Urinary arsenic methylation profile in children exposed to low arsenic levels through drinking water

There is a lack of information on arsenic metabolism in children exposed chronically to low levels of arsenic (<50 µg L^?1). The objective of this study was to determine the methylation profile of urinary arsenic metabolites in children exposed to low-level concentrations of arsenic via their drinking water. A cross-sectional study was undertaken in 50 children from four towns in the Yaqui Valley, Sonora, with total arsenic values of 39.9, 16.8, 7.3, and 5.5 µg L^?1 in their drinking water, respectively. First morning void samples were analyzed for inorganic-As (InAs), mono and dimethyl arsenic (MMA and DMA). The total arsenic excreted in urine ranged from 23.1 to 99.1 µg L^?1 and these levels did not vary by sex. Children with the highest level of total arsenic in their drinking water excreted the highest amount in urine and the length of residence and age also had significant contribution. Children with a lower range of arsenic exposure (16.8–5.5 µg L^?1) had similar amounts of arsenic in urine with values of 23.1, 28.2, and 32.6 µg L^?1, respectively. DMA had the highest proportion in urine (52.1–74.7%), followed by InAs (16.3–34.9%) and MMA (4.4–8.4%). Compared to other reports, these children excreted a low %MMA (6.1%), and children from the towns with the lowest levels of arsenic had the highest %InAs and the lowest %DMA. This variability in arsenic methylation was partially explained by arsenic concentration in drinking water, years of residence and age, and may reflect genetic differences or more contribution from different exposure routes. In conclusion, our results show that at low levels of exposure the children's ability to metabolize InAs did not have a linear association with the levels of arsenic, and overall children from the Yaqui Valley excrete a lower %MMA than expected.     

Identification of urinary metabolites in rats administered the fluorine-containing pyrethroids metofluthrin,profluthrin, and transfluthrin

The major metabolites in urine of rats administered the fluorine-containing pyrethroids transfluthrin, profluthrin, and metofluthrin, which are used widely recently as mosquito repellents or mothproof repellents, were identified to establish biological indexes for evaluating the absorption amounts of these pyrethroids in the general population. A single dose of 300?mg?kg^?1 body weight of each pyrethroid was separately administered intraperitoneally to male Sprague-Dawley rats and urine samples were collected until 24 hours after the administration. The metabolites identified by gas chromatography-mass spectrometry were as follows: 2,3,5,6-tetrafluorobenzyl alcohol, 2,3,5,6-tetrafluorobenzoic acid, and 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (DCCA) for transfluthrin; 4-methyl-2,3,5,6-tetrafluorobenzyl alcohol, 4-methyl-2,3,5,6-tetrafluorobenzoic acid, 4-hydroxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (HOCH₂–FB–Al), and 2,2-dimethyl-3-(1-propenyl)-cyclopropanecarboxylic acid (MCA) for profluthrin; 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol, HOCH₂–FB–Al and MCA for metofluthrin. In addition, several compounds estimated to be metabolites were detected as follows: hydroxylated DCCA and its lactone for transfluthrin; 4-hydroxymethyl-2,3,5,6-tetrafluorobenzoic acid (HOCH₂–FB–Ac), hydroxylated MCA and its lactone for profluthrin; 4-methoxymethyl-2,3,5,6-tetrafluorobenzoic acid, HOCH₂–FB–Ac, hydroxylated MCA, and its lactone for metofluthrin. The pyrethroids administered underwent metabolic reactions such as ester hydrolysis and oxidation, and most of the metabolites were excreted as their conjugates into urine. These findings should be useful as basic data for evaluating the health effects of exposure to pyrethroids for the general population.     

