Potential Toxicity of Boric Acid Powder Otic Insufflation.

OBJECTIVE: Boric acid (BA) powder is commonly used to treat otologic conditions, such as mastoid bowl inflammation and chronic otitis externa. Exposure to 50 mg per day is thought to cause systemic toxicity in humans. Inflamed skin and mucosal surfaces readily absorb BA. The aim of this study was to measure the doses of BA commonly used in clinical otology and alert the otolaryngology community to BA's underappreciated potential source of systemic toxicity. STUDY DESIGN: Prospective, controlled. SETTING: Laboratory. METHODS: BA dose administration was measured by weighing the BA generated by common insufflators: accordion bellows, House-Sheehy insufflator, DeVilbiss insufflator, and pneumatic powder blower. Manual insufflation was performed with 3 compressions of the bulb. The pneumatic blower was sprayed for 1 second. Measurements were repeated 10 times. RESULTS: The DeVilbiss insufflator delivered the lowest mean BA dose, 6.1 mg (SD 3.4, range 2.1-13.7), followed by the House-Sheehy 8.9 mg (SD 8.4, range 1.6-27.8), the pneumatic blower 192.8 mg (SD 38.3, range 150.0-261.7), and the accordion, 284.1 mg (SD 215.0, range 37.8-730.8). CONCLUSION: BA dose delivery is highly variable by insufflator type, and doses thought to cause systemic toxicity are commonly generated. Awareness of and further investigation into the potential toxicity of otic administration of BA seems warranted.

Boric acid was orally toxic to different instars of Blattella germanica (L.) (Blattodea: Blattellidae) and caused dysbiosis of the, gut microbiota.

Boric acid, a well-established chemical insecticide, has a good control effect on various types of cockroaches. In this study, we investigated the oral virulence effect of boric acid on German cockroach (Blattella germanica) of various instars and characterized its effect on the gut microbiota by high-throughput sequencing technology. The results of an oral toxicity test showed that the toxicity of boric acid was positively correlated with its concentration and negatively correlated with the instar of cockroach nymphs. The 1-3 instar nymphs showed the strongest sensitivity to boric acid, which exhibited a median lethal time of only 3.16 d, while the 6-7 instar nymphs showed the weakest sensitivity, and exhibited a median lethal time of 10.15 d. There was no significant difference between male and female insects regarding their sensitivity to boric acid. Oral treatment of boric acid resulted in severe dysbiosis in cockroaches, the relative abundances of Bacteroides, which can degrade a variety of complex macromolecules, and Enterococcus, which can inhibit pathogenic microorganisms, were significantly reduced, while the relative abundance of the opportunistic pathogenic bacterium Weissella was significantly increased. It was speculated that dysbiosis of gut microbiota might accelerate the toxicity of boric acid on German cockroaches.

Cytotoxic Effect of Boron Application on Glioblastoma Cells.

AIM: To investigate the cytotoxic effects of boron application at different doses on U-87 MG glioblastoma cells. MATERIAL AND METHODS: The T98G (ATCC® CRL-1690?) glioblastoma cell strain used in the study was acquired from the American Type Culture Collection (ATCC) (Manassas, USA). Boric acid solution was prepared by mechanical mixing in the medium. Afterwards, 2.5 mM, 25 mM and 50 mM boron were each added to U87-MG glioblastoma cells and incubated for 48 hours. The cytotoxic effects on the cells was determined using the MTT (Methylthiazole diphenyl tetrazolium) test 48 hours after boron application. RESULTS: IC50 value was detected as 17 mM in the 48-hour boric acid application on U-87 MG glioblastoma cells. CONCLUSION: Boron treatment might be an effective approach for glioblastoma.

Suitability of boric acid as a boron drug for boron neutron capture therapy for hepatoma.

