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PubMed1989

GABA innervation in adult rat oculomotor nucleus: a radioautographic and immunocytochemical study.

GABA innervation in the adult rat oculomotor nucleus (n.III) was investigated using two complementary approaches: radioautography after incubation of brain slices with tritiated GABA ([3H]GABA) along with local in vivo microinjections of the tracer, and GABA immunocytochemical procedures involving antibodies directed against a GABA-glutaraldehyde-protein conjugate. As determined by radioautography after in vitro or in vivo labelling, the [3H]GABA uptake sites in the n.III mainly involved axon terminals. These were distributed throughout the neuropil and were often closely apposed to unlabelled motoneuron somata. A small number of glial cells also showed preferential accumulation of the tracer. The GABA-immunostaining likewise involved axon terminals throughout the nucleus, but no glial cells were immunopositive. In the dorsal region of the structure, occasional GABA-immunostained internuclear neurons were observed among unstained motoneuron cell bodies. Electron microscopic examination of [3H]GABA-labelled or GABA-immunostained profiles in n.III revealed axon terminals of around 1 micron in diameter, always filled with small, round synaptic vesicles homogeneously distributed throughout the axoplasm. These boutons frequently contained mitochondria and one or more large granular vesicles. In single thin sections, 35% of [3H]GABA-labelled, and 19% of GABA-immunostained varicose profiles exhibited a synaptic differentiation, suggesting the existence of a predominantly if not entirely junctional innervation. These synapses mostly involved dendritic trunks or dendritic branches and were usually of the symmetrical type. A few, which were always symmetrical, were also observed on large somata of motoneurons. Some of the dendrites synaptically contacted by GABA-immunostained axon terminals were themselves GABA immunoreactive. These data substantiate the idea that GABA is involved in the control of motoneuron activity in n.III, and provide a structural basis for the inhibitory role of this transmitter in oculomotor function.

Animals↗

PubMedDate not supplied

Light microscopic radioautographic study of the localization of an anti-allergic agent, Tranilast, in rat mast cells.

In order to demonstrate the localization of an anti-allergic agent, Tranilast, in the mast cells, light microscopic radioautography was performed. The mast cells collected from rat peritoneal cavity were incubated for 0 to 60 min in a medium containing 3H-Tranilast. After the incubation, they were fixed, embedded and processed for light microscopic radioautography. The radioautographic silver grains were frequently localized around and over the cytoplasmic granules and their number increased according to the prolongation of incubation time. From the results obtained at present it was demonstrated that Tranilast was rapidly taken into the cytoplasm of mast cells. This phenomenon may suggest an important role of this agent in the inhibition of allergic reactions of mast cells.

Animals↗

PubMed1984

Assessment of resolution by half distance values for tritium and radioiodine in electron microscopic radioautographs using Ilford L4 emulsion developed by "solution physical" or D-19b methods.

Half distance values for electron microscopic (EM) radioautographs with the isotopes 3H and 125I were determined using Ilford L4 emulsion processed with either fine grain, solution physical development, or filamentous grain, chemical development with D-19b. 3H- and 125I-line sources, obtained by cutting perpendicular sections from sections of 3H-labeled methacrylate or 125I-labeled thyroid glands, were processed for EM radioautography. The distribution of silver grains around a line source was determined by measuring their distance from the source in photographs of EM radioautographs. The number of silver grains per unit distance from the line source was plotted on graphs and half distance values were calculated. With solution physical development, the half distance value was 74 nm for 3H and 80 nm for 125I; whereas with D-19 b development it was 187 nm for 3H and 157 nm for 125I. Since solution physical development produced a reduction of about 50% in the half distance values for both isotopes, it is concluded that the production of fine grain by this method provides better resolution for EM radioautography than filamentous grain development with D-19b.

Autoradiography↗

PubMed2005

Effects of the mGluR2/3 agonist LY354740 on computerized tasks of attention and working memory in marmoset monkeys.

