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

Wright, J. Michael; Schwartz, Joel; Vartiainen, Terttu; Mäki‐Paakkanen, Jorma; Altshul, Larisa; Harrington, Joseph J; Dockery, Douglas W.

doi:10.1289/ehp.02110157

Cited by 54 publications

(49 citation statements)

References 44 publications

(60 reference statements)

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“…TTHM concentration may be of limited value as a surrogate of DBP exposure because the degree of correlation with individual THMs and nonvolatile DBPs can vary dramatically by water system (King et al 2000;Whitaker et al 2003;Wright et al 2002). We observed effects similar in magnitude for individual THMs such as chloroform and BDCM, although most of the water systems in our study had low levels of brominated THMs.…”

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confidence: 49%

“…We previously measured MX and mutagenic activity in Massachusetts' surface water systems described in detail elsewhere (Wright et al 2002). Briefly, we collected 88 tap water samples from 36 towns during the fall and spring of 1997 and 1998.…”

Section: Methodsmentioning

confidence: 99%

“…The relationship between fetal development outcomes and individual nonvolatile DBPs has not been examined, but these DBPs are likely even less correlated with TTHM concentrations (Wright et al 2002). We previously detected high levels of MX and mutagenic activity in drinking water from Massachusetts (Wright et al 2002), as well as associations between TTHM and different fetal development indices (Wright et al 2003). In the present study, we used several years of birth certificate data to examine the relationship between indices of fetal development and various town average exposure metrics.…”

mentioning

confidence: 93%

“…These associations are not likely attributable to HAAs or THMs, because these DBPs are not considered strong mutagens (Daniel et al 1993;Rosenthal 1987). MX was strongly correlated with mutagenic activity (r = 0.86) in drinking water samples from Massachusetts (Wright et al 2002), but adjustment for MX in the regression models did not substantially alter the effect of mutagenic activity on mean birth weight (data not shown). Mutagenicity may be a better indicator of the complex mixture of mutagenic compounds present in drinking water than are traditional DBP surrogates, but additional research is needed to determine the correlation between mutagenicity and individual DBP concentrations.…”

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confidence: 95%

“…Kramer et al (1992) examined the impact of total organic halides but reported difficulty distinguishing between the effects of this surrogate with highly correlated DBPs. The relationship between fetal development outcomes and individual nonvolatile DBPs has not been examined, but these DBPs are likely even less correlated with TTHM concentrations (Wright et al 2002). We previously detected high levels of MX and mutagenic activity in drinking water from Massachusetts (Wright et al 2002), as well as associations between TTHM and different fetal development indices (Wright et al 2003).…”

mentioning

confidence: 99%

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The effect of disinfection by-products and mutagenic activity on birth weight and gestational duration.

Wright

Schwartz

Dockery

2004

Environ Health Perspect

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Epidemiologic studies of disinfection by-products have traditionally focused on total trihalomethane (TTHM) concentration as a surrogate for maternal exposure during pregnancy. We used birth certificate data on 196,000 infants to examine the effect of third-trimester exposures on various indices of fetal development. We examined the effect of town-average concentrations of TTHM and additional exposure metrics in relation to mean birth weight, mean gestational age, small for gestational age (SGA) infancy, and preterm delivery. Trihalomethane data (TTHM, chloroform, and bromodichloromethane) from 1995-1998 were available for 109 towns in Massachusetts. Data from 1997-1998 on haloacetic acid (total haloacetic acids, dichloroacetic acid, and trichloroacetic acid), 3-chloro-4-(dichloromethyl)-5- hydroxy-2(5H)-furanone (MX), and mutagenicity were available for a limited number of towns. We observed reductions in mean birth weight (12-18 g) for maternal trihalomethane exposures > the 90th percentile compared with those < the 50th percentile. Birth weight reductions were detected for chloroform exposures > 20 microg/L and TTHM exposures > 40 microg/L. Elevated trihalomethanes were associated with increases in gestational duration and a reduced risk of preterm delivery. We found evidence of an exposure-response effect of trihalomethanes on risk of SGA, with odds ratios (ORs) ranging from 1.09 to 1.23 for bromodichloromethane exposures > 5 microg/L. Elevated mutagenic activity was associated with SGA [OR = 1.25; 95% confidence interval (CI), 1.04 to 1.51] and mean birth weight (-27 g; 95% CI, -54 to -1). Although smaller in magnitude, our findings are consistent with previous studies reporting associations between trihalomethanes and SGA. These data also suggest a relationship between fetal development indices and mutagenic activity independent of exposure to trihalomethanes, haloacetic acids, and MX.

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confidence: 49%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 93%

mentioning

confidence: 95%

mentioning

confidence: 99%

See 3 more Smart Citations

The effect of disinfection by-products and mutagenic activity on birth weight and gestational duration.

Wright

Schwartz

Dockery

2004

Environ Health Perspect

Self Cite

169

128

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Chlorination By‐products

Wright

Venkatapathy²,

Weintraub

2004

Water Encyclopedia

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Disinfection of drinking water is considered one of the most successful public health interventions, effectively eliminating various waterborne diseases from many parts of the world. Chlorination is used for primary and secondary disinfection of drinking water and remains the predominant disinfectant choice worldwide. A disadvantage of chlorine and other disinfectants is their ability to react with organic and inorganic matter in water to form disinfection by‐products (DBPs). Teratogenic and carcinogenic effects have been detected in toxicological studies of DBPs, and epidemiological studies have also reported associations between DBP exposures and carcinogenic, reproductive, and developmental endpoints. Despite recent analytical improvements, many DBPs remain unidentified. The trihalomethanes are the most studied and regulated DBPs, although drinking water regulations and guidelines have been developed for several other DBPs. Exposure to DBPs can occur through ingestion, inhalation, and dermal contact depending on factors such as volatility and water usage behavior. For example, exposure to the volatile trihalomethanes can occur through all three routes of exposure, while exposure to nonvolatile haloacetic acids is primarily through ingestion. While the potential health effects associated with DBPs remain unclear, individual exposures can be reduced via point‐of‐use treatment (e.g., boiling or filtering water) prior to consumption.

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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

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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.

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

Cited by 54 publications

References 44 publications

The effect of disinfection by-products and mutagenic activity on birth weight and gestational duration.

The effect of disinfection by-products and mutagenic activity on birth weight and gestational duration.

Chlorination By‐products

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

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