Hepatoma is the second leading cause of cancer death worldwide. Due to the poor outcomes of patients with late diagnosis, newer treatments for hepatoma are still needed. As an emerging therapy, boron neutron capture therapy (BNCT) may be an effective solution in hepatoma management. In this study, boric acid (BA) was used as the boron drug for in vivo analysis of action mechanism. The N1S1 single liver tumor-bearing rat and the VX2 multifocal liver tumor-bearing rabbit models were used to investigate the retention status of BA in the tumor regions during BNCT. The autoradiographic examination showed BA can localize specifically not only in the hepatoma cells but also in tumor blood vessels. Our findings indicate that superior hepatoma targeting could be achieved in BA-mediated BNCT, which supports BA to be a suitable boron drug for BNCT for hepatoma.

Evaluation of the Cytotoxicity and Apoptotic Induction in Human Liver Cell Lines Exposed to Three Food Additives.

BACKGROUND: Rapid lifestyle, especially among people living in urban areas, has led to increasing reliance on the processed food market. Unfortunately, harmful effects caused by the excessive use of food additives in such type of industry are often neglected. OBJECTIVE: This proposal investigates in vitro cytotoxic and apoptotic effects of three food preservatives commonly consumed in daily meals; sodium sulphite, boric acid, and benzoic acid. METHODS: The effect of the three preservatives on cell viability was tested on two different cell lines; normal liver cell line THLE2 and human hepatocellular carcinoma cancer cell line HepG2 using MTT assay. Cell cycle arrest was measured using flow cytometry by propidium iodide. Measurement of expression levels of two central genes, p53 and bcl-2 that play key roles in cell cycle and apoptosis was carried out in HepG2 cells using real time-PCR. RESULTS: Although the effect was more significantly realized in the HepG2 cell line, the viability of both cell lines was decreased by all of the three tested compounds. Flow cytometric analysis of HepG2 cells treated with sodium sulphite, boric acid, and benzoic acid has revealed an increase in G2/M phase cell cycle arrest. In Sodium sulphite and boric acid-treated cells, expression levels of p53 were up-regulated, while that of the Bcl2 was significantly down-regulated. On the other hand, Benzoic acid has shown an anti-apoptotic feature based on the increased expression levels of Bcl-2 in treated cells. CONCLUSION: In conclusion, all of the tested compounds have decreased the cell line viability and induced both cell cycle arrest and apoptotic events indicating their high potential of being cytotoxic and genotoxic materials.

Ototoxicity of boric acid powder in a rat animal model / Ototoxicidade de ácido bórico em pó em um modelo animal de rato

Abstract Introduction: Boric acid, which has antiseptic and acidic properties, is used to treat external and middle ear infections. However, we have not found any literature about the effect of boric acid powder on middle ear mucosa and inner ear. Objective: The purpose of this study is to investigate possible ototoxic effects of boric acid powder on cochlear outer hair cell function and histological changes in middle ear mucosa in a rat animal model. Methods: Twenty healthy, mature Wistar albino rats were used in this study. The rats were divided into two groups, Group A and Group B, each of which consisted of 10 rats. Initially, the animals in each group underwent distortion product otoacoustic emissions testing of their right and left ears. After the first distortion product otoacoustic emissions test, a surgical microscope was used to make a small perforation in both ears of the rats in each group, and a second distortion product otoacoustic emissions test was used to measure both ears in all of the rats. Boric acid powder was applied to the right middle ear of the rats using tympanic membrane perforation, and the distortion product otoacoustic emissions were measured immediately after the boric acid powder application. The histological changes and distortion product otoacoustic emissions were evaluated three days later in Group A and 40 days later in Group B. Results: No significant differences were found at all of the distortion product otoacoustic emissions frequencies. In Group A, mild inflammation of the middle ear mucosa was found on the third day after boric acid powder application. In Group B, boric acid powder caused mild inflammatory changes on the 40th day, which declined over time. Those changes did not lead to significant fibrosis within the mucosa. Conclusion: In rats, boric acid powder causes mild inflammation in middle ear mucosa and it has no ototoxic effects on cochlear outer hair cell function in the inner ear of rats.

