Inhaled tert-Butyl Acetate and its Metabolite tert-Butyl Alcohol Accumulate in the Blood during Exposure

Groth, Georg; Freundt, K. J.

doi:10.1177/096032719401300705

Cited by 19 publications

(8 citation statements)

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“…Deaths from exposures to TBAC below 400 ppm have not been confirmed in four independent studies: (1) Groth and Freundt [17] -no deaths at 440 ppm for 5 h or 900 ppm for 4 h; (2) Stillmeadow [16] -no deaths at 470 ppm; (3) current metabolism study -no deaths at 1000 ppm; (4) current acute inhalation study -no deaths at 1873 ppm. Therefore, we carefully examined the IBT study and found the following problems:…”

Section: Acute and Subacute Toxicity Of Tbacmentioning

confidence: 99%

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

Cruzan

Kirkpatrick

2006

Toxicological & Environmental Chemistry

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Tertiary-butyl acetate (TBAC) 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 LC 50 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 À1 5 days wk À1 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 À1 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 bo...

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Section: Acute and Subacute Toxicity Of Tbacmentioning

confidence: 99%

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

Cruzan

Kirkpatrick

2006

Toxicological & Environmental Chemistry

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“…The metabolism of inhaled TBAc was studied in Sprague-Dawley rats by Groth and Freundt (1994). A continuous 5 h exposure to approximately 440 ppm TBAc (via a tracheal canula) resulted in continuously increasing blood concentrations of TBAc and tert-butanol (TBA), a metabolite of TBAc.…”

Section: Key Studies: Metabolismmentioning

confidence: 99%

“…It has been established that TBAc is metabolized in rats to TBA (Groth and Freundt, 1994). Oral TBA exposure has been demonstrated to induce renal tumors in male rats and thyroid follicular cell tumors in female mice (NTP, 1995).…”

Section: Male Rat Kidney Tumor Datamentioning

confidence: 99%

Acute toxicity and cancer risk assessment values for tert-butyl acetate

Budroe

Brown

Salsmon

et al. 2004

Regulatory Toxicology and Pharmacology

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“…It has excellent solvency for a variety of substances. Therefore, TBAc is mainly used for architectural coatings, industrial cleaning, and as a solvent in paints and lacquers (Groth and Freundt,1994 ; Budroe et al, 2004 ; Yang et al, 2007) . Moreover,TBAc has recently been exempted from the definition of a volatile organic compound (VOC) by both the Air Resources Board (ARB) and the local air pollution control and air quality management agencies.…”

Section: Introductionmentioning

confidence: 99%

LC₅₀ Determination of tert-Butyl Acetate using a Nose Only Inhalation Exposure in Rats

Yang¹,

Lee²,

Kwon³

et al. 2010

Toxicological Research

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tert-Butyl acetate (TBAc) is an organic solvent, which is commonly used in architectural coatings and industrial solvents. It has recently been exempted from the definition of a volatile organic compound (VOC) by the Air Resources Board (ARB) . Since the use of TBAc as a substitute for other VOCs has increased, thus its potential risk in humans has also increased. However, its inhalation toxicity data in the literature are very limited. Hence, inhalation exposure to TBAc was carried out to investigate its toxic effects in this study. Adult male rats were exposed to TBAc for 4 h for 1 day by using a nose-only inhalation exposure chamber (low dose, 2370 mg/m3 (500 ppm) ; high dose, 9482 mg/m3 (2000 ppm) ) . Shamtreated control rats were exposed to clean air in the inhalation chamber for the same period. The animals were killed at 2, 7, and 15 days after exposure. At each time point, body weight measurement, bronchoalveolar lavage fluid (BALF) analysis, histopathological examination, and biochemical assay were performed. No treatment-related abnormal effects were observed in any group according to time course. Based on those findings, the median lethal concentration (LC50) of TBAc was over 9482 mg/m3 in this study. According to the MSDS, the 4 h LC50 for TBAc for rats is over 2230 mg/m3. We suggested that this value is changed and these findings may be applied in the risk assessment of TBAc which could be beneficial in a sub-acute study.

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Inhaled tert-Butyl Acetate and its Metabolite tert-Butyl Alcohol Accumulate in the Blood during Exposure

Cited by 19 publications

References 5 publications

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

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

Acute toxicity and cancer risk assessment values for tert-butyl acetate

LC₅₀ Determination of tert-Butyl Acetate using a Nose Only Inhalation Exposure in Rats

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Inhaled tert-Butyl Acetate and its Metabolite tert-Butyl Alcohol Accumulate in the Blood during Exposure

Cited by 19 publications

References 5 publications

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

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

Acute toxicity and cancer risk assessment values for tert-butyl acetate

LC50 Determination of tert-Butyl Acetate using a Nose Only Inhalation Exposure in Rats

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LC₅₀ Determination of tert-Butyl Acetate using a Nose Only Inhalation Exposure in Rats