RATIONALE: LY354740 is a recently developed metabotropic glutamatergic receptor 2 and 3 (mGluR2/3) agonist. A high density of mGluR2 has been reported in terminal fields of the perforant path in rodents and humans, suggesting its involvement in cognitive functions mediated by the temporal lobe, including memory. A small number of in vivo studies in rodents have assessed the effects of LY354740 on memory tasks, reporting the induction of impaired memory for spatial orientation in a water maze task and for delayed match and non-match to position in an operant version of these tasks. OBJECTIVE: In the present primate study, we used radioautography to describe the distribution and intensity of (3)H-LY354740 binding in the hippocampal formation of the common marmoset monkey (Callithrix jacchus) relative to the rat. In the major, in vivo part of the study, the effects of systemic LY354740 on computerized tasks of attention and memory were investigated. METHODS: Adult common marmosets were trained to perform a five-choice serial reaction time (5-CSRT) task and a concurrent delayed match-to-position (CDMP) task from the Cambridge Neuropsychological Automated test Battery (CANTAB). Filter tests of LY354740 effects on motor dexterity and motivation for reward revealed high inter-individual variation in sensitivity; therefore, on the 5-CSRT, subjects were tested at a dose range of 3--10 mg/kg, and on the CDMP, subjects were tested at 1--3 or 3--10 mg/kg. RESULTS: Radioautography revealed a relatively low level of (3)H-LY354740 binding in the marmoset hippocampal formation compared to the rat. Despite low binding, LY354740 reduced sustained-attention accuracy in the 5-CSRT, and reduced accuracy in two stages of the CDMP. CONCLUSIONS: The current study provides novel evidence for the importance of mGluR2/3 in the regulation of primate cognitive functioning.

Animals↗

PubMed1985

Terminal glycosylation in rat hepatic Golgi fractions: heterogeneous locations for sialic acid and galactose acceptors and their transferases.

Endogenous acceptors for N-acetylglucosamine (GlcNAc), galactose (Gal) or sialic acid (NeuAc) transfer were labeled to high activities when purified hepatic Golgi fractions were incubated with the corresponding radiolabeled nucleotide sugar in the absence of detergent. The in vitro conditions which were optimal for the endogenous glycosylation of GlcNAc and Gal acceptors (Mn2+, ATP) also promoted fusion within a subset of Golgi membranes. Electron microscope radioautography revealed that the majority of NeuAc acceptors were associated with unfused Golgi membranes, whereas the majority of Gal acceptors were localized to fused membranes. GlcNAc acceptors were approximately equally distributed between fused and unfused membranes. Under conditions in which Golgi membrane fusion was absent (-Mn2+), only NeuAc transfer was active. The majority of endogenous NeuAc acceptors were consequently assigned to the more trans regions of the hepatic Golgi apparatus as concluded from a combination of radioautography (NeuAc transfer) and acid NADPase cytochemistry (reactive medial and trans Golgi saccules). The distribution of NeuAc and Gal transferases was assessed after Percoll gradient centrifugation of disrupted Golgi fractions. The median density of NeuAc transferase was lower than that of Gal transferase. The studies are indicative of distinct Golgi components harboring the majority of acceptors and enzymes for terminal glycosylation.

Acetylglucosamine↗

PubMed1975

Evaluation of [3-H]proline for radioautographic tracing of axonal projections in the teleost visual system.

The efficacy of [3-H]proline radioautography for tracing retinal ganglion cell projections to the optic tectum of the jewel fish, Hemichromis bimaculatus, has been compared with that of degeneration techniques. There was good agreement between the various methods. Retinal projections to the optic tectum of two other teleosts, the oscar, Astronotus ocellatus, and the goldfish, Carrasius auratus, were examined radioautographically. In addition to conventional methods of analysis, radioautograms were scanned in a slit microdensitometer and by an automated isodensity scanning system. Results of studies with the protein synthesis inhibitor, cycloheximide, are compatible with the suggestion that axonally transported proteins labeled with [3-H]proline may release diffusible precursors that are reincorporated into protein in adjacent regions. The possible advantages and limitations of radioautography of [3-H]proline-labeled axonally transported protein in brief or extended studies are discussed in terms of the results obtained in the teleost visual system.

Animals↗

PubMed1980

Localization of alpha-bungarotoxin binding sites to the goldfish retinotectal projection.

