Implementation of an in vitro methodology for phototoxicity evaluation in a human keratinocyte cell line.

To assess photoxicity, several in vitro methods using different cellular models have been developed for preclinical testing. Over prediction of the in vivo photosafety hazard has been however appointed. Herein, we describe the implementation and validation of an in vitro methodology for phototoxicity evaluation based on the 3T3 neutral red uptake phototoxicity test using the HaCaT human keratinocyte cell line, and UVA/UVB radiation. Known positive (5-methoxypsoralen, chlorpromazine, and quinine) and negative (acetyl salicylic acid, hexachlorophene, and sodium lauryl sulphate) controls were tested together with a set of chemical currently used in cosmetic/pharmaceutical formulations. Apart from the advantage of using a cell line of human origin, these cells were generally more resistant to the cytotoxic effects of the test substances relative to the 3T3 mouse fibroblasts when exposed to an UVA irradiation dose of 1.7 mW/cm2. Therefore, this HaCaT NRU assay provides a more realistic experimental model that overcomes the over/high sensitivity frequently noted with the 3T3 NRU assay and that is more consistent with the human in vivo situation. Using a more representative method can prevent time-consuming and expensive in vivo testing in both animal models and humans that can significantly delay the clinical development of new chemicals.

Co-nanoencapsulation of antimalarial drugs increases their in vitro efficacy against Plasmodium falciparum and decreases their toxicity to Caenorhabditis elegans.

Drugs used for the treatment and prevention of malaria have resistance-related problems, making them ineffective for monotherapy. If properly associated, many of these antimalarial drugs may find their way back to the treatment regimen. Among the therapeutic arsenal, quinine (QN) is a second-line treatment for uncomplicated malaria but has side effects that limit its use. Curcumin (CR) is a natural compound with anti-plasmodial activities and low bioavailability. In this context, the aim of this work was to develop and characterize co-encapsulated QN + CR-loaded polysorbate-coated polymeric nanocapsules (NC-QC) to evaluate their activity on Plasmodium falciparum and the safety of the nanoformulations for Caenorhabditis elegans. NC-QC displayed a diameter of approximately 200 nm, a negative zeta potential and a slightly basic pH. The drugs are homogeneously distributed in the NCs in the amorphous form. Co-encapsulated NCs exhibited a significant reduction in P. falciparum parasitemia, better than QN/CR. The worms exposed to NC-QC showed higher survival and longevity and no decrease in their reproductive capacity compared to free and associated drugs. It was possible to prove that the NCs were absorbed orally by the worms using fluorescence microscopy. Co-encapsulation of QN and CR was effective against P. falciparum, minimizing the toxic effects caused by chronic exposure of the free drugs in C. elegans.

Maternal consumption of quinine-containing sodas may induce G6PD crises in breastfed children.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect often presenting with neonatal jaundice and/or hemolytic anemia. G6PD hemolytic events are linked with exposure to a pro-oxidant agent. We here report three cases of initial G6PD crises in breastfed children secondary to maternal consumption of a tonic drink which contains quinine. Quinine was found in breast milk of one of the mothers after she consumed tonic water. CONCLUSION: The amount of quinine that is transmitted through breast milk appears to be sufficient to induce G6PD crises in breastfed children. We hence recommend that consumption of quinine-containing sodas during breastfeeding should be avoided in populations with a high prevalence of G6PD deficiency. What is Known: • G6PD hemolytic events are linked with exposure to a pro-oxidant agent. • Ingestion of fava beans by a mother who was breastfeeding has been reported to induce a neonatal G6PD crisis. What is New: • Maternal consumption of tonic drink which contains quinine appears to be sufficient to induce G6PD crises in breastfed children. • Maternal consumption of quinine-containing sodas during breastfeeding should be avoided in populations with a high prevalence of G6PD deficiency.

Effective anti-leishmanial activity of minimalist squaramide-based compounds.

