Cytogenic effects in the peripheral lymphocytes and kidney cells of rats exposed to 3-chloro-4-(dichloromethyl)-5-hydroxy-2-(5H)-furanone (MX) orally on three consecutive days

Mäki‐Paakkanen, Jorma; Jansson, Kristian

doi:10.1016/0165-1218(95)90081-0

Cited by 20 publications

(7 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3‐Chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2( 5H )‐furanone (MX) has attained much attention as a potentially hazardous by‐product in chlorinated drinking water because it is a potent bacterial mutagen (Kronberg and Vartiainen, 1988; Smeds et al, 1997), genotoxic in mammalian cells (Jansson et al, 1993; Mäki‐Paakkanen and Jansson, 1995; Sasaki et al, 1997) and carcinogenic in rats (Komulainen et al, 1997). There is some evidence, that MX causes developmental toxicity in vitro.…”

Section: Introductionmentioning

confidence: 99%

Developmental toxicity evaluation of 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone (MX) in Wistar rats

Huuskonen¹,

Venäläinen²,

Komulainen³

2003

Birth Defects Research Pt B

View full text Add to dashboard Cite

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a genotoxic chlorination by-product in drinking water. There is some evidence that it has developmental toxic effects in vitro but its potential to cause developmental effects in vivo is not known. The developmental effects were evaluated in Wistar rats. Rats (22-26 dams per dose group) were administered MX by gavage at the dose levels of 3, 30, or 60 mg/kg in water on gestation days 6-19. Control animals received plain water. Clinical signs, body weight, and food and water consumption were recorded for the dams. On gestation day 20, a cesarean section was performed and the ovaries anduterine contents of the dams were examined and the liver, kidneys, spleen, and thyroid glands weighed. The fetuses of all dose groups were weighed, sexed, and observed for external and skeletal malformations and the fetuses of the two highest dose groups were evaluated for visceral malformations. The highest dose, 60 mg/kg of MX, was slightly toxic to the dams. It decreased the corrected body weight gain of dams by 32% and the water consumption by 16-17%. Kidney and liver weights were slightly increased. MX did not affect the number of implantations nor did it cause any resorptions. The body weights of fetuses were not significantly affected. MX did not cause external malformations or skeletal anomalies. Two fetuses at 60 mg/kg and one fetus at 30 mg/kg had major visceral malformations (persistent truncus arteriosus, diaphragmatic hernia, dilated aorta with a stenosis of pulmonary arteries) and two minor artery abnormalities were observed in those animals. The frequency of unilateral displaced testis was slightly higher (9.2%) in the 60-mg/kg dose group than in controls (1.6%). Since the abnormalities did not form a consistent pattern and occurred most at maternally toxic dose, we conclude that MX can be regarded as non-teratogenic.

show abstract

Section: Introductionmentioning

confidence: 99%

Developmental toxicity evaluation of 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone (MX) in Wistar rats

Huuskonen¹,

Venäläinen²,

Komulainen³

2003

Birth Defects Research Pt B

View full text Add to dashboard Cite

show abstract

“…Chlorohydroxyfuranones (CHFs) constitute a potential class of disinfection by-products that might explain the cancer risk associated with chlorinated drinking water. The compound 3-chloro-4-(dichloromethyl)-5-hydroxy-2-(5H)-furanone (MX) has been shown to be genotoxic in bacteria [see, e.g., Meier et al, 1987;Kronberg and Vartiainen, 1988;Watanabe-Akanuma and Ohta, 1994;DeMarini et al, 1995], in mammalian cells in vitro [Meier et al, 1987;Brunborg et al, 1991;Chang et al, 1991;Jansson et al, 1993;Jansson and Hyttinen, 1994;Mäki-Paakkanen et al, 1994;Matsumura et al, 1994;Nunn and Chipman 1994;Harrington-Brock et al, 1995;Marsteinstredet et al, 1997a;Nunn et al, 1997;Holme et al, 1999;Le Curieux et al, 1999], and in mice or rat Furihata et al, 1992;Jansson et al, 1993;Mäki-Paakkanen and Jansson, 1995;Sasaki et al, 1997]. The concentrations of other CHFs in chlorinated drinking water are, however, the same or even higher than that of MX [Smeds et al, 1997].…”