Phytotoxicity and uptake of chlorpyrifos in cabbage

Chinese cabbage, Brassica chinensis L., and cabbage, Brassica oleracea L. var. capitata, are the main daily foliar vegetables of the vast majority of the population of eastern and southern China. Cabbages are also planted and consumed widely in other countries. The insecticide and acaricide chlorpyrifos is registered in many countries. Chlorpyrifos controls a variety of insects in plants and soils, and chlorpyrifos is extensively used in the Chinese market. Food poisoning due to the presence of organophosphorus pesticide residues in vegetables has been reported in China provinces. Plant uptake of pesticide residues in air, water, and soil is a source of pesticide residues in vegetables. Here, phytotoxicity and uptake of chlorpyrifos by Chinese cabbage and cabbage were studied in the laboratory using the batch technique. From 0 to 16 days after chlorpyrifos treatment, vegetables roots, stems, leaves, and culture water samples were collected, and the residues of chlorpyrifos in culture water, plant tissues were analyzed using GC-FPD. The results demonstrate that culture solutions with chlorpyrifos had no significant inhibitory effects on vegetable plant height. However, at 1.0 mg/l, it had significant inhibitory effects on the root length and fresh weight of Chinese cabbage. Then, at 10.0 mg/l, it had only significant inhibitory effects on the root length and fresh weight of cabbage compared to the control treatment. The disappearance rates of chlorpyrifos in solutions were in sequence as: nutrition solution with Chinese cabbage, nutrition solution with cabbage, pond water, nutrition solution. The results showed also that chlorpyrifos can be taken up by roots of Chinese cabbage and cabbage from water and subsequently translocated as a function of time. Uptake dynamics of chlorpyrifos from culture solutions by the two cabbage plants were similar.     

围生期毒死蜱暴露致子代8周雄鼠睾丸组织的氧化损伤

毒死蜱是目前全世界使用和销售量最大的有机磷杀虫剂之一。为探讨围生期毒死蜱暴露致8周雄性子鼠睾丸组织的氧化损伤,选择健康Wistar妊娠母鼠于妊娠期(gestation days,GD)第6天至子鼠出生后(postnatal days,PND)21天通过灌胃染毒0、0.75、1.35和2.70 mg·kg~(-1)剂量的毒死蜱,待雄性子鼠8周龄取左侧睾丸实施组织病理学检查,右侧睾丸用以检测丙二醛(maleic dialdehyde,MDA)的含量和谷胱甘肽S转移酶(glutathione S transferases,GST)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、总超氧化物歧化酶(total superoxide dismutase,T-SOD)的活力。结果表明,与对照组比较,随着染毒剂量的增加子鼠体重和睾丸、附睾脏器系数有下降的趋势(P0.05);而MDA呈升高趋势(P0.05)。各组T-SOD和1.35、2.70 mg·kg~(-1)剂量组GSH-Px活力的下降及2.70 mg·kg~(-1)剂量组GST活力的升高均有统计学意义(P0.05)。睾丸组织病理学检查结果可见2.70mg·kg~(-1)剂量组睾丸组织有明显的损伤,管腔中精液量减少,生精细胞脱落增多。上述研究结果提示母鼠于围生期暴露于毒死蜱,可通过氧化损伤诱导子代雄性大鼠睾丸的毒性作用。     

氧化乐果和毒死蜱混剂对大鼠雄性生殖功能的联合毒性

为探讨有机磷农药混合物对生物生殖毒性的影响,以模式动物Sprague- Dawley (SD)大鼠为实验材料,采用亚慢性染毒动物实验,利用3×3析因实验设计方法研究了常见有机磷农药——氧化乐果和毒死蜱的联合雄性生殖毒性效应及机理。结果表明：氧化乐果和毒死蜱联合染毒60 d后,附睾系数增加,精子数量和精子活力降低,联合作用呈现协同效应(p<0.05);混配农药能降低睾丸标志酶乳酸脱氢酶(LDH)、酸性磷酸酶(ACP)、碱性磷酸酶(AKP)、γ-谷氨酰转移酶(γ-GT)的活力,对LDH、ACP、γ-GT的联合作用表现为协同作用(p<0.05);混配农药能增加睾丸中促卵泡生成激素(FSH)含量,降低睾酮(T)含量,联合作用表现为协同作用(p<0.05)。通过组织病理学观察,氧化乐果和毒死蜱混合物能引起曲细精管的萎缩、畸形精子增多、生精细胞坏死、胞浆溶解和线粒体空泡化;支持细胞数量减少,出现坏死,精子从支持细胞上脱落,基底膜脱落等损伤。氧化乐果和毒死蜱对大鼠的联合生殖毒性为协同效应,混合后有明显的增毒作用;对睾丸标志酶(LDH、ACP、γ-GT)活力及睾丸性激素水平(FSH、T)的协同影响,是产生联合生殖毒性的机理之一。以上结果提示,对氧化乐果和毒死蜱进行环境健康风险评价时应考虑这种协同作用。     