In order to evaluate the in vitro leishmanicidal activity of N,N'-Squaramides derivatives, compounds that feature both hydrogen bond donor and acceptor groups and are capable of multiple interactions with complementary sites, against Leishmania infantum, Leishmania braziliensis and Leishmania donovani a series of 18compounds was prepared and assayed on extracellular and intracellular parasite forms. Infectivity and cytotoxicity tests were performed on J774.2 macrophage cells using meglumine antimoniate (Glucantime) as the reference drug. Changes in metabolite excretion by 1H-NMR and the ultrastructural alterations occurring in the parasites treated using transmission electron microscopy (TEM), was analyzed. Compounds 1, 7, 11, 14 and 17 were the more active and less toxic. Infection rates showed that the order of effectiveness was 17 > 11 > 14 > 7 for both L. infantum and L. braziliensis and in the same way, the compound 1 for L. donovani. All these compounds have altered the typical structure of the promastigotes, glycosomes and mitochondria. These severe modifications by the compounds are the ultimate reasons for the alterations observed in the excretion products. The Squaramide 17 (3-(butylamino)-4-((3-(dimetilamino)propyl)(methyl)amino)cyclobut-3-en-1,2-dione) was clearly the most efficient of all compounds. The data appear to confirm that the severe modifications generated in organelles such as glycosomes or mitochondria by the compounds are the ultimate reasons for the alterations observed in the excretion products of all species. The activity, stability, low cost of starting materials, and straightforward synthesis make amino squaramides appropriate molecules for the development of an affordable anti-leishmanial agent.

The Use of the Schizonticidal Agent Quinine Sulfate to Prevent Pond Crashes for Algal-Biofuel Production.

Algal biofuels are investigated as a promising alternative to petroleum fuel sources to satisfy transportation demand. Despite the high growth rate of algae, predation by rotifers, ciliates, golden algae, and other predators will cause an algae in open ponds to crash. In this study, Chlorella kessleri was used as a model alga and the freshwater rotifer, Brachionus calyciflorus, as a model predator. The goal of this study was to test the selective toxicity of the chemical, quinine sulfate (QS), on both the alga and the rotifer in order to fully inhibit the rotifer while minimizing its impact on algal growth. The QS LC50 for B. calyciflorus was 17 µM while C. kessleri growth was not inhibited at concentrations <25 µM. In co-culture, complete inhibition of rotifers was observed when the QS concentration was 7.7 µM, while algal growth was not affected. QS applications to produce 1 million gallons of biodiesel in one year are estimated to be $0.04/gallon or ~1% of Bioenergy Technologies Office's (BETO) projected cost of $5/gge (gallon gasoline equivalent). This provides algae farmers an important tool to manage grazing predators in algae mass cultures and avoid pond crashes.

Development of a model for robust and exploratory analysis of the rodent brief-access taste aversion data.

The rodent brief-access taste aversion (BATA) model is an efficient in vivo screening tool for taste assessment. A new E(max) (maximum effect attributable to the drug) model was developed and further investigated in comparison with three previously published models for analysing the rodent BATA data; the robustness of all the models was discussed. The rodent BATA data were obtained from a series of experiments conducted with a bitter reference compound, quinine hydrochloride dihydrate (QHD). A new E(max) model that could be applied to both "lick numbers" and "lick ratios" was built and three published models that used lick ratios were employed for analysing the BATA data. IC50, the concentration that inhibits 50% of the maximum lick numbers, quantified the oral aversiveness of QHD. One thousand bootstrap datasets were generated from the original data. All models were applied to estimate the confidence intervals of the IC50s without symmetric assumption. The IC50 value obtained from the new E(max) model was 0.0496 mM (95% CI 0.0297-0.0857) using the lick numbers for analysis, while an IC50 of 0.0502 mM (95% CI 0.0267-0.0859) was acquired with the lick ratios. Except one published model, the IC50 values have a similar range for the 95% CI. The new E(max) model enabled the analysis of both "lick numbers" and "lick ratios" whereas other models could only handle data presented as "lick ratios". IC50s obtained with these two types of datasets showed similarity among all models thereby justified the robustness of the new E(max) model.

Toxins induce 'malaise' behaviour in the honeybee (Apis mellifera).

To avoid poisoning and death when toxins are ingested, the body responds with a suite of physiological detoxification mechanisms accompanied by behaviours that in mammals often include vomiting, nausea, and lethargy. Few studies have characterised whether insects exhibit characteristic 'malaise-like' behaviours in response to intoxication. Here, we used the honeybee to investigate how intoxication produced by injection or ingestion with three toxins with different pharmacological modes of action quinine, amygdalin, and lithium chloride affected behaviour. We found that toxin-induced changes in behaviour were best characterised by more time spent grooming. Bees also had difficulty performing the righting reflex and exhibited specific toxin-induced behaviours such as abdomen dragging and curling up. The expression of these behaviours also depended on whether a toxin had been injected or ingested. When toxins were ingested, they were least 10 times less concentrated in the haemolymph than in the ingested food, suggesting that their absorption through the gut is strongly regulated. Our data show that bees exhibit changes in behaviour that are characteristic of 'malaise' and suggest that physiological signalling of toxicosis is accomplished by multiple post-ingestive pathways in animals.

