Registration Dossier

Administrative data

Endpoint:
epidemiological data
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: deficiencies in study design and uncertainties in the analysis and reporting of results

Data source

Reference
Reference Type:
publication
Title:
Parkinson's disease in diphenyl-exposed workers--a causal association?
Author:
Wastensson, G., S. Hagberg, E. Andersson, B. Johnels, and L. Barregard.
Year:
2006
Bibliographic source:
Parkinsonism Relat Disord no. 12 (1):29-34. doi: 10.1016/j.parkreldis.2005.06.010.

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
other: neurological
Test guideline
Qualifier:
no guideline required
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

Method

Type of population:
occupational
Ethical approval:
not specified
Details on study design:
METHOD OF DATA COLLECTION
- Type: Record review / Work history / Clinical tests

STUDY PERIOD: study initiated from a cluster of 3 PD cases in 2000 and cohort identified in 2002 out of 506 workers employed in production of biphenyl impregnated paper between 1954 to 1970.

SETTING:

STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 255 living workers living in Sweden in 2002.
- Selection criteria: cohort out of 284 living production workers identified in August 2002 based on the Swedish National Population registry records
- Sex/age: men and women / 50 to <80
- Smoker/nonsmoker: no data
- Matching criteria: no data


HEALTH EFFECTS STUDIED
- Disease(s): Parkinson's disease (PD)
- Diagnostic procedure: at least two of the classical signs (tremor, rigidity, hypokinesia) and a positive reduction in signs with levodopa treatment

Exposure assessment:
estimated
Details on exposure:
estimated exposure levels were more than double the TLV in air set in 1968 (1.3 mg/m3). Some workers may have been exposed to higher peak levels.

Results and discussion

Results:
INCIDENCE / CASES
- Incidence/ Number of cases for each disease / parameter under consideration: 5 PD cases in males identified in cohort of 255 examined workers.

STATISTICAL RESULTS
- RR (Relative risk): 5.6 (95% CI 1.8–13), P=0.002

OTHER OBSERVATIONS:
The long latency period (time from first exposure to onset of symptoms) was 27 to 33 years with the age of onset at 44 to 55 and mean of 51 years.
In the group of 222 deceased workers, nine cases of PD were found, compared to 4.3 cases of PD (RR 2.1, 95% CI 0.96–4.0) expected from data on the lifetime risk of developing PD in the general population.
Strengths and weaknesses:
The design and reported of the study are weak.
Number of workers omitted in analysis and worker missing records that may bias the expected number.
There was a 17 year gap from date of employment to the case ascertainment.
It is unclear why the cohort was selected from 1954 to 1970.

Any other information on results incl. tables

A specialist in occupational medicine examined the cases. Medical records were collected from the neurological departments of local hospitals. A neurologist at the Institute of Clinical Neuroscience at the University Hospital also examined the cases and files for a second opinion. Only cases with at least two of the classical signs (tremor, rigidity, hypokinesia) and a positive reduction in signs with levodopa treatment were included. Cases with atypical neurological signs or treatment with neuroleptic drugs were excluded.

Applicant's summary and conclusion

Conclusions:
The report by Wastensson et al. (2006) has identified a cluster of 5 cases of PD in male employees who worked at some time from 1954 to 1970. Cohort was chosen from group of living individuals less than 80 years of age in 2002. The design and reported of the study are weak. Furthermore, if the cases were related to diphenyl exposure, the levels were likely higher than permitted today, making a similar cluster very unlikely. This observation may be a random occurrence.
Executive summary:

The report by Wastensson et al. (2006) has identified a cluster of 5 cases of PD in living male mill worker employees from Sweden who worked there at some time from 1954 to 1970. These cases were found in a group of 255 biphenyl-exposed workers still living in 2002 that were < 80 years of age and with screened job titles. Deceased workers were not considered in the interpretation and analysis. There may have been more workers in this facility that were not included. Overall, these omissions may have biased the expected PD incidence case umbers. The number of expected cases in the exposed group was estimated by authors to be 0.9, resulting in a reported relative risk of 5.6 (95% CI 1.8–13). Exposure to biphenyl may have contributed to this PD cluster, but chance was given as an alternative explanation by the authors.