Understanding and addressing the environmental risk of microplastics

Over the past decades, the plastic production has been dramatically increased. Indeed, a category of small plastic particles mainly with the shapes of fragments, fibers, or spheres, called microplastics (particles smaller than 5 mm) and nanoplastics (particles smaller than 1 μm) have attracted particular attention. Because of its wide distribution in the environment and potential adverse effects to animal and human, microplastic pollution has been reported as a serious environment problem receiving increased attention in recent years. As one of the commonly detected emerging contaminants in the environment, recent evidence indicates that the concentration of microplastics show an increasing trend, for the reason that up to 12.7 million metric tons of plastic litter is released into aquatic environment from land-based sources each year. Furthermore, microplastic exposure levels of model organisms in laboratory studies are usually several orders of magnitude higher than those found in environment, and the microplastics exposure conditions are also different with those observed in the environment. Additionally, the detection of microplastics in feces indicates that they can be excreted out of the bodies of animal and human. Hence, great uncertainties might exist in microplastics exposure and health risk assessment based on current studies, which might be exaggerated. Policies reduce microplastic emission sources and hence minimize their environmental risks are determined. To promote the above policies, we must first overcome the technical obstacles of detecting microplastics in various samples.     

Lead distribution in rats following respiratory exposure to lead-contaminated soils

Two preliminary experiments were performed to explore the use of an intratracheal instillation technique as a cost-effective method of determining the biokinetics of lead (Pb) following respiratory exposure to Pb-contaminated soils. A novel intratracheal instillation procedure was refined and used to deliver a defined dose of Pb-contaminated soil or PbAc to the lower respiratory tract of rats. In the first experiment, rats were sacrificed at numerous time intervals post-dosing, and liver, kidney, blood, and bone tissues were collected for Pb analysis. In the second experiment, rats were dosed with Pb-contaminated soil or PbAc via intratracheal instillation or gastric gavage. All rats were sacrificed 96 h after dose administration and tissues were collected for lead analysis. Data from these experiments indicate Pb is well-absorbed following intratracheal instillation of Pb-contaminated soil, and the intratracheal instillation technique could be used as a cost effective method for exploring the biokinetics of Pb in Pb-contaminated soils following respiratory tract exposure.     

Chlorpyrifos induces oxidative stress in rats

This study was carried out in male Wistar rats to determine the potential effects of chlorpyrifos (CHP) on oxidative stress, as was reported for organophosphorus (OP) pesticides. Following an acute, daily 3- or 14-day exposure with CHP at doses of 2.5, 5, or 25 mg kg^?1 data showed significant increases in malondialdehyde levels at both exposure durations and at all doses, except for 2.5 mg kg^?1, in hepatic and aorta, kidney, and plasma samples. The nitrites (NO) showed elevation at 25 mg kg^?1 in aorta, at 3- and 14-day exposure, in hepatic tissue with all doses at 3-day exposure, but not at 14-day with a 5 mg kg^?1 dose. In plasma, increases occurred only at 25 mg kg^?1 at both exposure times, and in kidney at all doses and both exposure durations. Superoxide dismutase (SOD) enzyme activity in the aorta sample was statistically significant at all doses at 3 days and at 14 days, except at 2.5 mg kg^?1; and in hepatic tissue only at 25 mg kg^?1 dose at both durations. In plasma SOD activity was elevated at all doses at 3 days, but at 14 days only at 25 mg kg^?1. Data suggests that oxidative stress may be involved in the effects of CHP on rats.     