Effects of MHRA drug safety advice on time trends in prescribing volume and indices of clinical toxicity for quinine.

AIMS: To ascertain the effects of the Medicines and Healthcare products Regulatory Agency's (MHRA) safety update in June 2010 on the volume of prescribing of quinine and on indices of quinine toxicity. METHODS: We analysed quarterly primary care total and quinine prescribing data for England and quinine prescribing volume for individual Primary Care Trusts in the North East of England from 2007/8 to 2011/12 obtained from the ePACT.net database. We also analysed quinine toxicity enquiries to the National Poisons Information Service (NPIS) via Toxbase(®) and by telephone between 2004/5 and 2011/12. Joinpoint regression and Pearson's correlation tests were used to ascertain changes in trends in prescribing and indices of toxicity and associations between prescribing and indices of toxicity, respectively. RESULTS: Total prescribing continued to increase, but annual growth in quinine prescribing in England declined from 6.0 to -0.6% following the MHRA update [difference -0.04 (95% confidence interval -0.07 to -0.01) quinine prescriptions per 100 patients per quarter, P = 0.0111]. Much larger reductions were observed in Primary Care Trusts that introduced comprehensive prescribing reviews. The previously increasing trend in Toxbase(®) quinine searches was reversed [difference -19.76 (95% confidence interval -39.28 to -9.20) user sessions per quarter, P = 0.0575]. Telephone enquiries to NPIS for quinine have declined, with stabilization of the proportion of moderate to severe cases of quinine poisoning since the update. CONCLUSIONS: The MHRA advice was followed by limited reductions in the growth in quinine prescribing and in indicators of quinine overdose and toxicity. Quinine prescribing, however, remains common, and further efforts are needed to reduce availability and use.

Quercetin protects against testicular toxicity induced by chronic administration of therapeutic dose of quinine sulfate in rats.

BACKGROUND: Quinine, a rapidly acting blood schizonticide with a long history of use for the treatment of malaria, is gradually been implicated in reproductive toxicity. METHODS: In this study, testicular and spermatotoxic effects of quinine sulfate (QS) following treatment with an oral dose of 10 mg/kg/day (normal therapeutic dose) for 8 weeks was investigated in male albino rats. Toxicity was evaluated by assessing antioxidant defense capacity and markers of oxidative stress and testicular dysfunction in the testes and epididymal sperm. The possible ameliorative effect of quercetin (QC), when co-administered with QS, was also assessed. RESULTS: Administration of QS induced oxidative stress in rats. The activities of superoxide dismutase, catalase, and malondialdehyde (a marker of lipid peroxidation) increased (p<0.05) both in the testes and epididymal sperm following QS treatment when compared with saline-treated (control) rats. Ascorbic acid levels were significantly reduced, with an insignificant decrease in glutathione and testosterone levels in the QS-treated rats, when compared with control. The spermiogram decreased with increase in total sperm abnormalities in QS-treated rats and was associated with histopathological changes. Our results revealed that QC significantly ameliorated QS-induced testicular toxicity and oxidative stress. CONCLUSIONS: The testicular toxicity of QS is in part due to impairment of testicular antioxidant defense, spermatogenesis and enhancement of lipid peroxidation. Also, the ability of QC to reverse the deleterious effects of QS on the testes and epididymis qualifies it as a potent chemo-protective agent against QS-induced reproductive toxicity.

Comparative study of chloroquine and quinine on malaria rodents and their effects on the mouse testis.

OBJECTIVE: To evaluate the effects of quinine and chloroquine against male mice infected with Plasmodium berghei and their adverse effects on the mice testes. METHODS: In this study, 48 adult male mice, (20-25 g), aged 8 to 12 weeks were divided into four groups. This study was carried out from December 2009 until May 2010 in the School of Public Health, Tehran University of Medical Sciences. RESULTS: The results showed that 58.33% of mice treated with chloroquine were completely recovered. Parasitemia was 4% on day 8 when compared to that on day 0, whereas it was 9% on day 9. There was no orchitis found in this group. The mortality of mice after exposing to quinine on day 5 was 8.3%, whereas from day 10 to day 14 it was 91.7%. We found 75% orchitis occurred in quinine treated group. There was a significant difference between quinine and chloroquine effects on the parasite and also mice testes (P<0.05). CONCLUSIONS: In this study, It can be concluded that male mice have full resistance to the quinine. Quinine does not only make male mice recover completely, but also cause inflammation on mice testicles tissue.

