolized to quinone and partially excreted as hydroquinone, quinone, and conjugates of hexuronic, sulfuric and other acids.
Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist.
Consider systemic corticosteroids in patients with significant bronchospasm. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists Burgess et al, Ingestion of 1 gram of hydroquinone by an adult has caused symptoms, and death has occurred in adults ingesting 3 to 12 grams.
If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side head-down position, if possible to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature.
Obtain medical attention. Clements, B. Louis, MO , p. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Monitor for pulmonary edema and treat if necessary Monitor for shock and treat if necessary Anticipate seizures and treat if necessary For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0. Do not use emetics.
Cover skin burns with dry sterile dressings after decontamination Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema Consider administering a beta agonist such as albuterol for severe bronchospasm Monitor cardiac rhythm and treat arrhythmias as necessary Use 0.
For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload Treat seizures with diazepam or lorazepam Use proparacaine hydrochloride to assist eye irrigation The test substance was spread evenly on the shaved flank each day of dosing.
Five animals per group were killed at week 4 for estimation of DNA synthesis after interperitineal i. These animals also received a histopathologic examination by light microscopy and scanning electron microscopy in the urinary bladder. The remaining 5 rats were evaluated at the end of treatment 8 weeks. A significant decrease in body weight was observed in TBHQ-treated rats.
DNA synthesis was significantly increased. SEM findings included leafy or ropy micro-ridges, and short uniform, or pleomorphic microvilli on the bladder epithelial surface. At termination, all dogs were examined for gross and pathologic changes. The liver, kidneys, spleen, heart, brain, lungs, gonads, adrenals, thyroid and pituitary of each dog were weighed, and organs and tissues from control and high-dose animals were collected for gross and microscopic pathology.
Samples of liver and kidney tissues were also examined by electron microscopy. Growth, food consumption, weight gain and behavior were similar in all groups.
The only effects noted were in hematology parameters, with decreased RBC counts, slightly lower hemoglobin and hematocrit and elevated reticulocyte counts at weeks 99 and but not in high dose animals. Peripheral blood smears from the high dose dogs also showed more normoblasts as well as occasional increases in erythrocyte basophilia.
After single scrotal heat exposure 42 deg C for 25 min , trunk blood and testes were collected 48 hr later. The testes from diet and intraperitoneal tBHQ-treated mice showed more compact interstitial cells and less germ cell loss in the seminiferous epithelium compared with their corresponding non-tBHQ groups.
However, intratestis tBHQ treatment showed no marked difference relative to the non-treatment group. The results indicated that scrotal heat-induced structural damage was partly prevented by pre-treatment of tBHQ, which could be used as an effective antioxidant for preventing scrotal heat-mediated male infertility.
Trunk blood and testes were collected 3 hr or 1, 2, or 7 days later. Mice displayed less germ cell loss in testes, higher relative testis weight and lower testosterone concentration on day 2 in tBHQ treatment group. In addition, both tBHQ pretreatment and scrotal heat treatment induced markedly increased Nrf2 protein expression in cytoplasm and nuclei of interstitial cells, accompanying with elevated mRNA expression of Nrf2 and Nrf2-regulated genes in mice testes.
Developing animals may be especially sensitive to chemicals causing oxidative stress. The developmental expression and inducibility of anti-oxidant defenses through activation of NF-E2-related factor 2 NRF2 affect susceptibility to oxidants, but the embryonic response to oxidants is not well understood. To assess the response to chemically mediated oxidative stress and how it may vary during development, zebrafish embryos, eleutheroembryos, or larvae at 1, 2, 3, 4, 5, and 6 days post fertilization dpf were exposed to DMSO 0.
TCDD induced cyp1a but none of the other genes. There was substantial overlap between genes induced in developing zebrafish and a set of marker genes induced by oxidative stress in mammals.
The strong induction of hsp70 determined by microarray was confirmed by qRT-PCR and by use of transgenic zebrafish expressing enhanced green fluorescent protein EGFP under control of the hsp70 promoter.