Section: Introductionmentioning

confidence: 99%

Comparable DNA and chromosome damage in Chinese hamster ovary cells by chlorohydroxyfuranones

Mäki‐Paakkanen¹,

Laaksonen²,

Munter³

et al. 2001

Environ and Mol Mutagen

Self Cite

View full text Add to dashboard Cite

Chlorinated drinking water contains several chlorohydroxyfuranone (CHF) by-products whose contribution to cancer risk is not presently known. 3,4-Dichloro-5-hydroxy-2(5H)-furanone (MCA), 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone (CMCF), and 3- chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF) were studied for the induction of DNA damage, using the alkaline single-cell gel (SCG)/comet assay, and for chromosome damage, using sister-chromatid exchange (SCE) and chromosome aberration (CA) tests, in Chinese hamster ovary (CHO) cells. 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), the known genotoxic chlorination by-product and a rat carcinogen, was used as a reference chemical. The SCG analyses were done using concentrations that caused little or no cytotoxicity compared to that of the concurrent control cultures. In the cytogenetic tests, the CHFs were tested up to maximum cytotoxicity. MX and MCA were the most cytotoxic of the compounds in CHO cells followed by CMCF and MCF. All of the CHFs induced DNA damage, SCEs and CAs (mainly chromatid-type breaks and exchanges) in a concentration-related manner, with the exception that MCA was a weak inducer of SCEs. There were no significant differences between the lowest concentration of MX, MCA, and CMCF to cause DNA damage (SCG assay). Based on comparisons of the slopes of regression lines, MX was somewhat more potent than either MCA or CMCF, and MCF was clearly less potent than the other three compounds in the assay. The order of potency was MX > CMCF > MCA > MCF in inducing SCEs and MX > MCA > CMCF > MCF in inducing CAs. The data show that there are differences in the potency of genotoxicity among the CHFs tested. In many cases, however, the extent of maximum effect observed was comparable between the compounds. The results suggest that besides MX other CHFs should be considered in the evaluation of genotoxic risks associated with the consumption of chlorinated drinking water.

show abstract

“…MX has been shown to be one of the most potent bacterial mutagens tested (16). In addition to bacterial assays, MX is a direct-acting mutagen and genotoxin in vivo (17)(18)(19)(20)(21) and in mammalian cells in vitro (21)(22)(23)(24)(25)(26)(27). MX is a multisite carcinogen in male and female rats (6), with an estimated cancer potency 170 times greater than chloroform and 17 times greater than bromodichloromethane (28).…”

mentioning

confidence: 99%

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and mutagenic activity in Massachusetts drinking water.

Wright

Schwartz

Vartiainen

et al. 2002

Environ Health Perspect

Self Cite

View full text Add to dashboard Cite

There is limited information on the prevalence of the potent mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in U.S. water supplies. We measured MX concentrations and mutagenic activity in tap water samples from 36 surface water systems throughout Massachusetts. We found MX levels much higher (up to 80 ng/L) than previously reported in the United States. We also evaluated the role of water treatment on mutagenic activity and disinfection by-product formation. After adjusting for other covariates, chloramination and filtration were the most important treatment options for reducing mutagenic activity and disinfection by-product formation. Multiple chlorine application (before and after filtration) was associated with increased mutagenicity. Chlorine dose, pH, and total organic carbon were also associated with mutagenicity, MX, and total trihalomethane (TTHM) concentration. Seasonal variation was evident for MX and mutagenic activity, with higher levels occurring in the spring compared to the fall. In contrast, TTHM concentrations were greater in the fall.

show abstract

Cytogenic effects in the peripheral lymphocytes and kidney cells of rats exposed to 3-chloro-4-(dichloromethyl)-5-hydroxy-2-(5H)-furanone (MX) orally on three consecutive days

Cited by 20 publications

References 24 publications

Developmental toxicity evaluation of 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone (MX) in Wistar rats

Developmental toxicity evaluation of 3‐chloro‐4‐(dichloromethyl)‐5‐hydroxy‐2(5H)‐furanone (MX) in Wistar rats

Comparable DNA and chromosome damage in Chinese hamster ovary cells by chlorohydroxyfuranones

3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) and mutagenic activity in Massachusetts drinking water.

Contact Info

Product

Resources

About