Differential effects of salicylate, quinine, and furosemide on Guinea pig inner and outer hair cell function revealed by the input-output relation of the auditory brainstem response.

BACKGROUND: Sensory hearing loss is predominantly caused by the destruction of cochlear outer hair cells (OHCs), inner hair cells (IHCs), or spiral ganglion cells (SGCs). There have been a number of attempts to differentiate between these etiologies of hearing loss, using various psychoacoustic and physiologic paradigms. PURPOSE: Here we investigate the potential of the auditory brainstem response (ABR) input/output function for such differential diagnosis. On the basis of the saturation of the OHC-based cochlear amplifier, it was hypothesized that selective impairment of OHCs would reduce ABR amplitudes at low to moderate but not at high sound levels. Selective impairment of IHCs or SGCs would reduce ABR amplitudes more or less uniformly across sound level. Finally, a mix of OHC and IHC or SGC impairment would reduce ABR amplitudes at all sound levels but less so at high levels depending on the relative contribution of OHC impairment to the hearing loss. RESEARCH DESIGN: To test these hypotheses, normal-hearing adult guinea pigs were intravenously injected with either salicylate, furosemide, or quinine, under ketamine anesthesia. ABRs, as well as distortion-product otoacoustic emissions (DPOAEs), were measured as a function of the sound stimulus level before and after drug injection. RESULTS: Following salicylate injection, ABR amplitudes were reduced only at low-moderate stimulus levels. Following furosemide or quinine injection, ABR amplitudes were reduced at all levels but less so at high ones. This is in accord with the expectation that acute salicylate administration selectively affects the OHCs, while furosemide and quinine affect both OHCs and IHCs/SGCs. Such differential diagnosis was not possible solely on the basis of DPOAE amplitudes, which were unchanged at high stimulus levels after the injection of each of the three drugs. Comparison of ABR and DPOAE threshold shifts could also differentiate the effects of salicylate from those of furosemide and quinine but could not, for example, unequivocally point to salicylate's selective impairment of OHCs. CONCLUSIONS: ABR amplitudes appear suitable for differentiating between damage to OHCs and IHCs/SGCs, at least in a controlled experimental setting where pre- and postmanipulation data are available. This could be useful for noninvasively testing the effects of drugs or acoustic overstimulation on the cochlea, at least in the laboratory. Clinical applicability would seem to be limited by the high variability in ABR amplitudes among normal-hearing humans but might be feasible in the future if regular ABR testing entered into routine clinical practice.

Photopatch testing negative in systemic quinine phototoxicity.

Drug-induced phototoxicity can be caused by topical or systemic agents and is diagnosed on the basis of clinical history, examination and appropriate investigations. Photopatch testing is the investigation of choice for topical photocontact allergic dermatitis, but its use in drug-induced phototoxicity has not been validated. We retrospectively analyzed the results of photopatch testing to the drug quinine sulfate in three patients in whom a diagnosis of drug-induced phototoxicity to this agent had been made. None of the three patients had positive photopatch test reactions at any time point. This demonstrates that in our patients, photopatch testing to quinine sulfate was not a useful additional investigation for diagnosing drug-induced phototoxicity.

Dermatitis alérgica de contacto a quinina por una loción capilar anticaída / Contact allergic dermatitis to quinine in an anti-hair loss lotion

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A behavioural operant discrimination model for assessment and pharmacological manipulation of visual function in rats.

A large number of commercially available drugs are known to cause visual side effects in humans. Therefore, it would be advantageous to screen for alterations in visual function at a pre-clinical stage. Available methods, however, lack control for motivational and motoric side effects. The aim of the present study was therefore to develop a behavioural test to detect and quantify drug-induced visual side effects while simultaneously controlling for other side effects. We here present a novel model based on operant conditioning methodology with a food rewarded two-choice design to assess visual acuity and contrast sensitivity in rats. Rats were trained to discriminate between computer-generated sine-wave gratings and homogenous grey stimuli of equal luminance. They were subsequently tested with novel stimuli differing to training stimuli according to either spatial frequency or contrast. Finally, we tested how visual acuity was affected by oral administration of quinine HCl, a compound known to affect visual function in man. The rats learned to discriminate visual stimuli within 4-5weeks of twice daily training. A training procedure with moving stimuli achieved faster learning than with static stimuli. The visual detection threshold for discrimination of grating patterns decreased as a function of the contrast level, ranging from a spatial frequency of 0.8cycles/degree (c/d) at 100% contrast to 0.2c/d at 12.5%. Administration of quinine HCl was shown to affect the visual acuity threshold in a dose- and time dependent manner. In addition, response rate was affected by quinine administration but temporally isolated from the attenuation of visual acuity demonstrating that this model can separate the visual effects from motoric and motivational side effects.