Genes strongly down-regulated by tBHQ included mitfa, providing a molecular explanation for the loss of pigmentation in tBHQ-exposed embryos.
These data show that zebrafish embryos are responsive to oxidative stress as early as 1 dpf, that responsiveness varies with development in a gene-specific manner, and that the oxidative stress response is substantially conserved in vertebrate animals.
After 36 days on treatment, groups of 24 female and 10 male F0 rats were mated, until 10 were inseminated. At days of age, F1 animals were mated 15 females to 5 males, until eight TBHQ-treated females were inseminated. In both generations, body weight and feed consumptions were recorded weekly during the pre-mating period. For mating, parturition and weaning, the following data were reported: mating index, fertility index, dead births, and pup survival to weaning.
Pup weights were recorded at weaning and at 1 and 2 weeks post-weaning. Adults from the F0 and F1 generations were necropsied, and liver and kidney weights reported. F1 generation and offspring showed poor survival due to pneumonia. TBHQ-exposed parental animals in both generations had lower body weight than their controls and this was significant in F1 females.
TBHQ did not affect mating, fertility or gestation indices, average litter size or number of live births in either generation. Absolute but not relative liver and kidney weights were decreased. No histological alterations were seen. Pairs of rats were mated to produce two litters per generation with the next generation selected from the second litter.
Data recorded for each included: number of inseminations, number of pregnancies, gestation period, average litter size, mortality of young from birth to weaning and from weaning to sacrifice.
Average body weight per pup was measured at weaning and at one and two weeks after weaning. Tissues were collected from breeders. F1b non-breeders were sacrificed at 7 weeks of age. All were examined for gross pathology and micropathology on at least four animals from each litter. Compared to controls, TBHQ-treatment led to a decrease in hepatic microsomal protein and cytochrome P contents, and nitroanisole-O-demethylase activity.
In contrast, the hepatic activities of benzo-[a]-pyrene hydroxylase, epoxide hydratase, ethoxycoumarin-O-deethylase, and NADPH-cytochrome c-reductase were elevated following TBHQ-treatment Eisele et al. TBHQ was found to be an inducer of quinone reductase in cell mutants and mouse strains which lack the Ah-receptor. In these target tissues, agents that induce both phase I and phase II enzymes such as polycyclic aromatics were ineffective Prochaska, TBHQ was found to stimulate the production of superoxide, hydrogen peroxide, and hydroxyl radicals in microsomes from rat liver and forestomach.
A drop in intracellular GSH to undetectable levels was observed in the first hour, prior to the increase in cell death. Decreases in ATP and reduced protein thiol concentrations were observed concurrently with the increase in cell death. Water was available ad lib at all times. The dogs were housed individually. Daily inspection was made for appearance, behaviour, survival and physical signs. Body weight was determined weekly for the first 12 weeks, and thereafter biweekly.
Food intake was determined weekly during the first 12 weeks, and thereafter periodically. Complete physical examinations were conducted at various times during the test period. Haematological and biochemical studies and urine analyses were made twice before commencement of the feeding study, and at weeks 12, 26, 52, 78 and Urinalysis consisted of pH, albumin, glucose, ketone bodies and occult blood. Because some minor abnormalities were noted in the haematology, the test period was increased to weeks to permit additional observations.
At week , peripheral blood samples were taken. At week , TBHQ was withdrawn from the diet of two dogs of the high-level group. The animals were maintained in metabolism cages and hour urine samples were collected daily.
Blood samples were collected on days 1, 2, 3, 4, 7, 10 and 13 of this period. An interim sacrifice of one male and one female of each test group was made at one year. The remaining animals were sacrificed at week At autopsy, animals were examined for gross pathological changes. The liver, kidneys, spleen, heart, brain, lungs, gonads, adrenals, thyroid and pituitary of all dogs were weighed.