The optic tectum of the goldfish Carassius auratus is a rich source of alpha-bungarotoxin (alpha-Btx) binding protein. In order to determine whether some fraction of these receptors is present at retinotectal synapses, we have compared the histological distribution of receptors revealed by the use of [125I]alpha-Btx radioautography to the distribution of optic nerve terminals revealed by the use of cobalt and horseradish peroxidase (HRP) techniques. The majority of alpha-Btx binding is concentrated in those tectal layers containing primary retinotectal synapses. The same layers contain high concentrations of acetylcholinesterase (AChE), revealed histochemically. Following enucleation of one eye, there is a loss of alpha-Btx binding in the contralateral tectum, observed both by radioautography and by a quantitative binding assay of alpha-Btx binding. Approximately 40% of the alpha-Btx binding sites are lost within two weeks following enucleation. By contrast, no significant change in AChE activity could be demonstrated up to 6 months following enucleation. These results are discussed in light of recent studies which show that the alpha-Btx binding protein and the nicotinic acetylcholine receptor are probably identical in goldfish tectum. We conclude that the 3 main classes of retinal ganglion cells projecting to the goldfish tectum are nicotinic cholinergic and that little or no postdenervation hypersensitivity due to receptor proliferation occurs in tectal neurons following denervation of the retinal input.

Acetylcholine↗

PubMed1987

The pathways mediating affective defense and quiet biting attack behavior from the midbrain central gray of the cat: an autoradiographic study.

The purpose of this study was to describe the pathways which mediate feline affective defense and quiet biting attack behavior elicited from the midbrain central gray. In these experiments, methods of [3H]leucine and 2-deoxy-[14C]glucose (2-DG) radioautography were utilized in concert with the technique of electrical and chemical brain stimulation. Affective defense behavior elicited from the midbrain central gray is characterized by marked vocalization such as hissing and growling, pupillary dilatation, urination and piloerection. In contrast, quiet biting attack elicited from the midbrain central gray lacks overt autonomic signs observed with affective defense response as well as the stalking component which is typically associated with stimulation of the lateral hypothalamus. Nevertheless, central gray-elicited attack resulted in a directed bite of the neck of an anesthetized rat in a manner similar to that observed from the hypothalamus. Affective defense was elicited from the dorsal half of the midbrain central gray, while quiet biting attack was obtained following stimulation of the ventral half of the midbrain central gray, thus indicating a functional differentiation of the central gray with respect to these two forms of aggression. In a separate series of experiments, affective defense or quiet biting attack response was identified by electrical stimulation through a cannula electrode situated in the midbrain central gray. The affective defense responses were subsequently elicited following microinjections of D,L-homocysteic acid through the same cannula electrode in order to demonstrate that these responses were the result of direct stimulation of cell bodies within the central gray. Then, one of the following autoradiographic tracing procedures was utilized: (1) [3H]leucine was injected through a cannula electrode and the animal was sacrificed after a 4- to 14-day survival period; or (2) a 2-DG solution was systemically injected and electrical stimulation was applied through the cannula electrode in order to metabolically activate the pathways associated with each of these responses. In general, the pattern of labelled target regions as indicated by 3H-amino acid radioautography was similar to that obtained from the 2-DG autoradiographic analysis. The principal ascending pathway associated with affective defense was traced to the anteromedial hypothalamus and medial thalamus. Concerning descending projections, label was traced into the central tegmental fields of the midbrain and pons, locus coeruleus and motor and main sensory nuclei of the trigeminal complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1984

Phosphorylation of non-histone proteins associated with mitosis in HeLa cells.

Our previous studies indicated that certain non-histone proteins (NHP) extractable with 0.2 M NaCl from mitotic HeLa cells induce germinal vesicle breakdown and chromosome condensation in Xenopus laevis oocytes. Since the maturation-promoting activity of the mitotic proteins is stabilized by phosphatase inhibitors, we decided to examine whether phosphorylation of NHP plays a role in the condensation of chromosomes during mitosis. HeLa cells, synchronized in S phase, were labeled with 32P at the end of S phase, and the cells subsequently collected while they were in G2, mitosis, or G1. Cytoplasmic, nuclear, or chromosomal proteins were extracted and separated by gel electrophoresis. The labeled protein bands were detected by radioautography. The results indicated an 8-10-fold increase in the phosphorylation of NHP from mid-G2 to mitosis, followed by a similar-size decrease as the cells divided and entered G1. The NHP phosphorylation rate increased progressively during G2 traverse and reached a peak in mitosis. Radioautography of the separated NHP revealed eight prominent, extensively phosphorylated protein bands with molecular masses ranging from 27.5 to 100 kD. These NHP were rapidly dephosphorylated during M-G1 transition. Phosphorylation-dephosphorylation of NHP appeared to be a dynamic process, with the equilibrium shifting to phosphorylation during G2-M and dephosphorylation during M-G1 transitions. These results suggest that besides histone H1 phosphorylation, phosphorylation of this subset of NHP may also play a part in mitosis.