La quinina y sus posibles implicaciones toxicológicas: análisis de aguas tónicas en España / Quinine potential toxicological implications: Analysis of tonic waters in Spain

Fundamento: La quinina es un alcaloide presente de forma natural en la corteza de algunos árboles del género Rubiaceae, empleándose tradicionalmente para el tratamiento de la malaria, convulsiones y diversas infecciones. En este trabajo presentamos los resultados de muestras analizadas en España, tanto de la concentración hallada como las normas relativas a su etiquetado, así como brevemente las posibles implicaciones en la salud pública que tiene la quinina. Método: Se ha analizado el contenido de quinina en un total de 11 muestras de diferentes fabricantes adquiridas en tiendas locales de España mediante cromatografía líquida acoplada a la detección mediante fluorescencia inducida por láser. Resultados: El método empleado se caracteriza por su precisión, rapidez y sensibilidad. No hay una concentración homogénea de quinina en las bebidas analizadas. El etiquetado no indica el contenido en quinina Conclusiones: Creemos necesario una regulación más especifica y mayor información para los consumidores, especialmente para ciertos grupos de riesgo(AU)

Background: Quinine is an alcaloide naturally occuring in the crust of some trees of genus Rubiaceae, traditionally used for the treatment of malaria, seizures, and various infections. In this work we present results of samples tested in Spain, both of the concentration foundand labelling, as well as related to the potential implications of quinine on public health. Methods: The content of quinine was analyzed in 11 samples of tonic waters in the Spanish market by liquid chromatography coupled through laser induced fluorescence detection. Results: The method used is characterized by its accuracy, speed and sensitivity. Quinine concentration in beverages is not homogeneous. The labelling does not indicate the quinine content. Conclusions: More specific regulation is needed as well as more information to consumers, especially for certain risk groups(AU)

Aspectos toxicológicos del consumo de bebidas refrescantes que contienen quinina / Toxicological aspects of the consumption of soft drinks containing quinine

En España, la producción total de bebidas refrescantes en 2005 ascendió a 4.887 millones de litros. Estos datos representan un incremento del 2,5 % con respecto al año 2004. Del total de la producción industrial,98822 litros (2,02%) corresponden a bebidas refrescantes tipo tónica. En términos toxicológicos el consumo de quinina debe ser evitado por mujeres embarazadas, individuos con cuadro de fallo hepático y muy especialmente por niños. Se han descrito incluso episodios de alergias y shocks anafilácticos derivados de una única ingesta de esta sustancia. Ya el consumo de quinina en dosis excesivas, puede causar un cuadro de intoxicación reversible denominado cinchonismo. Creemos necesario una regulación más específica y mayor información para los consumidores, especialmente para ciertos grupos de riesgo. De los resultados de muestras analizadas en España, tanto de la concentración hallada como de las normas relativas a su etiquetado, se desprende que no hay una concentración homogénea de la substancia analizada, ni un cumplimiento de la legislación establecida (AU)

In Spain, total production of soft drinks in 2005 amounted to 4887 million liters. These, represent an increase of 2.5% compared to the year 2004. Of the total industrial output, 98,822 liters (2.02%) corresponding to soft drinks type tonic water. Toxicologically, quinine is important and should be avoided by pregnant women and people with hepatic failure, and remains a potentially extremely toxic agent in children. Also allergy to quinine and anaphylactic shock after drinking a glass of tonic water has been described. The use of quinine in therapeutic or excessive consumes may cause cinchonism syndrome. We believe there is a need for more extensive information for risk groups and to raise awareness among consumers about possible adverse reactions to quinine. Data show that quinine concentrations in the analyzed beverages from Spain is variable. Soft drinks from different manufactures do not always comply with the labelling directive (AU)

Capillary electrophoretic studies on the photogenotoxic potential of pharmaceutical substances.