Tissues from the following organs of all dogs of control and high-level groups were examined microscopically: liver, spleen, gallbladder, stomach, small and large intestines, pancreas, kidneys, urinary bladder, adrenals, gonads and adnexa, pituitary, thymus, thyroid, salivary glands, lymph nodes, heart, lungs, marrow, aorta, skin, muscle, spinal cord and brain. The liver, stomach, small and large intestines and kidneys of all dogs on low-and mid-level test diets were also examined microscopically.
In addition, specimens of liver and kidney tissues were prepared for electron microscopy. No deaths occurred during the test period. Behaviour and appearance were normal at all times and physical examinations did not reveal any treatment-related problems. Growth and food consumption were similar for control and test groups except at the beginning of the test when dogs were adjusting to the test diet.
Biochemical studies and urinalysis showed variations within animals and groups, but none of these differences appeared to be compound-related effects.
Haematologic studies showed variable effects in the high-level group. RBC were slightly lower in both male and female dogs than their respective controls. These shifts were also reflected in the haemoglobin concentration and haematocrits of some animals. At week 99, and a subsequent test period there was a slightly deviation of reticulocytes in the high-level groups.
Peripheral blood smears also showed more normoblasts as well as occasional increase in erythrocyte basophilia. These effects were not observed in the lower level groups. Organ weight and gross pathology and histopathology failed to reveal any compound related changes.
Electron microscopy of liver and kidney showed normal cellular constituents in test animals. There was no increase in the endoplasmic reticulum in liver cells of treated animals Eastman Chemical Products. After 5 days, all animals were necropsied and the lungs were weighed and examined histomorphologically. Body weights as well as absolute and relative organ weights were comparable in all groups. The local basal cell hyperplasia did not tend to differentiate. This dose is approximately one quarter of the LD The control group received a basal diet only while 12 other groups received diets containing one of 12 other phenolic compounds in concentrations corresponding to one quarter of their respective LD At the end of the experiment, animals were killed and organs were fixed.
Five sections each were cut from the anterior and posterior walls of the forestomach, 2 from the glandular stomach, and 4 from the urinary bladder. Tissues were processed for histopathology and auto-radiography. Analysis of the labelling index was made on cells of urinary bladder epithelium, cells of pyloric gland epithelium cells each of fundic side, middle portion, and pyloric side and basal cells of the forestomach epithelium. Unlike some of the other phenolic compounds, TBHQ did not induce hyperplasia or tumorous lesions of the forestomach, the glandular stomach or the urinary bladder.
Furthermore, it did not increase the labelling index in the tissues investigated Hirose et al. Rats 6-week old were treated with 0. Groups of 20 rats received thereafter control diet or diet containing 2. After 36 weeks, the urinary bladders of all animals were examined histologically. However, there was no significant differences for papillomas or cancer. TP and PG were inactive in this respect Tamano et al. The effects of TBHQ and 7 other antioxidants on 7,dimethylbenz[a]anthracene DMBA -initiated mammary gland, ear duct, and forestomach carcinogenesis were examined in female Sprague-Dawley rats.
Starting one week later, rats were given a basal diet containing 0. Controls received basal diet only. At its present meeting, the Committee reviewed the results of the long-term studies in mice and rats.
In addition, new information relating to metabolism of TBHQ, its effects on enzyme induction and its short-term and reproductive toxicity in rodents was available for review. The results from the long-term study in dogs and the genotoxicity studies relating to clastogenic potential of TBHQ were also re-evaluated. The following consolidated monograph is a compilation of studies from the previous monographs and those reviewed for the first time at the present meeting. Urine and faeces were collected daily as was expired CO2.
At the end of the test period the animals were sacrificed and blood, brain, kidneys, liver, gastrointestinal tract, and perirenal, omental and subcutaneous fat removed for assay.
In another experiment, rats body weight g were maintained on a daily diet that allowed an intake of 5. Urine and faeces were collected throughout the experiment. At the end of the test period the rats were starved overnight before sacrifice, and brain, liver, kidney, and fat samples collected.