Autoradiography↗

PubMed1984

Ocular localization of circulating bacterial lipopolysaccharide.

A bacterial lipopolysaccharide (LPS) extracted from a rough strain of Salmonella minnesota ( Re595 ) containing primarily lipid A was used to study tissue distribution following its intravenous injection in rabbits. For this purpose, the Re595 was either labelled with 125iodine (125I) and localization quantitated by gamma radiation spectrometry and radioautography of different tissues or a fluorescein labelled antibody to Re595 was employed. Localization of [125I]- Re595 or LPS was looked for at 30 min and 2 hr after intravenous injection. [131I]-albumin was employed either to measure intravascular protein or total tissue protein and, in some studies, [131I]-albumin and [125I]-fibrinogen were used to measure protein after unlabelled Re595 . Both fractions of isotopes injected and estimates of tissue-bound Re595 were made in the whole eye, liver, spleen, kidney and lung and in isolated iris-ciliary processes, aqueous, lens, vitreous, and posterior segment (retina, choroid, and sclera). Aqueous and iris-ciliary processes, but no other tissues, showed a marked extravazation of [131I]-albumin and [125I]-fibrinogen. [125I]- Re595 was found to localize primarily in liver and spleen. At 30 min, [125I]- Re595 was found in nanogram quantities within the eye and at 2 h greater amounts of LPS were found in iris-ciliary processes and aqueous than in the posterior segment. Neither radioautography nor fluorescein-labelled antibody to Re595 showed evidence of histologic localization of LPS in the iris-ciliary processes. These results indicate that although LPS does not localize preferentially in the eye, it does accumulate in quantities sufficient to have an effect locally.

Animals↗

PubMed1989

Induction of intestinal glucose carriers in streptozocin-treated chronically diabetic rats.

The maximal transport capacity (Vmax) for intestinal glucose absorption is increased in experimentally induced chronic diabetes mellitus. Using [3H]phlorizin radioautography, we examined the relation between this increase in transport Vmax and the number and distribution of sodium-glucose co-transporters on the luminal surface of rat ileum. Male Lewis rats were made diabetic with streptozocin. Ninety days later we measured 3-O-methyl-D-glucopyranose absorption and specific [3H]phlorizin binding to the ileal mucosa of the same rats. Net 3-O-methyl-D-glucopyranose flux was 6.9-fold greater in diabetic rats compared with age-matched controls. Specific binding of [3H]phlorizin to the luminal surface was 7.2-fold greater in the diabetic rats. Radioautography revealed that, in chronic diabetes, specific phlorizin binding extends into the midvillus region of the ileum, whereas in age-matched controls, it is confined to villus tips. We believe that, in untreated diabetes, a larger fraction of intestinal villus epithelial cells participate in glucose absorption.

3-O-Methylglucose↗

PubMed1987

Central GABAergic innervation of the pituitary in goldfish: a radioautographic and immunocytochemical study at the electron microscope level.

The GABAergic innervation of the goldfish pituitary was studied at the light and electron microscope levels by means of radioautography after in vitro incubation in tritiated gamma-aminobutyric acid (GABA) and immunocytochemistry using antibodies against GABA. Following incubation of pituitary fragments in a medium containing tritiated GABA, a selective uptake of the tracer was observed within the digitations of the neurohypophysis. Silver grain clusters were also observed in the adenohypophyseal tissue. At the electron microscope level, this uptake was found to correspond to nerve endings containing small clear and dense-core vesicles. These labeled profiles were located mainly in neurohypophyseal digitations in close apposition with the basement membrane separating the neurohypophysis from the adenohypophysis. However, they were also encountered in direct contact with most adenohypophyseal cell types in the different lobes. These results were confirmed by immunocytochemical data demonstrating the presence of numerous GABA immunoreactive fibers in both anterior and neurointermediate lobes. They were found either in the digitations of the neurohypophysis or in the adenohypophysis in direct contact with the glandular cells with a distribution and an ultrastructural aspect similar to those observed by radioautography. These data demonstrate that the pituitary of teleosts receives a massive GABAergic innervation. Although physiological data providing a functional significance for such an innervation are lacking, the present study suggests that, as already documented in mammals, GABA may be involved in the neuroendocrine regulation of pituitary functions in teleosts.