Photodegradation of the organophosphorus pesticides chlorpyrifos,fenamiphos and vamidothion in water

The photodegradation of the pesticides chlorpyrifos, fenamiphos and vamidothion in water containing 2–4% methanol was examined. Acetone (5%) was added as photosensitizer in the photolysis of vamidothion. A suntest apparatus equipped with a xenon arc lamp which exhibits a radiation very close to natural sunlight was employed. Analyses were performed by direct injection of the water samples containing the photoproducts into a liquid chromatograph with diode array and thermospray mass spectrometric detection. The major photodegradation products were identified by matching their diode‐array spectra with the corresponding spectra of the authentic standards, their retention times and the spectra obtained using positive and/or negative thermospray mass spectrometry. 3,5,6‐trichloro‐2‐pyridinol, fenamiphos sulfoxide and vamidothion sulfoxide were the major photodegradation products from chlorpyrifos, fenamiphos and vamidothion, respectively.     

不同测试方法评估48%毒死蜱乳油对玉米田施药者的人体暴露风险

本研究选取3种不同暴露环境,分别为玉米株高达到施药者膝盖左右(暴露环境1)、达到施药者腰部左右(暴露环境2)和高于施药者身高(暴露环境3),采用手动背负式喷雾器,在这3种暴露环境中施喷48%毒死蜱乳油(EC,稀释500倍),通过贴片法和全身整体测试法(whole body dosimetry,WBD)分析了施药者农药皮肤暴露量(dermal exposure,DE)。依据试验结果,发现在暴露环境1和2中,2种测试方法的农药潜在皮肤暴露量(potential dermal exposure,PDE)无显著性差异,但在暴露环境3中,2种测试方法的PDE之间存在显著性差异(LSD0.05=57.9);对施药者的主要暴露部位进行分析,发现在暴露环境1和暴露环境2中2种测试方法的暴露部位类似,但在暴露环境3中显示,贴片法为手部,全身测试法为上半身(头、颈、前胸、后背及手臂)。使用全身测试法测定PDE同时测定直接皮肤暴露量(actual dermal exposure,ADE),并利用ADE和PDE计算外穿防护服(运动服)渗透率的结果,3种暴露环境分别为4.69%、5.19%和5.54%,比通常假设的防护服或工作服的10%渗透率小。     

养殖场饲养鸡对苯并[a]芘的摄入、排泄和积累

在北京市郊区一家中等规模养鸡场采集了不同品种和不同生长阶段的饲养鸡的肌肉和内脏样品,并同步采集了鸡蛋、饲料、粪便和大气样品,测定了其中苯并[a]芘的浓度,据此分析了苯并[a]芘在饲养鸡体内的积累、排泄和代谢的动态过程.结果显示,饲养鸡体内各组织苯并[a]芘的湿重浓度在0.024～0.15ng·g-1之间,肌肉中的浓度显著低于其它组织;饲料和粪便中的浓度显著高于体内各组织浓度.饲养鸡体内摄入的苯并[a]芘约60%在体内代谢,约三分之一直接排泄进入粪便,仅有少量残留在体内如表皮、肌肉和其他器官中.肌肉、肝脏和胃中苯并[a]芘浓度和总累积量的动态变化规律不尽相同.北京居民摄食类似鸡肉导致的对苯并[a]芘的暴露量较春、秋、冬季呼吸暴露量低两个量级,与夏季呼吸暴露量相当.     

Scanning electron microscopy study of the gills,scales and erythrocytes of Anabas testudineus upon exposure to chlorpyrifos

The present study was undertaken to assess the toxicity of sublethal concentrations (125, 250, and 375 µg L^?1) of chlorpyrifos on Anabas testudineus for 21 days. The morphological changes on the gills, scales, and erythrocytes of A. testudineus were observed using scanning electron microscopy. Gill alterations included highly active mucous cells, epithelial hyperplasia, and fusion of secondary lamellae. The scales showed damaged lepidonts. Oozed out cytoplasmic content and lobopodial projections were observed in the erythrocytes after exposure to chlorpyrifos.     

