Registration Dossier

Diss Factsheets

Toxicological information

Epidemiological data

Currently viewing:

Administrative data

Endpoint:
epidemiological data
Type of information:
other: cohort (retrospective) study in workers
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study used sound methods with regard to the questionnaire building and the statistical evaluation of the questionnaire outcomes. However, the exposure information was taken into account only in a qualitative manner.

Data source

Reference
Reference Type:
publication
Title:
Pregnancy outcome of personnel in Swedish biomedical research laboratories
Author:
Wennborg H, Bodin L, Vainin H, Axelsson G
Year:
2000
Bibliographic source:
JOEM 42, 438-446

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
toxicity to reproduction / fertility
Test guideline
Qualifier:
no guideline followed
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Chloroform
EC Number:
200-663-8
EC Name:
Chloroform
Cas Number:
67-66-3
Molecular formula:
CHCl3
IUPAC Name:
trichloromethane
Details on test material:
Not applicable

Method

Type of population:
occupational
Ethical approval:
not specified
Details on study design:
HYPOTHESIS TESTED (if cohort or case control study):
The rate of spontaneous abortions was higher for women who had ever worked in a laboratory compared to women who had never worked in a laboratory.

METHOD OF DATA COLLECTION
- Type: Questionnaire
- Details: A questionnaire was designed with one part probing the women's reproductive history and health status and another part with specific questions relevant to calculations of time to pregnancy during 1990 to 1994.


STUDY PERIOD:
January 1, 1990 through December 31, 1994

SETTING:
Sweden, women who had worked in universitary research laboratories or non-laboratory departments

STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 1052
- Selection criteria: Women born in 1945 or later who had worked for 1 year or more during 1990 through 1994 in a biomedical research laboratory or non-laboratory department at Karolinska Institutet in Stockholm or at the universities of Gothenburg, Linköping, Lund, Stockholm, Umea, or Uppsala and had given birth to at least one child during that period.
- Total number of subjects participating in study: 763
- Sex/age/race: laboratory group: female/23 to 46 years/no data; non-laboratory group: female/23 to 50 years/no data
- Smoker/nonsmoker: no data
- Total number of subjects at end of study: 697

COMPARISON POPULATION
- Type: 1417 single births registered after 1973 in the Swedish Medical Register

OTHER DESCRIPTIVE INFORMATION ABOUT STUDY:
Exposure assessment:
estimated
Details on exposure:
Exposure was estimated qualitatively on the basis of information about the women's education and profession. Each woman was asked about her work in any laboratory, the period during which it occurred, and the exposure to various agents including chemicals (organic solvents or other), radioactive isotopes, cell techniques, viruses, or bacteria during the months before conception. For solvents, specifically, the periods of use wwere requested with an accuracy margin of one month.
Statistical methods:
Statistical analyses. Analyses were performed with multiple logistic regression models for dichotomous outcomes: spontaneous abortions, SGA, LGA, high birth weight, preterm births, postterm births, and malformations. The effect parameter of the logistic model was an odds ratio. Birth weight as a continuous variable was analysed by multiple linear regression, the effect parameter being a regression coefficient with interpretation as a slope parameter, ie, the effect on the outcome of a unit increase in the explanatory variable.
In the initial analyses, the pregnancies were considered independent of one another. Subsequently, to take into account both possible constitutive biological factors specific for a given woman that might affect all of her pregnancies, as well as the cluster sampling scheme with the woman as the primary unit and her pregnancies as secondary units, refined analytical models were used. This accomplished primarily with mixed models in which a random effect for the woman-factor was introduced. We also used a simpler method to incorporated dependence into the logistic models for spontaneous abortions by adding a factor giving the number of previous miscarriages.
The analyses were performed with the Stata 6.0 software package. Specifically, we used the iis/xtlogit procedure in the analyses of random-effect models and iis/xtreg procedure for continuous outcomes.
Interaction factors were tested and goodness of fit was assessed in logistic models with the Hosmer-Lemeshow statistic. In the linear regression models, we used the R2 statistic and evaluation of log likelihood.

Results and discussion

Results:
For 622 women (856 pregnancies) who had worked during the period 1990 to 1994 the analyses of pregnancies for the women who had worked in laboratories relative to pregnancies for the women who had worked in non-laboratory departments yielded an unadjusted odds ratio for spontaneous abortion of 0.9 with a confidence interval 0.5 to 1.4. Table 1 shows the odds ratios obtained in analyses based on a model containing pregnancy-specific explanatory exposure variables for laboratory work, including certain solvents.

Any other information on results incl. tables

Table 1: Odds ratios obtained in analyses based on model containing pregnancy-specific explanatory exposure variables for laboratory work.

Exposure variable

N

Cases

Odds ratio

95 % confidence interval

Cell techniques

NO

676

56

1.0

--

YES

180

17

1.3

0.6-2.5

Bacteria

NO

695

56

1.0

--

YES

161

17

1.2

0.5-2.9

Radioactive isotopes

NO

566

48

1.0

--

YES

290

25

0.8

0.4-1.6

Specific solvents

CHLOROFORM

NO

770

60

1.0

--

YES

86

13

2.3

0.9-5.9

Phenol

NO

773

63

1.0

--

YES

83

10

0.8

0.3-2.5

Use of other solvents

NO

688

57

1.0

--

YES

168

16

0.9

0.5-1.9

Applicant's summary and conclusion

Conclusions:
The study found a weak association between women working with chloroform in laboratories and spontaneous abortions.
Executive summary:

An analysis of the effect of laboratory vs. non-laboratory work on the incidence of spontaneous abortions (lost of the embryo before gestational week 20) was performed on Swedish women born after 1945, who had worked for at least one year between 1990 and 1994 and given birth to at least one child during the period of 1990 to April 1995. To this end, a cohort of 1052 women was identified and questionnaires were sent to these women. The final analysis was performed on 622 women (856 pregnancies) who had responded to the questionnaire. The study found a slightly increased risk for spontaneous abortions among women working in laboratories with chloroform.

Categories Display