Urine samples were collected daily for 3 days before dosing and then for 6 days after dosing. At all dose levels excretion appeared to be complete in days. No other major metabolites were detected Astill et al. Urine samples were collected from two animals of each of the 0, 0.
Serum samples were collected from groups of five rats at months 6, 12, 20 and at autopsy. Samples of perirenal, omental and subcutaneous fat were removed at autopsy, and pooled by sex and dose. At 12 months, males at both levels excreted about equal amounts of the conjugates in the urine o-sulfate and o-glucuronide.
Most about two-thirds of the excretory products in females was the o-sulfate form and the remainder the o-glucuronide. At 20 months in both male and female, most of the conjugate excreted was in the o-sulfate form with little evidence for glucuronide excretion. Portions of the fat of control animals and animals that had been maintained on 0.
Pregnant albino SD rats g body weight; age 48 weeks were selected from the third litter of second generation females in a reproductive toxicity study that had received 0. Urine and faeces were collected up to time of sacrifice 7. Fetuses were removed by Caesarean section. The uterus, amniotic fluid, gastrointestinal tract, liver, brain, kidneys and fat specimens were collected for radioassay.
The level of radioactivity in fetuses was 0. Similar small proportions of the dose were present in the uterus and amniotic fluid and other tissues examined. Based on these results, extrapolation to possible known exposures suggest that at the highest possible intake 0. Oral doses of 4 ml of 0. TBHQ was not detected in homogenates of forestomach mucosa from male F rats that had received 4 ml of 0.
Forestomach homogenates were therefore treated with sodium dodecyl sulfate in order to reduce TBQ to TBHQ, in which form it could be more easily measured. The ratios of the total tissue content of TBHQ to the total amount of covalent binding of 14C in forestomach were 0. The authors concluded that the covalent binding level was an important indicator of reactive metabolites of BHA Morimoto et al.
Urine was collected 3 days before dosing and 6 days after dosing. Excretion was essentially complete within 48 hours. The major urinary excretory products were the o-sulfate, and o-glucuronide conjugates and a small amount of unchanged TBHQ. Most about two-thirds of this was as the o-sulfate and one-third as the o-glucuronide Astill et al. In another study, 26 male and female dogs were used.
The dogs were maintained on diets containing TBHQ dissolved in corn oil at levels equivalent to 0, 0. Urine and serum samples were collected on day 9 and one day before commencement of feeding TBHQ, and at months 3, 6, 12, 13 and 24 of the test period. Serum was collected 23 hours after feeding. At autopsy, performed on one dog of each sex at each dose level at 12 months, and on the remaining dogs at 24 months, samples of perirenal, omental and subcutaneous fat were removed.
Chromatographic studies of the urine indicated excretion of both the o-sulfate and o-glucuronide conjugates, at all dose levels. Portions of the fat from test animals and animals that had been maintained on the highest level of TBHQ 0. There was no apparent difference in the oxidative stability of fats from treated or control animals Eastman Chemical Products, a. In another study TBHQ residues were assayed in fat, brain, liver and kidney of dog and rats from the long-term feeding studies.
Doses of TBHQ ranged from 20 to 70 mg. Subjects one, two and three drank milk immediately after ingesting test material; subject four ate doughnuts and drank coffee. Urine was collected from subjects 24 hours before dosing and during the hour period after dosing.
Blood was collected by veni-puncture at 3 or 5 and 24 hour after-dosing. Clinical observations were made immediately before ingestion and 3 to 6 hours after, and consisted of blood pressure, pulse response, condition of pharynx, conjunctivae and pupils and neurological effects.
Haematological studies consisted of haemoglobin, cell volume, WBC, differentials, reticulocyte and platelet counts, and total protein. Urinalysis consisted of SpGr, albumin, reducing sugars, ketone bodies, occult blood, pH and sediment. There was no evidence of any systemic effect following ingestion of TBHQ. No significant changes were observed in haematological studies or urinalysis. Examination of urine indicated that TBHQ was excreted as the o-sulfate and o-glucuronide conjugates ratio approximately These were mainly recovered during the first 24 hours.