Functional and morphological alterations induced by uranyl nitrate in rat submandibular gland

Exposure to uranium (U) is an occupational hazard to workers who continually handle it and an environmental risk to the population at large. Adverse effects of U on different tissues, particularly kidneys, have been reported. The aim of the present study was to investigate whether U might produce damage to the rat submandibular gland (SMG). Uranyl nitrate (UN) was used to evaluate the secretory responses to norepinephrine (NE) or to the parasympathomimetic agent, methacholine (MC), along with some morphological and histological parameters. In addition, the presence of U in saliva was determined by atomic absorption spectrometric techniques. Results indicate that intraperitoneal (i.p.) injection of a single dose of UN (2 or 4 mg kg^?1) induced a functional decrease in the induced secretory responses in the rat SMG, demonstrating for the first time that U interferes with salivary secretion. Moreover, salivary responses to MC as well as to NE were decreased after UN administration, in time- and dose-dependent manner, displaying a higher diminution after 7 days post injection. In agreement with the functional studies, the injection of UN produced morphological alterations of SMG, consisting in a reduction of mean acinar area and a marked vacuolization. Data indicate that UN produced an adverse effect in a dose- and time-dependent manner on SMG function and morphology. Furthermore, it was shown that U was incorporated in saliva and therefore, these findings may contribute to create a useful, noninvasive method to detect the exposure to U.     

European starling nestling response to chlorpyrifos exposure in a corn agroecosystem

European starling (Sturnus vulgaris) nestlings were used as a surrogate to study the effect of chlorpyrifos application to a corn agroecosystem on songbird reproduction. Chlorpyrifos was applied in a T‐band at 1.3 kg AI/ha, and residues were measured in soil, earthworms, ground‐dwelling insects, and diet items collected from the crop of starling nestlings. Chlorpyrifos levels in soil peaked at 34.2 μg/g, 4 days post‐application, and dissipated to trace levels by 64 days post‐application. Concentrations of chlorpyrifos in earthworms and ground‐dwelling insects reached 0.9 and 0.7 ug/g, respectively. Starling nestling diet items included invertebrates from eight orders with chlorpyrifos concentrations ranging from trace levels to 10.6 μg/g in earthworms. Nestling brain and plasma cholinesterase (ChE) activity and body mass measurements were taken at 3, 8, and 13 days post‐hatch (DPH). Adult starling fecundity was also measured. Body mass differences between treatment and reference site nestlings at 3 and 13 DPH were not significant at α = 0.05. However, 8 DPH nestlings from the Treatment Site had a transient reduction in weight (p = 0.03) when compared with 8 DPH reference nestlings. There were no significant differences in brain or plasma ChE activities of 3, 8, or 13 DPH nestlings. Further, multiple measures of fecundity (i.e., clutch size, hatching percentage, and fledging percentage) indicated that chlorpyrifos application did not affect starling nestling survival to fledging, as the values from the Treatment and Reference Site were nearly identical. This screening‐level study suggests that although one age group of starling nestlings from the Treatment Site weighed less than their Reference Site counterparts, a single T‐band application of chlorpyrifos did not impair starling nesting success.     

沙尘暴源区土壤盐碱扬尘对大鼠呼吸系统的免疫损伤

为研究沙尘暴源区土壤盐碱扬尘对大鼠呼吸系统的免疫损伤,采集距北京200多公里的张家口张北地区的安固里诺尔干盐湖(N41.316°,E114.350°)0~5 cm的盐碱表土,过200目(75μm)筛,测试土壤盐碱扬尘中水溶性离子。将32只雄性7周龄Wistar大鼠随机分为4组,即生理盐水对照组、低浓度组(1.5 mg·kg~(-1))、中浓度组(7.5 mg·kg~(-1))、高浓度组(37.5 mg·kg~(-1)),配制颗粒物悬液,采用气管滴注急性染毒方式,24 h后处死动物,检测血常规及血浆和肺泡灌洗液(BALF)的总抗氧化能力(T-AOC)、白介素-6(IL-6)、肿瘤坏死因子(TNF-α)、乳酸脱氢酶(LDH)、转化生长因子(TGF-β1)等氧化炎症因子,并制作肺组织和气管病理切片。结果表明,沙尘暴源区土壤盐碱扬尘中含有大量的SO_4~(2-)、NO_3~-和NH_4~+等离子;土壤盐碱扬尘急性染毒会对大鼠气管和肺组织造成明显的炎症病变,并随着染毒试剂浓度的升高而加重;但对大鼠血常规的影响较小。中、高浓度染毒使血浆中T-AOC显著下降(P0.05);染毒促使血浆TGF-β1分泌显著增加(P0.05),但不存在剂量-效应关系,其他氧化炎症指标分泌无显著变化。中、高浓度组BALF的TGF-β1因子分泌量显著高于生理盐水对照组(P0.05),高浓度组BALF中IL-6含量显著低于生理盐水对照组(P0.05),其他氧化炎症指标分泌无显著变化。这些研究显示土壤盐碱扬尘粒径大小及化学成分可能是造成大鼠氧化炎症差异的原因。     

