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Toxicological information

Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
other: retrospective cluster investigation
Adequacy of study:
supporting study
Study period:
1985-2011
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Cholangiocarcimoma among offset colour proof-printing workers exposed to 1,2-dichloropropane and/or dichloromethane.
Author:
Kumagai, S., Kurumatani, N., Arimoto, A., Ichihara, G.
Year:
2013
Bibliographic source:
Occup Environ Med. 70: 508-510 doi:10.1136/oemed-2012-101246

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
carcinogenicity
GLP compliance:
no
Remarks:
not applicable

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
no information available.
used certificates from suppliers obtained over the years.

Method

Type of population:
occupational
Ethical approval:
not specified
Details on study design:
METHOD OF DATA COLLECTION
- Type: Interview of workers / Medical record review of patients

STUDY PERIOD: 1985 - 2011

SETTING: colour proof-printing section of a small printing company in Osaka, Japan.

STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 62 male wrkers
- Selection criteria: exposure to chemicals used in proof-printing


HEALTH EFFECTS STUDIED
- Disease(s): cholangiocarcinoma

Exposure assessment:
estimated
Details on exposure:
TYPE OF EXPOSURE: reproduced working environment

TYPE OF EXPOSURE MEASUREMENT: Air sampling

EXPOSURE LEVELS: estimates of 100 - 670 ppm

EXPOSURE PERIOD: 1985 to 2006

POSTEXPOSURE PERIOD: 2006-2011

Results and discussion

Results:
EXPOSURE
- Range concentration estimate: 100-670 ppm

INCIDENCE / CASES
- Incidence/ Number of cases for each disease: 11 deaths from cholangiocarcinoma among 62 male workers

STATISTICAL RESULTS
- SMR (Standard mortality ratio): 2900, E: 0.00204, 95% CI: 1100-6400
Confounding factors:
- co-exposure with other chemicals, especially methylene chloride
Strengths and weaknesses:
This investigation is methodologically weak with many gaps. Weaknesses:
- worker identification process
- exclusion of female workers
- did not survey all cholangiocarcinoma cases in the company
- did not confirm/investigate pathological characteristics of cholangiocarcinoma cases
- retrospective estimation of exposures to chemicals
- co-exposures with many chemicals

Applicant's summary and conclusion

Conclusions:
The authors of the Japanese worker study conclude that 1,2-dichloropropane and/or dichloromethane "may cause cholangiocarcinoma in humans."
Executive summary:

11 deaths from cholangiocarcinoma were reported among 62 Japanese color proof-printing male workers. The standardized mortality ratio (SMR) was 2900 (95% CI 1100-6400). Cholangiocarcinoma is a relatively rare cancer with an incidence of a 1 to 2 per 100,000 with a mean age of incidence of 66 years. All cases of cholangiocarcinoma in the Japanese workers were among relatively young workers, ages 25-45. This investigation is methodologically weak with many gaps. The workers in this study were exposed to many chemicals including several chlorinated solvents; all of the workers who developed cholangiocarcinoma were exposed to 1,2-dichloropropane and most were also exposed to dichloromethane. The exposures were retrospectively estimated. Female workers were excluded from the analysis. Another study of dichloromethane workers did report an increased risk of biliary tract cancers (SMR=20, 95% CI 5.2-56) [ Lanes, et al., 1990]. The authors of the study conclude that 1,2-dichloropropane and/or dichloromethane “may cause cholangiocarcinoma in humans.” However, the co-exposure with methylene chloride and other chemicals, and the finding in another study of dichloromethane workers of elevated biliary tract cancers would provide some evidence that 1,2-dichloropropane was not the exposure that caused the excess.