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Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment. Relevant exposure to submission substance, adequate information on study cohort and exposure, relevant endpoint.

Data source

Reference
Reference Type:
publication
Title:
Small-for-gestational age newborns of female refinery workers exposed to nickel.
Author:
Vaktskjold, A., Talykova, L., Chashchin, V., Odland, J., and Nieboer E.
Year:
2007
Bibliographic source:
Intl J Occ Med Envir Health. 20(4):327- 338.

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
developmental toxicity / teratogenicity
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
No standard guideline reported. Study details provided in the following sections.
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Nickel Metal
IUPAC Name:
Nickel Metal
Details on test material:
- Name of test material: Metallic Nickel from a Nickel refinery
- Substance type: water-soluble, sulfidic, oxidic and metallic nickel

Method

Type of population:
occupational
Ethical approval:
confirmed, but no further information available
Details on study design:
Study population: pregnant women employed in nickel-exposed work areas
Reference group: pregnant women from the same town
Hypotheses tested: The aim in the present investigation was to assess whether pregnancy to elevated levels of water-soluble Ni at the Mončegorsk Ni refinery complex were at a higher risk of delivering an SGA newborn than those not so exposed, in the borough (Moncegorsk). An SGA infant is usually defined as a neonate with a birth weight lower than the 10th percentile for gestational age. In other words, the SGA fetus has not reached its expected size.

Acquisition of data from the Kola Birth Registry. The Registry includes extensive data about more than 98% of all live births, as well as stillbirths of at least 28 weeks of gestation, by residents of Moncegorsk giving birth in the period March 1973 through 2001. The registry included also information about maternal occupation and workplace during pregnancy, compiled from the clinical records. The registered gestational age was obtained from the delivery records. Quantitative air and urine measurements of nickel and other metals and metalloids taken during the observation period (1996–2001) have been used to characterize exposure. The procedures in the factory had remained materially unchanged since 1973, provide assurance that this exposure also reflects past exposures. In total the study population consisted of 22836 newborns.
Exposure assessment:
estimated
Details on exposure:
Quantitative air and urine measurements of nickel and other metals and metalloids taken during the observation period (1996–2001) have been used to characterize exposure. The procedures in the factory had remained materially unchanged since 1973 and provide assurance that this exposure also reflects past exposures.
Statistical methods:
A multiple logistic regression analysis was conducted, with the presence or absence of SGA as the dichotomous outcome. The association between the categories of exposure to water-soluble Ni and the pregnancy outcome was adjusted for factors that were selected a priori based on literature reports of consistent relevant associations and availability of data from the KBR. The following were selected: first delivery (yes/no); regular maternal exposure to solvents at work (yes/no); maternal age > 34 years (yes/no) [21]; maternal height; smoking (yes/no); previous induced abortions (yes/no); and obvious signs of alcohol abuse in pregnancy (yes/no). Considering the potential for residual confounding, an analysis was also run without smoking in the model. Before the onset of the study, we also decided to adjust for the presence of one or more genital defects in a sub-analysis of boys only. Preterm (28–36 weeks) SGA vs. preterm non-SGA newborns were subject to a separate sub-analysis (including also sex as a covariate). In post-hoc sub-analyses, only the newborns of women employed at the Ni refinery complex (see Table 3) were considered, and in another one, those of employed women only.The level of significance was set at 5%.

Results and discussion

Results:
There were 2096 (9.2%) newborns defined as SGA, of these 47.7% were girls The unadjusted odds ratio (OR) of an SGA birth per unit increase in exposure category was 0.79 (95% CI: 0.68–0.91) and the adjusted OR was 0.84 (0.75–0.93) A plausible explanation for the low odds ratio found in the study is a healthy-worker effect. Interestingly, the highest proportion of SGA births was observed among the women who were unemployed or homemakers (11.8%).

Applicant's summary and conclusion

Conclusions:
From the study it can be concluded that there was no adverse effect of maternal occupational exposure to water-soluble Ni in the first part of pregnancy on the risk of delivering a chromosomally normal SGA newborn. However, the finding does not exclude a possibility that exposure throughout pregnancy might produce such an effect.
Executive summary:

Authors' abstract

It has not yet been established whether exposure to nickel (Ni) compounds may cause reproductive toxicity. The objective of this study was to investigate whether women employed under conditions of nickel exposure in early pregnancy were at elevated risk of delivering a newborn small-for-gestational-age (SGA).

A register-based study of a well defined population. Data on pregnancy outcome and maternal occupation were obtained from the Kola Birth Registry. Each birth record was assigned a Ni exposure rating category according to maternal occupation at the time of becoming pregnant. Nickel exposure assessment was based on determining the water-soluble Ni subfraction of respirable aerosol fraction obtained by personal monitoring, and/or on measurements of urine Ni concentration. The reference population were the delivering women with background exposure level. The study population consisted of 22 836 births (> 27 weeks of gestation) and the SGA infants were defined as below the 10th percentile birth weight for gestational age in the source population. Multiple logistic regression was used to analyze the association of the outcome with the assigned exposure rating category.

The adjusted odds ratio for Ni-exposed women for giving birth to an SGA newborn was 0.84 (95% CI: 0.75–0.93).

We found no adverse effect of maternal occupational exposure to water-soluble Ni in the first part of pregnancy on the risk of delivering an SGA newborn without trisomy. The finding does not exclude a possibility that exposure throughout pregnancy might produce such an effect.

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