Consumer safety evaluation after monitoring of endocrine disruptor pesticide residues: a case study of Thessaly,Central Greece

Abstract

A large number of pesticides used in agricultural practice has been characterized or suspected to be Endocrine Disruptors, with dietary intake to be the major route of consumer’s exposure. In the present study the safety to consumer after the consumption of pome fruits and fruiting vegetables originated from the area of Thessaly, Central Greece was assessed. Objective samplings of 110 samples were conducted in local retail markets in an effort to quantify potential residues of targeted pesticides, previously characterized as endocrine disruptors. For the determination of residues, a QuEChERs-based multiresidue method coupled with liquid and gas chromatographic systems was applied and fully validated in accordance with the European Unions’s requirements in apples and tomatoes in three fortification levels. Acceptable results were obtained for all the validation parameters studied and the limit of quantification of 0.01?mg/kg and limit of detection of 0.0033?mg/kg were achieved. Based on the determined results, the most frequently determined pesticide was chlorpyrifos with a maximum concentration of 0.32?mg/kg in tomato samples. Cypermethrin and dimethoate were also determined in tomatoes and aubergines. The EFSA PRIMo rev.3.1 model was applied for all positive samples and acute risk for consumers was confirmed only in the case of determination of chlorpyrifos in tomatoes.     

Imidacloprid residues in fruits,vegetables and water samples from Palestine

The aim of this work was to report on imidacloprid [IUPAC name 1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2-ylideneamine] residues in some vegetables, fruits, and water samples collected from the West Bank, Palestine, in 1998 and 1999. Imidacloprid and its derivatives in the study samples were extracted by methanol/water and oxidized into 6-chloronicotinic acid and subsequently derivatized into 6-chloronicotinic acid trimethylsilyl ester before being determined by GC/MS. Imidacloprid residues were detected in more than half of the analyzed samples. The highest and lowest imidacloprid concentrations were found in eggplant (0.46 mg/kg) and green beans (0.08 mg/kg), respectively. An increase of 11–120% in imidacloprid concentration in the 1999 samples was observed when compared with those of 1998. This may suggest imidacloprid accumulation in the soil and/or increased use by local farmers. The imidacloprid residue concentrations in several crops were found to exceed the CODEX maximum residue limit.     

Alterations in some renal parameters of rats induced by aqueous soil extracts

Soil ingestion can be an important route of exposure to contaminants present in the environment. This study examined the effects of exposure to contaminants in aqueous soil extracts from an industrial urban settlement in renal biochemical parameters of treated rats. Male Wistar rats were gavaged with an aqueous soil extract, from the municipality of Rio Grande, Southern Brazil. After exposure, plasma and urine concentrations and plasma protein were assessed compared to rats treated with aqueous soil from relatively unpolluted site (control soil). There was increase in plasma creatinine and total protein in urine, and a decreased glomerular filtration rate in treated rats compared to control. It is possible that Cd, Cr, As, Cu, Pb, Zn, and Ni analyzed in the soil samples and unidentified components may have provoked the observed changes in renal biochemistry of the exposed rat. This may suggest that exposure to contaminated soils can cause damage to the viscera in mammals and it is of public health importance.     