Animals↗

PubMedDate not supplied

In vivo thrombolysis. An experimental model in rhesus monkeys.

An experimental model of diffuse thromboembolism in the intrarenal circulation of the rhesus monkey was produced by intra-arterial injection of homogenised, homologous [125-I]fibrin. A sequential study of thromolysis was carried out using the conventional method of determining the thromboembolic index in the arteries of both kidneys together with radioautography and counting of radioactivity in the renal homogenate. Quantitative estimation of radioactivity in the renal homogenate, as well as radioautography of kidney sections provided more accurate and sensititve indices of the thrombolytic process than the conventional thrombembolic index. Studies on blood coagulation and fibrinolysis revealed only mild changes corresponding to the dynamics of thrombolysis in vivo. It was further noted that the thrombolytic mechanism in rhesus monkeys is very active and can clear thromboemboli from the intrarenal arteries within 8 days of their induction

Animals↗

PubMed1981

Failure to demonstrate morphologically the presence of colostral or milk cells in the wall of the gastrointestinal tract of the suckling neonatal mouse.

The possibility that intact cells may migrate from ingested colostrum and milk into the gut wall of the nursing neonate has been tested directly by means of radioautographic techniques. [3H]Thymidine was continuously infused into female mice throughout the last 6 days of their pregnancy. Upon delivery, their fully [3H]thymidine-labelled litters were removed and given to nurse from unlabelled surrogate mothers whose own litters were borne simultaneously. These unlabelled litters were similarly removed immediately upon birth and given to the [3H]thymidine-infused mothers to nurse. Infants labelled during gestation and mothers labelled during pregnancy continued to receive thrice-daily injections of isotope for 1-14 days and 1-18 h, respectively, after delivery. The stomach and adjacent portion of small intestine were removed from unlabelled infants nursing from labelled surrogate mothers at intervals of 1-18 h after beginning to suckle, subserially sectioned and prepared for radioautography. From days 1 to 14 after beginning to suckle, the same tissues were removed from labelled infants nursing from unlabelled surrogate mothers and similarly prepared for radioautography. The results indicate that transepithelial migration of intact cells of the colostrum and milk does not appear to be the method by which immunological functions are adoptively transferred to the nursing neonatal mouse.

Animals↗

PubMedDate not supplied

Inability of chrysotile asbestos fibers to modulate the 2-acetylaminofluorene-induced UDS in primary cultures of rat hepatocytes.

There is now growing evidence that asbestos fibers could act in association with genotoxic compounds, either as cocarcinogens or promoters, in the process of carcinogenesis. The hepatocyte/UDS assay system has been taken to advantage to investigate the capacity of fibers to modulate the effects of genotoxic compounds on the cell, as we previously demonstrated the hepatocytes can engage in phagocytosis of chrysotile fibers. Measurement of UDS was performed by a biochemical procedure involving liquid scintillation counting (LSC) of a purified DNA fraction as well as by radioautography. Both LSC and radioautography revealed that chrysotile asbestos fibers UICC B at concentrations up to 100 micrograms/ml do not elicit UDS, whereas 2-acetylaminofluorene (2-AAF) at low concentrations (0.05-0.625 micrograms/ml) significantly induces it in parallel positive controls. In an attempt to test the cocarcinogen hypothesis, cultures of hepatocytes were simultaneously exposed for 20 h to 2-AAF (0.05 and 0.25 micrograms/ml) and asbestos fibers (1 and 10 micrograms/ml) given as simple mixtures. It was found that the 2-AAF-induced UDS activity was the same whether fibers were present or not. This was observed with both UDS evaluation procedures at all concentration combinations selected. An analysis of variance applied to the data collected from several experiments confirmed that there was no significant 2-AAF-fiber interaction. Our data suggest the absence of intrinsic genotoxic properties for chrysotile fibers. They also indicate that the modulation of the cellular response to genotoxic agents by asbestos fibers is not detected under our test conditions and may require longer-term exposures to be expressed.

