Registration Dossier

Administrative data

Endpoint:
epidemiological data
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable study

Data source

Reference
Reference Type:
publication
Title:
Mortalite par le cancer bronchopulmonaire dans une fabrique de pigments a base de chromates de plomb et de zinc
Author:
Haguenoer JM, Dubois G, Frimat P, Cantineau A, Lefrancois H and Furon D
Year:
1981
Bibliographic source:
Institut de Medecine du Travail, Faculte de Medecine - 59045 LILLE CEDEX - FRANCE

Materials and methods

Study type:
cohort study (prospective)
Endpoint addressed:
carcinogenicity
Principles of method if other than guideline:
Brochopulmonar cancer related mortality was evaluated in lead/zinc chromate pigment factory workers
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data

Method

Type of population:
occupational
Ethical approval:
not specified
Details on study design:
HYPOTHESIS TESTED (if cohort or case control study): respiratory tract tumor deaths induced by the test material

METHOD OF DATA COLLECTION
- Type: recensement

STUDY PERIOD: Jan 1, 1958 - December 31 1977

STUDY POPULATION
- Total population (total no. of persons in cohort from which the subjects were drawn): 251 active workers during the study period (working in the factory at least for 6 months, starting before 1978 and still alive in 1958).
- Selection criteria: workers in the factory at least for 6 months, still alive in 1958 and having start the work in the plant before 1978.
- Sex/age/race: man
- Total number of subjects at end of study: 201

COMPARISON POPULATION
- Type: population of the department of North, France
- Details: statistics of the reference population were available (from 1958 to 1977), with the numbers of respiratory tract (non secondary tracheal, bronchial and pulmonar) tumor related, as well as total deaths, each 10 years.

HEALTH EFFECTS STUDIED
- Disease(s): respiratory tract tumor
- Diagnostic procedure: cytology and histology (Biopsy).
Exposure assessment:
not specified

Results and discussion

Results:
EXPOSURE
- Average concentrations: could not be determined due to the changes (ameliorations) occurring progressively in the production.

INCIDENCE / CASES
- Incidence/ Number of cases for each disease / parameter under consideration: 30 (from a total of 50) deaths were attributable to pulmonary tumor (11), infarct (3), vasculocerabral accident (2), cerebral tumor (2), suicide (2), pulmonary acute edema (1), acute respiratory insufficiency (1), pancreatite (1), arterite (1), accident (1), intoxication (1), renal insufficiency (1), liver tumor (1), gastrointestinal tumor (2). The reason for the remaining deaths could not be determined.
Confounding factors:
Zinc chromate was manufactured in the factory in parallel to lead chromate; azo and diazo dyes were additionally produced in the same factory up to 1965. It is therefore impossible to specifically incriminate the test substance.

Any other information on results incl. tables

The observed pulmonar tumors are summarized below:

 Observation #  Year of birth  Exposition period (years)  Latency  Tobacco smoking  Diagnostic  Evolution period  Age at diagnostic
 1  1906  12.5  12.5  +    5 months  56
 2  1907  17.5  17.75  +  ganglion biopsy  11 months  59
 3  1917  14  14.75  +  cytology  6 months  51
 4  1911  17.5  17.5  +  bronchial biopsy  6 months  57
 5  1925  23.5  23.5  former smoker  bronchial biopsy  1 year  44
 6  1925  20.25  20.25  +  bronchial biopsy  4 months  46
 7  1909  14.33  14.75  -  1 month  63
 8  1918  2  15  +    1 year  53
 9  1913  17.5  17.5  +  bronchial biopsy  34 months  58
 10  1929  18.75  18.33  +  bronchial biopsy  2 years  43
 11  1904  13.5  21  +  cytology  1 month  71
 12  1924  21.5  22.5  +  bronchial biopsy  6 months  53
 13  1914  19.33  18.75  +    19 months  62
 14  1936  3  4.5  bronchial biopsy  1 month  42

The incidence of deaths due to pulmonary tumor tripled in the control population during the 20 years of the study (310/13367 in 1958 vs. 797/14044 in 1977). Therefore, the comparison of the exposed group to the control population was made in a per year basis.

Based on the observations obtained from the control population the predicted number of deaths due to pulmonary tumor was 2.38 and was significantly lower than the 11 deaths in the exposed population (relative risk: 4.61). This is particularly important since the predicted 44.54 "normal" deaths (not due to pulmonary tumor or of unknown cause) compared to the actually observed 39 was not significant.

Lead poisoning was generally observed in 5 from 11 pulmonary tumor deaths. The urinary chrome levels were elevated in dried environment workers.

Applicant's summary and conclusion