Drug-induced phototoxic skin responses, including photoirritation, photoallergy and photogenotoxicity, are identified as adverse reactions. In this study, we attempted to develop effective analytical tools to predict the photogenotoxic potential of pharmaceutical substances with the use of pBR322 DNA, a plasmid DNA. pBR322 DNA was irradiated with simulated solar light in the presence of photosensitizers, and its structural conversion was assessed by agarose gel electrophoresis (AGE), transmission electron microscopy (TEM) and capillary gel electrophoresis (CGE). The generation of reactive oxygen species (ROS) from photoirradiated photosensitizers was also assessed by spectrophotometrical determination. Concomitant ultraviolet (UV) exposure of pBR322 DNA and photosensitizers resulted in significant oxidative damage to the DNA, as evidenced by AGE, TEM and CGE data, indicating a structural transition from supercoiled form to open circular form. Photosensitizer-induced DNA damage was attenuated by the addition of radical scavengers, especially sodium azide, a typical scavenger of singlet oxygen (1 O2), and enhanced by the addition of deuterium water, an enhancer of the life time of 1 O2. These data, taken together with the results of the ROS assay, suggest that singlet oxygen might act as a major toxic species in quinine-induced photogenotoxicity. The structural analysis of plasmid DNA by CGE after exposure to UVA/B in the presence of photosensitizers could be automated, allowing easy, fast and highly reliable prediction for the photogenotoxic potential of a large number of drug candidates.

Current malaria status and distribution of drug resistance in East and Southeast Asia with special focus to Thailand.

Malaria is the world's most important parasitic infection ranking among the major health and developmental challenges. Despite years of continual efforts, malaria is still one of the major causes of morbidity and mortality affecting third-world countries and still a threat to over 2 billion people, representing approximately 40% of the world's population in about 100 countries (Rollback Malaria 2005). During the "eradication era", half a century ago, malaria was eliminated or effectively suppressed in many parts of the world, particularly subtropical regions. The disease is now on the rise again since it is appearing in areas where it had disappeared. The disaster can largely be attributed to antimalarial drug resistance in most malaria endemic countries. Geographical distribution of the disease is worldwide, being found in tropical areas, throughout sub-Saharan Africa and to a lesser extent in South Africa, Southeast Asia, the Pacific Islands, India and Central and South America. Best estimates currently describe the annual global burden of malaria as 300-500 million cases and 1-2 million deaths. Over 90% of the disease burden is in sub-Saharan Africa. The malaria burden differs according to age and gender; almost all deaths occur in African children under 5 years of age (Snow et al. 2001). Pregnant women in Africa (especially primigravidae) are at high risk, and are the major adult risk group in the continent. An increasing number of imported cases of malaria have been reported particularly as a result of increasing worldwide travel to regions where there is ongoing risk of malaria transmission. Nowadays, cases of malaria acquired by international travelers from developed countries probably number 25,000 cases per year, with 10,000 of them reported annually and approximately 150 deaths per year.

Quinine lowers serum and testicular testosterone in adult Sprague-Dawley rats.

We have earlier demonstrated that quinine (QU) is a testicular toxicant. This present study was aimed at evaluating the effects of QU on both the serum and testicular levels of testosterone (TT) in an attempt to elucidate one of the potential mechanisms of QU-induced testicular toxicity. Thirty adult male Sprague-Dawley rats weighing 180-200g were used and were randomly divided into 3 groups of 10 rats each. Rats in group 1 had distilled water. Rats in group 2 had QU only at the dose of 10 mg/kg body weight per day (5 days in a week) for 8 weeks. Rats in group 3 rats had 10 mg/kg of QU (5 days in week) and 0.05 mg/kg of TT (3 days in a week) for 8 weeks. All the animals were sacrificed at the end of 8 weeks by decapitation. Seminal analysis was done on the tubular fluid aspirated from the caudal epididymides. The two testes were excised, weighed, and volume estimated. One testis of each rat (0.25 g of tissue) was homogenized with Potassium Chloride and TT level determined in the supernatant of the homogenate, while the other testis was processed for histology. Morphometry was carried out by assessing the diameter, cross-sectional area, number of profiles per unit area, length density and numerical density of the seminiferous tubules, and the relative and absolute volume of testicular components. The serum levels of TT in all the animals were also determined at the time of sacrifice. Both the serum and testicular levels of TT in rats administered QU only were significantly (P < 0.001) lower than those of the control and QU plus TT-treated rats. We conclude that QU induces spermatogenic epithelial toxicity by possibly interfering with the steroidogenic function of the Leydig cell.