2-Acetylaminofluorene↗

PubMed1983

Developmental and neurochemical specificity of neuronal deficits produced by electrical impulse blockade in dissociated spinal cord cultures.

Blockade of spontaneous electrical activity in dissociated fetal spinal cord cultures produced neuronal deficits as measured by biochemical and morphological techniques. Spinal cord cultures exhibited an age-dependent vulnerability to impulse blockade with tetrodotoxin (TTX) or xylocaine. Neuronal cell counts, [125I]tetanus toxin fixation and [125I]scorpion toxin binding indicated that TTX application produced neuronal deficits during the second or third week in culture. Application of TTX during the first or fourth week did not produce a difference in tetanus toxin fixation from controls. Radioautography of [125I]tetanus toxin revealed no obvious change in the label distribution after TTX treatment. Suppression of electrical activity during the first 6 days in culture had no effect on choline acetyltransferase (CAT) activity and no apparent effect on the appearance of the cultures. Application of TTX during the seventh day in culture decreased CAT activity to 68% of control. Chronic electrical blockade produced a progressively greater loss of CAT activity through 21 days in culture. GABAergic neurons, as indicated by high-affinity GABA uptake, glutamic acid decarboxylase activity and [3H]GABA radioautography, were not affected by electrical blockade. These data indicate that there is developmental and neurochemical specificity in the neuronal death produced by blocking spontaneous electrical activity in dissociated spinal cord cultures.

Animals↗

PubMed1982

Identification of the protein cross-linked to 3'-terminus of 5 S RNA in rat liver ribosomal 60 S subunits.

To cross-link the 3'-terminus of 5 S RNA to its neighbouring proteins, ribosomal 60 S subunits of rat liver were oxidized with sodium periodate and reduced with sodium borohydride. 5 S RNP was then isolated by EDTA treatment followed by sucrose density-gradient centrifugation and subjected to SDS-polyacrylamide gel electrophoresis. The protein with a slower mobility than the L5 protein, which was thought to be cross-linked 5 S RNP, was labeled with 125I, treated with RNAase, and analyzed by two-dimensional polyacrylamide gel electrophoresis, followed by radioautography. A radioactive spot located anodically from L5 protein was observed, suggesting that it is the L5 protein-oligonucleotide complex. When analyzed by SDS slab polyacrylamide gel electrophoresis followed by radioautography, the peptide pattern of the alpha-chymotrypsin digest of this 125I-labeled protein-oligonucleotide complex was similar to that of the digest of 125I-labeled L5 protein. The results indicate that L5 protein binds to the 3'-terminal region of 5 S RNA in rat liver 60 S subunits.

Animals↗

PubMed1988

A carcinogenesis reversibility study of the effects of butylated hydroxyanisole on the forestomach and urinary bladder in male Fischer 344 rats.

A reversibility study was initiated to determine if the length of feeding with 2% butylated hydroxyanisole (BHA) altered the incidence of forestomach lesions observed after a 24-month observation period. Groups of male Fischer 344 rats were fed 2% BHA for 0, 3, 6, 12, and 24 months and then the basal diet for the completion of the 24-month experimental period. Subgroups were serially sacrificed for histopathological examination and [methyl-3H]thymidine radioautography at the time when each group of animals was transferred to the basal diet and also at 15 months. The results showed that except for carcinomas and some epithelial downgrowths, cellular proliferation, measured by radioautography in the epithelium lining the greater and the lesser curvature of the forestomach, remained dependent on the continuous presence of 2% BHA for, at least, 12 months. Superficial hyperplasias, inflammatory lesions and many of the papillomas regressed after cessation of treatment at 12 months. The epithelial downgrowths did not appear to enlarge after the BHA was withdrawn. The squamous cell carcinomas occurred in almost identical yields whether the rats were fed 2% BHA for 12 months and then returned to the basal diet for 12 months or received 2% BHA continuously for 24 months. It is shown here that at several times, 2% BHA stimulated the [methyl-3H]thymidine labelling index of the transitional epithelium of the urinary bladder and that at 3 months the no observed effect level was greater than 0.5% BHA. The significance of the studies on the forestomach and bladder epithelia are discussed. It is concluded that the lesions induced by BHA are most unlikely to be relevant to humans exposed to much lower levels of BHA.

Administration, Oral↗