Resumo Introdução: O ácido bórico, que tem propriedades antissépticas e ácidas, é usado para tratar infecções de orelha externa e média. No entanto, não encontramos literatura sobre o efeito do ácido bórico em pó sobre a mucosa da orelha interna e da orelha média. Objetivo: Investigar possíveis efeitos ototóxicos do ácido bórico em pó sobre a função das células ciliadas externas cocleares e alterações histológicas na mucosa da orelha média em um modelo animal de rato. Método: Vinte ratos Wistar albinos maduros e saudáveis foram usados neste estudo. Os ratos foram divididos em dois grupos, Grupo A e Grupo B, cada um dos quais com 10 ratos. Inicialmente, os animais de cada grupo foram submetidos a testes de emissões otoacústicas - produto de distorção, nas orelhas direita e esquerda. Após o primeiro teste de emissões otoacústicas - produto de distorção, utilizou-se um microscópio cirúrgico para fazer uma pequena perfuração em ambas as orelhas dos ratos em cada grupo, e um segundo teste de emissões otoacústicas - produto de distorção foi utilizado para medir e avaliar as orelhas em todos os ratos. O ácido bórico em pó foi aplicado na orelha média direita dos ratos utilizando perfuração da membrana timpânica e as emissões otoacústicas - produto de distorção foram medidas imediatamente após a aplicação de ácido bórico em pó. As alterações histológicas e emissões otoacústicas - produto de distorção foram avaliadas três dias depois no Grupo A e 40 dias depois no Grupo B. Resultados: Não foram encontradas diferenças significativas em todas as frequências da emissões otoacústicas - produto de distorção. No Grupo A, foi observada uma ligeira inflamação da mucosa da orelha média no terceiro dia após a aplicação de ácido bórico em pó. No Grupo B, o ácido bórico em pó causou leves alterações inflamatórias após 40 dias, que diminuíram ao longo do tempo. Essas alterações não levaram à fibrose significativa da mucosa. Conclusão: Em ratos, o ácido bórico em pó causa inflamação leve na mucosa da orelha média e não tem efeitos ototóxicos na função das células ciliadas externas da cóclea na orelha interna.

Boric acid induces cytoplasmic stress granule formation, eIF2α phosphorylation, and ATF4 in prostate DU-145 cells.

Dietary boron intake is associated with reduced prostate and lung cancer risk and increased bone mass. Boron is absorbed and circulated as boric acid (BA) and at physiological concentrations is a reversible competitive inhibitor of cyclic ADP ribose, the endogenous agonist of the ryanodine receptor calcium (Ca(+2)) channel, and lowers endoplasmic reticulum (ER) [Ca(2+)]. Low ER [Ca(2+)] has been reported to induce ER stress and activate the eIF2α/ATF4 pathway. Here we report that treatment of DU-145 prostate cells with physiological levels of BA induces ER stress with the formation of stress granules and mild activation of eIF2α, GRP78/BiP, and ATF4. Mild activation of eIF2α and its downstream transcription factor, ATF4, enables cells to reconfigure gene expression to manage stress conditions and mild activation of ATF4 is also required for the differentiation of osteoblast cells. Our results using physiological levels of boric acid identify the eIF2α/ATF pathway as a plausible mode of action that underpins the reported health effects of dietary boron.

Reproductive toxicity parameters and biological monitoring in occupationally and environmentally boron-exposed persons in Bandirma, Turkey.

Boric acid and sodium borates have been considered as being "toxic to reproduction and development", following results of animal studies with high doses. Experimentally, a NOAEL (no observed adverse effect level) of 17.5 mg B/kg-bw/day has been identified for the (male) reproductive effects of boron in a multigeneration study of rats, and a NOAEL for the developmental effects in rats was identified at 9.6 mg B/kg-bw/day. These values are being taken as the basis of current EU safety assessments. The present study was conducted to investigate the reproductive effects of boron exposure in workers employed in boric acid production plant in Bandirma, Turkey. In order to characterize the external and internal boron exposures, boron was determined in biological samples (blood, urine, semen), in workplace air, in food, and in water sources. Unfavorable effects of boron exposure on the reproductive toxicity indicators (concentration, motility, morphology of the sperm cells and blood levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone) were not observed. The mean calculated daily boron exposure (DBE) of the highly exposed group was 14.45 ± 6.57 (3.32-35.62) mg/day. These human exposures represent worst-case exposure conditions to boric acid/borates in Turkey. These exposure levels are considerably lower than exposures, which have previously led to reproductive effects in experimental animals. In conclusion, this means that dose levels of boron associated with developmental and reproductive toxic effects in animals are by far not reachable for humans under conditions of normal handling and use.

