Trichloroethylene: Effects on body and organ weights in mice, rats and gerbils

Kjellstrand, Per; Kanje, Martin; Månsson, Lennart; Bjerkemo, M; Mortensen, Ida; Lanke, Jan; Holmquist, Björn

doi:10.1016/0300-483x(81)90121-9

Cited by 26 publications

(9 citation statements)

References 7 publications

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“…CNS toxicity in animals is characterized by ataxia, lethargy, hindlimb paralysis, and convulsions; irreversible CNS lesions with accompanying behavioral changes have been induced in several species by chronic exposure to TCE (Kjellstrand, 1980(Kjellstrand, , 1981a. Arito and coworkers (1993) reported abnormal electroencephalogram activity, incapacitation of postural maintenance, decreased waking time, lowered heart rate, and increased numbers of bradyarrhythmic episodes in electrode-implanted and freely moving rats exposed to 3,000 and 6,000 ppm TCE.…”

mentioning

confidence: 99%

Trichloroethylene — a Review of the Literature From a Health Effects Perspective

Gist

Burg

1995

Toxicol Ind Health

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This report reviews the literature on the impact of exposure to trichloroethylene (TCE) on human health. Special emphasis is given to the health effects reported in excess of national norms by participants in the TCE Subregistry of the Volatile Organic Compounds Registry of the National Exposure Registries--persons with documented exposure to TCE through drinking and use of contaminated water. The health effects reported in excess by some or all of the sex and age groups studied were speech and hearing impairments, effects of stroke, liver problems, anemia and other blood disorders, diabetes, kidney disease, urinary tract disorders, and skin rashes.

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confidence: 99%

Trichloroethylene — a Review of the Literature From a Health Effects Perspective

Gist

Burg

1995

Toxicol Ind Health

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“…We have previously studied different effects of TCE exposure in mice Kjellstrand et al 1981Kjellstrand et al & 1983. The effects of PCE exposure were basically the same: increased plasma BuChE activity, increased liver weight and decreased body weight gain.…”

Section: Discussionmentioning

confidence: 99%

“…We have found that liver weight and plasma butyrylcholinesterase (BuChE, EC 3. 1.1.8) are sensitive and reliable measures of different biological effects of TCE in mice ; Kjellstrand et al 1981Kjellstrand et al & 1983. In male mice, BuChE activity increases after TCE exposure, whereas liver weight increase in both sexes.…”

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confidence: 99%

Perchloroethylene: Effects on Body and Organ Weights and Plasma Butyrylcholinesterase Activity in Mice

Kjellstrand

Holmquist²,

Kanje³

et al. 1984

Acta Pharmacologica et Toxicologica

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The effects of continuous and intcrmittent inhalation of perchloroethylene (PCE) on plasma butyrylcholinesterase (BuChE) activity, organ weights, liver morphology and motor activity in mice (strain NMRI) were tested. PCE exposure increased plasma BuChE activity in a time-and concentration dependent manner in both sexes. The increase was statistically significant at 37 p.p.m. in animals continuously exposed for 30 days. BuChE increased approximately 1.5 times in females and 2.5 times in males after 120 days exposure to 150 p.p.m. After rehabilitation of animals exposed for 30 days to IS0 p.p.m., BuChE levels returned to normal. Liver weight also increased in a time and concentration dependent manner. Both sexes exhibited significant liver enlargement at 9 p.p.m. The increase was about 2.3 in females and 1.9 in males after continuous exposure to 150 p p m . for 120 days. After rehabilitation (120 days) of animals exposed to 150 p.p.m. for 30 days, a 10% increase still remained. A decrease in body weight gain was seen in both sexes after exposure to concentrations above 75 p.p.m. Female kidney weight was slightly increased. No clear effect on spleen weight could be detected. When the same time-weighted average conccntration was uscd, intermittent exposure for 30 days had similar effects on livcr weight and BuChE activity as continuous exposure, even when exposures lasted for only one hour per day. Liver cell morphology was changed after PCE exposure. The alterations could be observed already at 9 p.p.m. but disappeared after rehabilitation.

