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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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
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 (A detailed description of the scoring criteria can be found in the .pdf document attached to the 'Epidemiological Data Scoring Rationale Document' record at the beginning of Section 7.10.2).
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Genital malformations in newborns of female nickel-refinery workers.
Author:
Vaktskjold, A., Talykova, L., Chashchin, V., Nieboer, E., Thomassen, Y., Odland, J.
Year:
2006
Bibliographic source:
Scand J Work Environ Health. 32(1):41- 50.
Reference Type:
publication
Title:
Spontaneous abortions among nickel-exposed female refinery workers.
Author:
Vaktskjold, A., Talykova, L., Chashchin, V., Odland, J., and Nieboer E.
Year:
2008
Bibliographic source:
Intl J Envir Health Research 18(2):99-115.
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.
Reference Type:
publication
Title:
Maternal Nickel Exposure and Congenital Musculoskeletal Defects.
Author:
Vaktskjold, A., Talykova, L., Chashchin, V., Odland, J., and Nieboer E.
Year:
2008
Bibliographic source:
Am.J.Ind. Med. 51:825-833, 2008.

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Oxidic nickel (as cited by Thomassen et al, 1999 - supporting study that examined exposure data for the the Vaktskjold et al studies in this study record. See full citation at the end of this study record). Nickel dihydroxide is an oxidic nickel species.
- Substance type: oxidic nickel

Method

Type of population:
occupational
Ethical approval:
confirmed, but no further information available

Results and discussion

Results:
A. Vaktskjold conducted additional epidemiologic investigations using the pregnancy outcome and exposure databases that had been established. A birth-registry based study was carried out in order to determine whether pregnant women employed in the nickel refinery were at elevated risk of delivering a newborn with genital malformation (Vaktskjoldet al., 2006). No effect of maternal exposure to water-soluble nickel was observed for this outcome. In this paper, a categorical exposure matrix was employed based on the previous exposure assessments conducted.
In 2007 and 2009 Vaktskjoldet al. published three additional manuscripts on the on the results of his further examination of reproductive impairment in nickel workers of the Kola Peninsula region of Russia. These manuscripts examined spontaneous abortions, small-for-gestational-age newborns, and musculosketal effects in newborns of female refinery workers exposed to nickel (Vaktskjoldet al., 2007, 2008a, 2008b). These manuscripts also showed no correlation between nickel exposure and the observed reproductive impairment. In each case the manuscripts conclude that, “The study did not reveal a statistical association between maternal exposure to water-soluble Ni in early pregnancy and the risk of …….”.

Any other information on results incl. tables

Table 1: Inhalable aerosol and urinary concentrations of nickel and cobalt by department.a
(GM = geometric mean, 95% CI = 95% confidence interval, P = primary refining, S = secondary refining)

Department at the Moncĕgorsk Refinery Complex

Water-soluble subfraction of the

inhalable aerosol fraction (µg/m3)

Urinary concentrations
(µg/I)b

Nickel

Cobalt

Nickel

Cobalt

GM

95% CI

GM

95% CI

GM

95% CI

GM

95% CI

 Background 

-

-

-

-

5.9c

4.7-7.0c

-

-

Control, research and technical departments

-

-

-

-

-

-

-

-

Construction, repairs, supply and service departments

-

-

-

-

-

-

-

-

Sulfuric acid production

-

-

-

-

6.3

4.8-84

-

-

Copper electrorefining (S)

14d

12-17d

0.1d

0.1-0.1d

15

12-18

0.59

0.5-0.7

Copper pyrometallurgical (S)

14d

10-18d

0.5d

0.4-0.6d

8.3

6.9-10

0.72

0.6-0.9

Matte converting (P)

24

12-46

0.6

0.3-1.1

20

13-32

0.48

0.3-0.7

Beneficiation (P)

3.0

2.0-5.0

0.1

0.1-0.2

5.1

39-66

0.36

0.3-0.5

Oreroasting (P)

18

14-24

0.6

0.4-0.8

11

8.5-14

0.62

0.5-0.8

Oresmelting (P)

62

42-92

1.9

1.2-3.1

20

16-26

1.0

0.8-12

Matte separation (S)

84

56-120

4.1

2.7-6.1

29

21-41

1.8

1.3-2.6

Anode casting, old (S)

250e

180-350e

-

-

159g

122-208g

5.79

4.4-7.4g

Anode casting, new (S)

150e

90-240e

-

-

131g

92-186g

6.1g

4.6-8.2g

Electrorefinery, old (S)

210e

170-260e

-

-

179g

140-230g

1.6g

1.2-2.1g

Electrorefinery, new (S)

225e

150-350e

-

-

127g

96-169g

1.8g

1.2-2.4g

Matte roasting (S)

330e

230-450e

-

-

87g

71-106g

4.0g

3.1-5.0g

Nickel carbonyl plant (S)

17h

11-26h

0.6

0.4-1.2

47

27-81

0.7

0.5-1.1

a  Data for which no source is given are unpublished; although measured, the inhalable levels of arsenic, cadmium, and lead were minimal in all of the operations surveyed [Thomassenet al.,1999 (5); Thomassenet al., 2004 (6)].

b  Although available, creatinine-normalized urinary concentrations do not substantially reduce the variability.

c  From Odlandet al., (4); survey was conducted in 1993-1994.

d  From Thomassenet al., (6); survey was conducted in 1996.

e  The inhalable aerosol nickel fraction was adjusted by the subfraction of the water-soluble nickel determined in a subset of the workers monitored [Thomassenet al., (5)].

f   On the average, the cobalt air concentrations were 1/50thof the nickel concentrations [Thomassenet al., (5)].

g  From Thomassenet al.,(5).

h  These values do not include exposure to nickel carbonyl gas, which is readily absorbed and highly toxic.

Applicant's summary and conclusion

Conclusions:
Occupational Exposure to nickel compounds in a Russian refinery was not associated with the observed increased incidence of perinatal effects in human infants.
Executive summary:

The results from the investigation of reproductive performance in a nickel refinery in Russia are important since spontaneous abortion in humans would most closely approximate the observation of perinatal lethality associated with nickel exposure in rodents.  Further evidence that nickel exposure is not adversely affecting the reproduction of these women is provided by the lack of a “small-for-gestational-age” finding and also the lack of an association of male genital malformations with nickel exposure. Both of these findings are considered “sentinel” (i.e., sensitive endpoints that are easily produced) effects for reproductive toxicity in humans. 

This study demonstartes that even while a poetntial reproductive hazard has been demonstrated by animal studies from exposure to nickel compounds, the risk of such exposures causing adverse reproductive effects in humans is too small to be determined (if it exists at all) by modern epidemiological assessment. Since this Russian cohort is the highest expsoed cohort of female workers identified in a global search, it is unlikely that future work will be able to improve the outcome of this body of work.