Micro-computed tomography and alizarin red evaluations of boric acid-induced fetal skeletal changes in Sprague-Dawley rats.

BACKGROUND: Assessment of developmental toxicity has historically included assessment of fetal skeletal morphology after alizarin red staining. X-ray micro-computed tomography (micro-CT) produces high-resolution images of skeletal structures and was investigated as an alternative method. METHODS: Groups of 5 mated Crl:CD (SD) female rats each were administered vehicle or boric acid (40 to 500 mg/kg/day) from GD 6 through 11. On GD 21, all live fetuses were weighed, euthanized, and viscera removed. Each litter was placed into a custom-made polystyrene holder and scanned in the micro-CT imaging system. Raw projection data were acquired in approximately 15 sec ( approximately 20 litters per hour) and reconstructed images at 100-micron cubic voxel dimension could be viewed as early as 20 min later. Fetuses were subsequently stained with alizarin red, and findings recorded separately for each method without knowledge of treatment group. RESULTS: Micro-CT evaluation of fetal rat skeletons detected essentially the same skeletal malformations, variations, and incomplete ossifications as seen by the staining method. The specific skeletal abnormalities that did not match exactly involved the smallest skeletal elements with minimal degrees of ossification (i.e., cervical ribs, hypoplastic 13(th) ribs, supernumerary ribs, the 5(th) sternebra, and numbers of caudal vertebrae), but the differences did not impact the overall conclusions. Additional measures such as femur length were easily measured by micro-CT. CONCLUSIONS: These results indicate that micro-CT imaging can effectively assess rat fetal skeletal structures, and for those laboratories with this resource, it may be used to significantly reduce time prior to skeletal evaluation and hazardous wastes associated with staining.

Boric acid inhibits stored Ca2+ release in DU-145 prostate cancer cells.

Boron (B) is a developmental and reproductive toxin. It is also essential for some organisms. Plants use uptake and efflux transport proteins to maintain homeostasis, and in humans, boron has been reported to reduce prostate cancer. Ca2+ signaling is one of the primary mechanisms used by cells to respond to their environment. In this paper, we report that boric acid (BA) inhibits NAD+ and NADP+ as well as mechanically induced release of stored Ca2+ in growing DU-145 prostate cancer cells. Cell proliferation was inhibited by 30% at 100 microM, 60% at 250 microM, and 97% at 1,000 microM BA. NAD+-induced Ca2+ transients were partly inhibited at 250 microM BA and completely at 1,000 microM BA, whereas both NADP+ and mechanically induced transients were inhibited by 1,000 microM BA. Expression of CD38 protein increased in proportion to BA exposure (0-1,000 microM). In vitro mass spectrometry analysis showed that BA formed adducts with the CD38 products and Ca2+ channel agonists cyclic adenosine diphosphate ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). Vesicles positive for the Ca2+ fluorophore fluo-3 acetoxymethyl ester accumulated in cells exposed to 250 and 1,000 microM BA. The BA analog, methylboronic acid (MBA; 250 and 1,000 microM), did not inhibit cell proliferation or NAD+, NADP+, or mechanically stimulated Ca2+ store release. Nor did MBA increase CD38 expression or cause the formation of intracellular vesicles. Thus, mammalian cells can distinguish between BA and its synthetic analog MBA and exhibit graded concentration-dependent responses. Based on these observations, we hypothesize that toxicity of BA stems from the ability of high concentrations to impair Ca2+ signaling.

