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Toxicological information

Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study performed a statistical analysis of the association between the contamination of drinking water with chloroform and other trihalomethanes and intrauterine growth retardation. The methodology and its weaknesses are described and discussed in detail.

Data source

Reference
Reference Type:
publication
Title:
The association of waterborne chloroform with intrauterine growth retardation
Author:
Kramer MD, Lynch CF, Isacson P, Hanson JW
Year:
1992
Bibliographic source:
Epidemiology 3(5), 407-413

Materials and methods

Study type:
case control study (retrospective)
Endpoint addressed:
developmental toxicity / teratogenicity
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Population-based case control analysis on the association of chloroform in drinking water with low birth weight, prematurity, and intrauterine growth retardation applying multiple logistic regression statistics.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
not applicable

Method

Type of population:
general
Ethical approval:
not specified
Details on study design:
HYPOTHESIS TESTED (if cohort or case control study):
The study was conducted to determine whether water supplies containing relatively high levels of chloroform and other trihalomethanes within the state of Iowa are associated with low birth weight, prematurity, or intrauterine growth retardation.

METHOD OF DATA COLLECTION
- Type: statistical analysis of birth certificates and water quality survey data
- Details:


STUDY PERIOD:
January 1, 1989 to June 30, 1990

SETTING:
Iowa towns with 1000 to 5000 inhabitants

STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): no data
- Selection criteria: singleton, live infants exhibiting low birth weight, prematurity, or intrauterine growth retardation born to non-Hispanic white women 19 years of age or older and who were residents of Iowa towns with 1000-5000 inhabitants that derived 100 % of their public drinking water from a single source
- Total number of subjects participating in study: 159 live singleton infants weighing < 2500 g (795 randomly selected control infants weighing > 2500 g), 342 singleton, live infants with gestational ages < 37 weeks (1710 randomly selected control infants with gestational ages > 37 weeks, 187 growth-retarded singleton, live infants (935 randomly selected control infants)
- Sex/age/race: no data/new born/non-Hispanic, white



COMPARISON POPULATION
- Randomly selected healthy infants


HEALTH EFFECTS STUDIED
- Low birth weight, prematurity, intrauterine growth retardation
Exposure assessment:
estimated
Details on exposure:
Exposure status was assigned to infants according to maternal residence in a given municipality at the time of birth. The chloroform levels in drinking water were based on a 1987 municipal water survey which included standardised analyses of finished water samples for four trihalomethanes: chloroform, dichlorobromomethane, dibromochloromethane and bromoform. For chloroform, the exposure levels were categorised as undetectable, low (1-9 microgram/litre) and high (> 10 microgram/litre).
Statistical methods:
Multiple logistic regression was used to estimate odds ratios and their 95 % confidence intervals. The regression model for each outcoe inluded adjustment for maternal age, parity, marital status, education, maternal smoking during pregnancy, and adequacy of prenatal care. Since levels of the four trihalomethanes are often correlated, only one trihalomethane exposure was regressed at a time to avoid multicollinearity.

Results and discussion

Results:
There was an increased risk of intrauterine growth retardation associated with higher concentrations of waterborne chloroform and dichlorobromomethane. The elevated risk associated with chloroform remained even when the analysis was restricted to chlorinated water sources, indicating that chloroform has an association over and above that attributable to chlorination alone.
Strengths and weaknesses:
The major limitation of the study involve the ascertainment and classification of exposures to trihalomethanes, including such issue as the imprecision of using aggregate municipal measures for classifying exposure at the level of the individual, potential misclassification due to residential mobility and the fluctuation of trihalomethane levels. The influence of pesticides, herbicides and nitrates could not be directly controlled because these were not measured in the municipal waer survey.

Any other information on results incl. tables

Table 1: Association of adverse reproductive outcomes with waterborne chloroform exposure.

Low birth weight

Exposure to chloroform (mg/L)

Cases (n=159)

Controls (n=795)

Odds ratio*

95 % confidence interval

> 10

25

110

1.3

0.8-2.2

1-9

73

370

1.1

0.7-1.6

undetectable

61

315

1.0

reference

Prematurity

Exposure to chloroform (mg/L)

Cases (n=342)

Controls (n=1710)

Odds ratio*

95 % confidence interval

> 10

39

202

1.1

0.7-1.6

1-9

63

786

1.1

0.8-1.4

undetectable

140

722

1.0

reference

Intrauterine growth retardation**

Exposure to chloroform (mg/L)

Cases (n=342)

Controls (n=1710)

Odds ratio*

95 % confidence interval

> 10

32

113

1.8

1.1-2.9

1-9

92

446

1.3

0.9-1.8

undetectable

63

376

1.0

reference

* Adjusted for marital status, maternal age, number of previous children, prenatal care, maternal smoking and education; ** Intrauterine growth retardation is defined as being under the 5th percentile of weight for gestational age according to California data on non-Hispanic whites.

Applicant's summary and conclusion

Conclusions:
There was an increased risk of intrauterine growth retardation associated with higher concentrations of waterborne chloroform.
Executive summary:

A population-based case-control analysis of the association of chloroform and other trihalomethanes in drinking water with low birth weight, prematurity and intrauterine growth retardation was performed. The analysis used Iowa birth certificates data from January 1, 1989, to June 30, 1990. The study was restricted to singleton live infants born to non-Hispanic white women 19 years of age or older who were residents of Iowa towns with 1000 -5000 inhabitants that derived 100 % of their public drinking water from a single source. Exposure was classified using data from a 1987 municipal drinking water survey measuring chloroform in a unified manner. Three exposure categories were used: undetectable chloroform, 1 -9 microgram/litre of chloroform, > 10 microgram/litre of chloroform.

159 infants exhibiting birth weights below 2500 g were compared to 795 randomly selected control infants, 342 infants exhibiting prematurity were compared to 1710 randomly selected control infants, and 187 infants with growth retardation were compared to 935 randomly selected control infants. Comparisons showed that there was an increased risk of intrauterine growth retardation associated with higher concentrations of waterborne chloroform and dichlorobromomethane. The elevated risk associated with chloroform remained even when the analysis was restricted to chlorinated water sources, indicating that chloroform has an association over and above that attributable to chlorination alone.