Potential correlation between perfluorinated acids and liver morphology in East Greenland polar bears (Ursus maritimus)

In this study, residual concentrations of chlorpyrifos (CPF) were determined in feed (40) and fodder (25) samples collected from various locations of Tarai region of Uttarakhand. For extracting residues, liquid–liquid partition followed by alumina column clean up was used and the detection and quantification of residues was undertaken with the help of high-performance liquid chromatography using C18 column and diode array detector at 220?nm. Of the total 40 feed samples analyzed, 7 (17.5%) samples were found positive for CPF with the mean residual concentration of 0.058?µg?g^?1; while out of 25 fodder samples, CPF residues were detected in a single (4%) sample with residual concentration of 0.39?µg?g^?1. However, none of the feed or fodder samples contained CPF residues above the prescribed limit.     

Tertiary-butyl acetate metabolism,toxicity, and human health considerations

Tertiary-butyl acetate (TBAC) (CAS No. 540-88-5) is an organic solvent with a potential for occupational and environmental exposure as a result of its use in industrial coatings, adhesives, inks, and degreasers. The objective of these studies was to extend the toxicological database upon which health hazard and risk assessments of TBAC can be made. The metabolism of TBAC was studied in rats exposed by inhalation for 6?h to concentrations of 100 or 1000?ppm. There was an evidence of partial saturation of TBAC absorption and metabolism at some concentration below 1000?ppm. Approximately 5% of the low dose and 26% of the high dose was expired without change within 12?h, while the retained material was rapidly metabolised and excreted, mostly in the urine, within 24?h. Very little radioactivity remained in the tissues after day 7. The metabolism of TBAC appears to follow two major routes: hydroxylation of the tertiary-butyl moiety to form 2-hydroxymethylisopropyl acetate and ester hydrolysis to form tertiary-butyl alcohol (TBA). A minor route involves oxidation of the acetate moiety. Based on the proportion of metabolites that can clearly be assigned to one or the other major pathway, hydroxylation of the tertiary-butyl moiety prevails at 100?ppm, while hydrolysis of the ester bond predominates at 1000?ppm.

Based on nose-only inhalation exposure of rats to TBAC for 6?h, the LC50 for males and females combined is approximately 4200?ppm. Clinical signs included exaggerated breathing, staggering, tremors, and lethargy approximately 1?h after the exposure, but all surviving rats appeared normal from 24?h until the end of the 14?day observation period. An LC₅₀ was not identified for mice. After exposure of whole body for 6?h to 3000?ppm, the highest concentration tested, all mice were prostrate for most of the exposure time, but there were no deaths.

Groups of five male and five female Sprague-Dawley rats were exposed nose-only to 0, 100, 400, or 1600?ppm TBAC 6?h?day^?1 5 days?wk^?1 for 2?weeks. There were no effects on body weight, feed or water consumption, or necropsy findings. Male rats exposed to 1600?ppm had increased liver weights and hypertrophy of centrilobular hepatocytes. An increased proportion of cortical tubule cells with hyaline droplet accumulation was observed in all treated groups of males. Groups of five male and five female CD-1 mice were exposed whole body to 0, 190, 375, 750, or 1500?ppm TBAC 6?h?day^?1 for 14 consecutive days. There were no effects on body weight, feed consumption, or necropsy findings. Liver weights were increased in female mice at 750 and 1500?ppm. Minimal hypertrophy of centrilobular hepatocytes was found in female mice at 375, 750, and 1500?ppm and in male mice at 1500?ppm TBAC.

TBAC did not induce gene mutations in bacterial tests with strains of S. typhimurium and E. coli. Further, there was no evidence of clastogenic activity from tests either for the induction of chromosomal aberrations in human lymphocytes in vitro in the presence or absence of S9 mix or for the induction of micronuclei in bone marrow cells of rats exposed by inhalation for 6?h to 1600?ppm TBAC.

These results are relevant to human health risk assessment and are discussed in the context of previous studies. The weight of the scientific evidence supports the conclusion that TBAC has lower acute toxicity than previously suggested, that it is rapidly excreted when inhaled, and that neither TBAC nor its TBA metabolite are genotoxic or potential human carcinogens.