Boric acid inhibits embryonic histone deacetylases: a suggested mechanism to explain boric acid-related teratogenicity.

Histone deacetylases (HDAC) control gene expression by changing histonic as well as non histonic protein conformation. HDAC inhibitors (HDACi) are considered to be among the most promising drugs for epigenetic treatment for cancer. Recently a strict relationship between histone hyperacetylation in specific tissues of mouse embryos exposed to two HDACi (valproic acid and trichostatin A) and specific axial skeleton malformations has been demonstrated. The aim of this study is to verify if boric acid (BA), that induces in rodents malformations similar to those valproic acid and trichostatin A-related, acts through similar mechanisms: HDAC inhibition and histone hyperacetylation. Pregnant mice were treated intraperitoneally with a teratogenic dose of BA (1000 mg/kg, day 8 of gestation). Western blot analysis and immunostaining were performed with anti hyperacetylated histone 4 (H4) antibody on embryos explanted 1, 3 or 4 h after treatment and revealed H4 hyperacetylation at the level of somites. HDAC enzyme assay was performed on embryonic nuclear extracts. A significant HDAC inhibition activity (compatible with a mixed type partial inhibition mechanism) was evident with BA. Kinetic analyses indicate that BA modifies substrate affinity by a factor alpha=0.51 and maximum velocity by a factor beta=0.70. This work provides the first evidence for HDAC inhibition by BA and suggests such a molecular mechanism for the induction of BA-related malformations.

Boric acid enhances in vivo Ehrlich ascites carcinoma cell proliferation in Swiss albino mice.

The influence of boric acid, a boron carrier, on Ehrlich ascites carcinoma (EAC) cell-bearing mice was investigated in view of its importance in the boron neutron capture therapy and the influence of boron on proliferation and progression of cancer cells mediated by proteoglycans and collagen. The present study included the evaluation of boric acid for the effects on total count and viability of EAC cells in addition to their non-protein sulfhydryls (NP-SH) and malondialdehyde (MDA) contents as parameters for conjugative detoxication potency and possible oxidative damage. The EAC cell-bearing animals were also observed for the effect on survival, body weight changes, and histopathological evaluation of the tumors grown at the site of inoculation. The treatment with boric acid significantly increased the total number of peritoneal EAC cells and their viability. A significant increase in the body weight was observed that dose-dependently reached plateau levels by 20 days of treatment. Conversely, a reduction in the duration of survival of these animals was evident with the same protocol. Boric acid treatment resulted in a decrease in NP-SH contents with a concomitant increase in MDA levels in EAC cells as revealed by the results of the biochemical analysis. These data are supported by our results on histopathological investigations, which apparently showed fast growth, in addition to several mitotic figures and mixed inflammatory reaction, after treatment with boric acid. It seems likely that a particular combination of properties of boric acid, rather than a single characteristic alone, will provide useful information on the use of this boron carrier in neutron capture therapy.

Evaluation of a reproductive toxicity assay using Xenopus laevis: boric acid, cadmium and ethylene glycol monomethyl ether.

Cadmium (Cd), boric acid (BA) and ethylene glycol monomethyl ether (EGME) were evaluated for reproductive and developmental toxicity in Xenopus laevis. Eight reproductively mature adult male and eight superovulated female Xenopus laevis were exposed to at least five separate sublethal concentrations of each material via the culture water for a period of 30 days. Four respective pairs were mated and the offspring evaluated for developmental effects; an evaluation of reproductive status was performed on the remaining four specimens. Ovary pathology, oocyte count, oocyte maturity and maturation capacity (germinal vesicle breakdown, GVBD) and necrosis were evaluated in the female, whereas testis pathology, sperm count, dysmorphology and motility were studied in the male. Based on this assessment, each test material exerted reproductive toxicity in Xenopus laevis, but with varying potencies. Adult female exposure to Cd and EGME particularly, and to a lesser extent to BA, resulted in transgenerational toxicity to the developing progeny. Further, this model appears to be a useful tool in the initial assessment and prioritization of potential reproductive toxicants for further testing.