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“…No gross pathological liver effects were observable in several species (rats, guinea pigs, rabbits, dogs) exposed to 730 ppm (8 hr/day, 5 days/week, for 6 weeks) (87). Dose-related (37-300 ppm) increases in LW/BW in mice were reported without more direct measures of liver toxicity (89)(90)(91)(92) Quantitative Dose-Response Analysis Each study previously identified as a potential critical study was evaluated using one or more methods for developing toxicity values (6,1 1). These methods ranged from the default approach used in the absence of any information except a LOAEL to approaches that incorporate mode-of-action and dosimetry data to assist in extrapolating between exposure regimens, dose levels, study durations, and species.…”

Section: Selection Ofinhalation Studiesmentioning

confidence: 96%

Evaluating noncancer effects of trichloroethylene: dosimetry, mode of action, and risk assessment.

Barton

Clewell

2000

Environ Health Perspect

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Alternatives for developing chronic exposure limits for noncancer effects of trichloroethylene (TCE) were evaluated. These alternatives were organized within a framework for dose-response assessment-exposure:dosimetry (pharmacokinetics):mode of action (pharmacodynamics):response. This framework provides a consistent structure within which to make scientific judgments about available information, its interpretation, and use. These judgments occur in the selection of critical studies, internal dose metrics, pharmacokinetic models, approaches for interspecies extrapolation of pharmacodynamics, and uncertainty factors. Potentially limiting end points included developmental eye malformations, liver effects, immunotoxicity, and kidney toxicity from oral exposure and neurological, liver, and kidney effects by inhalation. Each end point was evaluated quantitatively using several methods. Default analyses used the traditional no-observed adverse effect level divided by uncertainty factors and the benchmark dose divided by uncertainty factors methods. Subsequently, mode-of-action and pharmacokinetic information were incorporated. Internal dose metrics were estimated using a physiologically based pharmacokinetic (PBPK) model for TCE and its major metabolites. This approach was notably useful with neurological and kidney toxicities. The human PBPK model provided estimates of human exposure doses for the internal dose metrics. Pharmacodynamic data or default assumptions were used for interspecies extrapolation. For liver and neurological effects, humans appear no more sensitive than rodents when internal dose metrics were considered. Therefore, the interspecies uncertainty factor was reduced, illustrating that uncertainty factors are a semiquantitative approach fitting into the organizational framework. Incorporation of pharmacokinetics and pharmacodynamics can result in values that differ significantly from those obtained with the default methods. Key words: benchmark dose, chloral, developmental toxicity, dose-response assessment, kidney toxicity, liver toxicity, neurotoxicity, PBPK modeling, A consistent framework has been evolving for analyzing dose-response information that reflects relevant biological processes (6,7). Depending on the availability of information, different methods can be used within the overall exposure-dosimetry modeof-action response framework (Figure 1). All dose-response assessment methods begin with the identification of a toxic effect and then estimate acceptable exposure levels protective of human health (7-10). The default approach, in the absence of information, identifies a no-observed adverse effect level (NOAEL) or lowest-observed effect level (LOAEL) and then makes assumptions about mode of action and dosimetry embodied in standard uncertainty factors and adjustments to continuous or daily exposure (11)(12)(13)(14). An This article is part of the monograph on Trichloroethylene Toxicity.

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Trichloroethylene: Effects on body and organ weights in mice, rats and gerbils

Cited by 26 publications

References 7 publications

Trichloroethylene — a Review of the Literature From a Health Effects Perspective

Trichloroethylene — a Review of the Literature From a Health Effects Perspective

Perchloroethylene: Effects on Body and Organ Weights and Plasma Butyrylcholinesterase Activity in Mice

Evaluating noncancer effects of trichloroethylene: dosimetry, mode of action, and risk assessment.

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