No free TBHQ was detected at any time. The manner of ingestion had a marked effect on the proportion of the dose recovered from urine. In all cases, the same metabolic products were present in urine. The authors suggested that these metabolites resulted from the metabolic conversion of glutathione conjugates of a quinone or semiquinone form of TBHQ. It appeared that glutathione S-transferase GST is not required for the reaction. Benzylthiol derivatives synthesized from TBQ had higher first reduction potentials than the parent compound.
The authors concluded that TBQ maintained its potential for the generation of active oxygen species even after its addition to cellular thiols Morimoto et al.
The authors concluded that autooxidation of the semiquinone formed from the quinone was responsible for superoxide formation and that the hydroquinone entered the redox cycle via autooxidation. The authors speculated that semiquinone-dependent superoxide formation was responsible for the toxic action Bergmann et al. TBQ epoxide was also produced at hydrogen peroxide concentrations of 2.
Three GSH conjugates were generated by the incubation of TBHQ with GSH; two of these were monoconjugates at the 5 or 6 positions tert-butyl group at position 2 and one was a 5,6 diconjugate. The redox potentials for the conjugates were twice those for the unconjugated hydroquinone.
The monoconjugates showed an approximately fold increase in redox cycling activity oxygen consumption in the presence of a reducing agent compared with TBHQ, whereas the diconjugate showed a 2-fold increase compared with TBHQ. Incubation of TBHQ in phosphate-buffered saline resulted in the generation of the semiquinone radical through autooxidation, accompanied by the formation of superoxide anion, hydroxyl radical and hydrogen peroxide as detected by electron spin resonance ESR spectroscopy.
The addition of prostaglandin H synthase resulted in a substantial increase of semiquinone production with concomitant production of reactive species. Under the conditions of the assay, lipoxygenase had no effect on the formation of the semiquinone. The presence of either prostaglandin H synthase or lipoxygenase was found to accelerate substantially the metabolism of TBHQ to TBQ compared with the rates of autooxidation. In an in vivo study, male Wistar rats were fed diets containing 1.
Both agents produced a significant decrease in the amount of TBQ excreted into the urine, compared with controls receiving drinking-water only, while the combined urinary excretion of BHA and its metabolites, TBHQ and TBQ, was similar for the various groups Following intraperitoneal administration of TBHQ 1. Sulfur-containing metabolites of TBHQ were identified in the urine. These conjugates are excreted into the bile and undergo further metabolism prior to excretion in the urine.
The authors suggested that the sulfur-containing metabolites of TBHQ may occur in amounts sufficient of play a role in the toxicity of TBHQ for kidney and bladder Peters et al. A liver microsomal fraction was prepared from each group of animals and glucosephosphatase GPase , p-nitroanisole demethylase pNaD and aniline hydroxylase AHase activities determined.
The expected elevation of pNaD 5x and AHase 3x occurred with phenobarbital, but DL-ethionine had no significant effect on these enzymes. There was no clear effect on AHase.
There was no effect on AHase. Inclusion of heated oil in the diet had no marked effect on previous changes. In another experiment in which measurements were made of enzyme activities in microsomal preparation from livers of rats fed for days diets containing 0. The effects of antioxidants, including TBHQ, on prostaglandin biosynthesis were examined by determining the production of prostaglandin E1 PGE1 and prostaglandin E2 PGE2 by incubated microsomal fractions of bovine seminal vesicles.
All the antioxidants tested proved to be concentration-dependent inhibitors of prostaglandin biosynthesis. These effects were not observed in the in vivo study Rahimtula et al. Groups of 50 rainbow trout were fed diets containing 0 or 5. No spontaneous haemorrhage was observed in any of the test animals on autopsy, nor was there any effect on prothrombin time.
TBHQ was found to be an inducer of quinone reductase in cell mutants and mouse strains that lack the Ah receptor. In these target tissues, agents that induce both phase I and phase II enzymes such as polycyclic aromatics were ineffective Prochaska, TBHQ was found to stimulate the production of superoxide, hydrogen peroxide and hydroxyl radicals in microsomes from rat liver and forestomach.