Toxic effects of boric acid on the German cockroach.

Boric acid is a slow-acting, inorganic insecticide whose mode of action has not been satisfactorily elucidated. Reported here is evidence which shows that ingested boric acid destroys the cellular lining of the foregut of German cockroaches, Blattella germanica (L.). This effect appears to be sufficient to bring about the death of the insects, perhaps ultimately by starvation. This finding is important because resistance to conventional insecticides may re-establish boric acid as a prominent cockroach control chemical.

Toxicity and carcinogenicity studies of boric acid in male and female B6C3F1 mice.

Toxicity and potential carcinogenicity studies of boric acid were investigated in mice to verify in a second rodent species that this was a noncarcinogenic chemical. Earlier chronic studies in rats indicated boric acid was not a carcinogen. The chemical is nominated for testing because over 200 tons are produced annually, there are multiple uses for the product, and there is potential for widespread human exposure, both orally and dermally. Both sexes of B6C3F1 mice were offered diets mixed with boric acid for 14 days, 13 weeks, or 2 years. Dietary doses used in the acute, 14-day study were 0, 0.62, 1.25, 2.5, 5, and 10%; those in the subchronic, 13-week study were 0, 0.12, 0.25, 0.50, 1, and 2%; and doses in the 2-year, chronic study were 0, 0.25, and 0.50% in the diet. Mortality, clinical signs of toxicity, estimates of food consumption, body weight gain, and histopathologic examination of selected tissues constituted the variables measured. In the 14-day study mortality was proportional to dose and time of exposure in both sexes, occurring in dose groups as low as 2.5% and as early as 7 days of exposure. Body weights were depressed more than 10% below controls in the higher dose groups of both sexes. Mortality in the 13-week study was confined to the two highest dose groups in male mice and to the 2%-dose group in females. Body weight depression from 8 to 23% below those of controls occurred in the 0.50% and higher dose groups of both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of the testicular toxicity of boric acid in rats: in vivo and in vitro studies.

High-dose boric acid (BA) exposure produces testicular lesions in adult rats characterized by inhibited spermiation (IS) that may progress to atrophy. In vivo and in vitro studies addressed possible mechanisms. In vivo, boron tissue disposition was examined, since no detailed data existed, and relevant boron concentrations for in vitro studies needed to be set. Since BA induces riboflavinuria and also affects calcium/phosphorus homeostasis, and testis zinc appears essential for normal testis function, we examined BA effects on flavin status and testis levels of phosphorus (P), calcium (Ca) and zinc (Zn). Data showed that the testicular toxicity and central nervous system (CNS) hormonal effect were not due to selective boron accumulation in testis or brain/hypothalamus, with testis boron concentrations at approximately 1 to 2 mM; that riboflavin deficiency is not involved, due to both the absence of overt signs of deficiency and effects on tissue flavin content during BA exposure; and that changes in testis P, Ca and Zn levels did not precede atrophy, and are therefore unlikely to be mechanistically relevant. In vitro studies addressed the hallmarks of the BA testicular toxicity: the mild hormone effect, the initial IS, and atrophy. No effect of BA on the steroidogenic function of isolated Leydig cells was observed, supporting the contention of a CNS-mediated rather than a direct hormone effect. Since increased testicular cyclic adenosine monophosphate (cAMP) produces IS, and a role for the serine proteases plasminogen activators (PAs) in spermiation has been proposed, we examined in vitro BA effects on both Sertoli cell cAMP accumulation and PA activity, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of boric acid (BA) on testicular cells in culture.

High-dose boric acid (BA) exposure produces testicular lesions in adult rats characterized by inhibited spermiation that may progress to nonrecoverable atrophy. The mechanism for the testicular toxicity of BA is unknown. To examine possible direct effects, the present study evaluated selected aspects of various testicular cell culture systems after in vitro BA exposure. Specifically, the hallmarks of the BA testicular toxicity were addressed: the mild hormone effect, the initial inhibition of spermiation, and atrophy. No effect of BA on the steroidogenic function of isolated Leydig cells was observed, supporting the contention of a CNS-mediated rather than a direct hormone effect. Since increased testicular cyclic AMP (cAMP) produces inhibited spermiation, and a role for the serine proteases plasminogen activators (PAs) in spermiation has been proposed, we evaluated both Sertoli cell cAMP accumulation in Sertoli-germ cell cocultures and the stage-specific secretion of PA activity in cultured seminiferous tubules after in vitro BA exposure, respectively. The results showed that the inhibited spermiation is not due to BA effects on either process. To address the atrophy, we evaluated BA effects in Sertoli-germ cell cocultures on 1) morphology/germ cell attachment, which might identify a target cell; 2) Sertoli cell energy metabolism, because lactate, secreted by Sertoli cells, is a preferred energy source for germ cells; and 3) DNA/RNA synthesis, because germ cells synthesize DNA/RNA and BA impairs nucleic acid synthesis in liver and may do so in testis. Despite the absence of overt morphologic changes and germ cell loss, the most sensitive in vitro endpoint was DNA synthesis of mitotic/meiotic germ cells, with energy metabolism in Sertoli or germ cells affected to a lesser extent. A re-evaluation of testis sections from rats exposed to BA revealed a decrease in the early germ cell/Sertoli cell ratio prior to atrophy. Thus, although the mechanism for the inhibited spermiation is still undefined and is the subject of future work, these combined studies revealed some changes offering a plausible explanation for the atrophy aspect of the BA testicular lesion.

Development of testicular lesions in F344 rats after treatment with boric acid.

Boric acid is an inorganic acid that impairs fertility in male rodents. A reproductive assessment by continuous breeding study found that male rats treated with boric acid had decreased fertility and sperm motility. In order to determine the cell type that is first affected by boric acid, we have examined the development of the boric acid-induced testicular lesion by light and electron microscopy. Adult F344 male rats were fed 9000 ppm boric acid in NIH-07 rat chow for up to 4 weeks. The first testicular lesion noted was an inhibition of spermiation, which appeared by Day 7. Widespread exfoliation of apparently viable germ cells, and pachytene cell death in stages VII and XIV, appeared as exposure continued. After 28 days of dosing, extreme epithelial disorganization and germ cell loss were evident. To determine if there was a hormonal component to the boric acid-induced testicular lesion, serum levels of basal, hCG-, and LHRH-stimulated testosterone levels were measured. After 4 days of dosing, basal testosterone levels were lower than controls and remained low during dosing. However, serum testosterone levels were similar in both boric acid-treated and control animals after either hCG or LHRH challenge. To determine if boron was preferentially accumulated by the testis, boron levels in testis, epididymis, liver, kidney, and blood were measured. Boron levels had effectively reached steady-state levels by Day 4 and were not differentially concentrated in the tissues examined. Thus, these studies characterize the testicular lesion produced by boric acid exposure and identify a decrease in basal serum testosterone levels in the absence of selective accumulation of boron in the testis.

Experimental chelation therapy in chromium, lead, and boron intoxication with N-acetylcysteine and other compounds.

The usefulness of N-acetylcysteine (NAC) as a chelating agent was studied for the toxin potassium dichromate, lead tetraacetate, and boric acid. Mature Sprague-Dawley rats were intoxicated with these substances and placed in metabolic cages. Urinary excretion rates of intoxicant and total urine volume were determined during treatment with N-acetylcysteine, calcium EDTA, and/or dimercaptosuccinic acid, N-acetylcysteine proved to be the most effective agent at increasing the excretion of chromium and boron and was also able to reverse the oliguria associated with these toxins. Dimercaptosuccinic acid was most effective at the chelation of lead. NAC did not increase the excretion of lead. We conclude that NAC may be useful in intoxications due to chromate and borate and is effective at reversing the oliguria associated with these intoxicants.