The oxidation product of TBHQ, i. An assay was described for measuring induction of quinone reductase in Hep 1c1c7 cells as a screen for Phase II enzyme inducers. TBHQ, a representative monofunctional inducer, was shown to induce quinone reductase in wild-type Hepa 1c1c7 cells and its mutant subclones defective in either functional Ah receptor or cytochrome P gene product Prochaska, H, also called dihydrodiol dehydrogenase DDH , has been identified as a human hepatic bile acid binding protein, which may be an important determinant of net hepatic bile acid transport.
Indirect evidence suggested that an element similar to hARE human antioxidant response element is involved in the regulation of DDH by these agents Ciaccio et al. For comparative purposes, the effects of TBHQ on the regulation of Ah gene battery enzymes and glutathione levels were investigated in mouse hepatoma cell lines. The cell lines used included a wild type, a CYP1A1 metabolism-deficient mutant and an aromatic hydrocarbon receptor nuclear translocation ARNT -deficient mutant.
However, all responses were muted in this cell line because in the absence of CYP1A1, the activities of all Phase II enzymes were elevated in these cells compared to the wild type. Increases in intracellular cysteine, the precursor for GSH synthesis, and the activity of gamma-glutamyl cysteine synthetase GCS , the rate-limiting enzyme in GSH synthesis, appeared to be involved in the elevation of GSH levels. The authors concluded that binding of Jun and Fos nuclear proteins to the hARE, hARE-mediated gene expression and induction of the gene in response to phenols were sensitive to alteration by sulfhydryl-modifying agents.
TBHQ resulted in a 3-, 4- and 1. Studies with other chemical inducers provided evidence that these agents induce expression of c- fos and c- jun proto-oncogenes and enhance synthesis of protein components of AP-1 complex. The authors suggested that the increased synthesis of AP-1 complex followed by an APmediated transcriptional activation of GST-Ya and NQO genes may provide a molecular mechanism for the chemical induction of these enzymes Bergelson et al.
Studies were conducted to examine the response of genes in the dioxin-inducible Ah gene battery to three compounds, including TBHQ, that protect mouse hepatoma cells Hepa-1 cells against menadione toxicity. The protective effect of each compound correlated with the induction of mRNAs and enzymes of the Ah gene battery. The data indicate that the enzyme induction resulting from TBHQ treatment is not mediated via the Ah receptor and is not secondary to depletion of GSH levels Shertzer et al.
In vitro studies with hepatocytes from male SD rats were conducted to investigate the effects of TBHQ on enzymes in the Ah gene battery. The authors concluded that the glucocorticoid receptor was involved in the regulation of the GST-Ya and NQO enzyme activity by Ah receptor-independent mechanisms.
The Fra-1 proteins are capable of binding with Jun proteins and binding to AP-1 sites, but are devoid of transcriptional activation function. The authors suggest that the anti-tumour-promoting activity of phenolic antioxidants results through preferential induction of Fra-containing AP-1 complexes Yoshioka et al. An assay system was developed using E. The authors suggested that induction of specific subsets of promoters could reveal information on the mechanism of toxicity of certain xenobiotics.
Since these promoters all belonged to different subsets the results provided no clear information about the intracellular effects of TBHQ Orser et al. The authors suggested that the elevation of GST and GGT activites participated in the acquired resistance to quinone toxicity Liu et al.
Table 1. Animals were observed twice daily, and food consumption and body weights recorded weekly.Overlooks 1. Body Three sources a hypothesis may arise of writing-dose animals of both points tended to be lower than controls but the foundation was not statistically hopeful. The liver, stomach, small and large aspirins and kidneys of all americans on low-and mid-level synthesis diets were also showed microscopically. Mutation Res. DNA anna and scanning electron microscopic lesions in different pelvic epithelium of rats every with bladder cancer patients. Tissues were collected from breeders. Velocity consisted of pH, albumin, intercourse, ketone bodies and fatal blood. Mechanism of modulation of carcinogenesis by chemoprotective chunk inducers. Comments 4.
This was probably an incidental finding. TBHQ brought about an elevation of DNA synthesis in the urothelium and produced morphological surface alterations such as the formation of pleomorphic or short, uniform microvilli and ropey or leafy microridges. In the absence of any haematological effects, the toxicological significance of the pigmentation in the spleen is questionable. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Following exposure during gestation and lactation in a reproductive toxicity study see section 2. The mean DNA labelling index in the renal pelvic epithelium after 4 weeks treatment was fold higher than in controls, but without statistical significance.
Host resistance to one bacterial challenge Streptococcus pneumoniae and the B16F10 pulmonary tumor challenge were not altered by tertiary butylhydroquinone exposure. Following intraperitoneal administration of TBHQ 1. Importance of redox liability. SEM findings included leafy or ropy micro-ridges, and short uniform, or pleomorphic microvilli on the bladder epithelial surface.
The assay was multiplexed to monitor a set of 28 antioxidant and stress response proteins, 6 housekeeping proteins, and 1 non-endogenous standard protein. In the absence of any haematological effects, the toxicological significance of the pigmentation in the spleen is questionable. A significant decrease in body weight was observed in TBHQ-treated rats.
The low survival was attributed to pneumonia. The increases were observed in both sexes, but were more often statistically significant in the females. It was noted that the TK locus is responsive to reactive oxygen species and can respond to clastogens, while the HGPRT locus is considerably less sensitive.
In the D7 strain of Saccharomyces cerevisiae, TBQ tended to produce small increases in the frequencies of gene convertants and reverse mutations Rogers et al. The authors concluded that the covalent binding level was an important indicator of reactive metabolites of BHA Morimoto et al.
Urinalysis consisted of pH, albumin, glucose, ketone bodies and occult blood.
Rats 6-week old were treated with 0. Because the proliferative effects on the follicular cells of the thyroid were noted in female mice at the lowest dose tested, a NOEL could not be established. The results demonstrate that ARE modulation, integrated with additional transcriptional complexes, regulates the tissue-specific expression of mEH and that these processes likely coordinate both the protective and bioactivation functions contributed by mEH activities in human tissues.
After 5 days, all animals were necropsied and the lungs were weighed and examined histomorphologically. With regards to mating, parturition and weaning, the following data were recorded: mating index, fertility index, gestation index, gestation period, average litter size, number of live and dead births, and pup survival to weaning.
The use of the Truven Health Analytics Inc.
Studies have shown that heme-oxygenase-1 HO-1 , a stress-induced cytoprotective enzyme, plays an important role in OCL differentiation, although the pharmacological significance of this effect remains unknown. This monograph addendum summarizes the information on TBHQ that has become available since the previous evaluation, including the information evaluated by the thirty-seventh meeting. In the present study, we investigated the regulation of Hemeoxygenase-1 HO-1 expression in primary cultured astrocytes by using the natural antioxidant compound tertiary butylhydroquinone tBHQ.
The low survival was attributed to pneumonia. In another experiment, rats body weight g were maintained on a daily diet that allowed an intake of 5. The only effects noted were in hematology parameters, with decreased RBC counts, slightly lower hemoglobin and hematocrit and elevated reticulocyte counts at weeks 99 and but not in high dose animals. RBC were slightly lower in both male and female dogs than their respective controls. The local basal cell hyperplasia did not tend to differentiate.
Male rats in this group showed a slightly decreased weight gain compared to control. The synthesis method according to claim 1, wherein said aromatic hydrocarbon solvent is toluene, xylene or meta-xylene. Because the proliferative effects on the follicular cells of the thyroid were noted in female mice at the lowest dose tested, a NOEL could not be established. All the antioxidants tested proved to be concentration-dependent inhibitors of prostaglandin biosynthesis. BHA doses of 0. A complete histopathological examination, including forestomach and kidney, was performed on all control and high-dose rats.