Dinitrotoluene

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: epidemiological study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reliability as cited in OECD SIDS Dinitrotoluene (isomers mixture) CAS No.: 25321-14-6, 2004.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Cardiovascular mortality among munitions workers exposed to nitroglycerin and dinitrotoluene.

Author:

Stayner, L.T. et al.

Year:

1992

Bibliographic source:

Scand J Work Environ Health 18, 34-43

Reference 2

Reference Type:

publication

Title:

Excess hepatobiliary cancer mortality among munitions workers exposed to dinitrotoluene.

Author:

Stayner, L.T. et al.

Year:

1993

Bibliographic source:

J Occup Med 35, 291-296

Reference 3

Reference Type:

secondary source

Title:

Dinitrotoluene (isomers mixture), CAS No.: 25321-14-6

Author:

OECD SIDS

Year:

2004

Materials and methods

Study type:

cohort study (retrospective)

Principles of method if other than guideline:

Cardiovascular and cancer mortality among workers from a US Army munitions facility were investigated.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dinitrotoluene

EC Number:

246-836-1

EC Name:

Dinitrotoluene

Cas Number:

25321-14-6

Molecular formula:

C7H6N2O4

IUPAC Name:

Reaction mass of 1-methyl-2,4-dinitrobenzene and 2-methyl-1,3-dinitrobenzene

Details on test material:

- Name of test material (as cited in study report): dinitrotoluene (DNT)
- Analytical purity: no data

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

HYPOTHESIS TESTED (if cohort or case control study): if DNT exposure is associated with an increased risk of cardiovascular disease and cancers of the liver and biliary tract


METHOD OF DATA COLLECTION
- Type: Work history / Death certificates


STUDY PERIOD: 01 Jan 1949 - 31 Dec 1982


STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 12425
- Selection criteria: workers who had been employed for at least five months at the facility from 1 Jan 1949 to 21 Jan 1980
- Total number of subjects participating in study: 12425
- Sex/age/race: male, white
- Total number of subjects at end of study: 12061


COMPARISON POPULATION
- Type: National registry (US mortality rates)/ Control or reference group (unexposed workers of the same plant)


HEALTH EFFECTS STUDIED
- Disease(s): Mortality from ischemic heart disease (IHD), cerebrovascular disease, cancer of the liver and biliary tract.
- Diagnostic procedure: Death certificates and hospital records

Exposure assessment:

estimated

Details on exposure:

TYPE OF EXPOSURE: airborne and dermal


EXPOSURE LEVELS: An exposure classification scheme was used which identified workers with probable exposure or workers possibly or not exposed.

Statistical methods:

A modified life-table program was used to compute the expected numbers of deaths by multiplying mortality rates specific for cause, five-year age groups, and five-year calendar groups, by the corresponding person-year distribution of the study population. Standardized mortality ratios (SMR) and standardized rate ratios (SRR) were calculated and the according 95% confidence intervals (CI) were estimated.

Results and discussion

Results:

EXPOSURE
- Other: exposure categories: ever versus never exposed and duration of exposure


FINDINGS


INCIDENCE / CASES
- Number of cases for each disease:
Cerebrovascular disease: 36 deaths in the exposed workers; 70 deaths in the unexposed reference group
IHD: 253 deaths in the exposed workers; 423 deaths in the unexposed reference group
Cancer of the liver, biliary abd gall bladder (ICD 155, 156): 6 deaths in the exposed workers; 4 deaths in the unexposed reference group



STATISTICAL RESULTS
- SMR (Standard mortality ratio): comparison with US general population
SMR for cerebrovascular disease: 0.95; exposed workers
SMR for IHD: 0.98; exposed workers
SMR for hypertension without heart disease: 2.06; exposed workers
SMR for other myocardial degeneration: 1.41; exposed workers
SMR for hypertension with heart disease: 1.59; unexposed reference group
SMR for hypertension without heart disease: 1.17; unexposed reference group
SMR for cancer of the liver, biliary abd gall bladder: 2.67 (CI=0.98-5.83)
SMR for overall cancers: 0.84 (CI=0.70-1.00); exposed workers --> healthy worker effect
- SRR (Standard rate ratio): comparison with unexposed reference group
SRR for cerebrovascular disease: 0.89
SRR for IHD: 0.99
SRR for cancer of the liver, biliary and gall bladder: 3.88 (CI=1.04-14.41)
No 95% confidence intervals are given for the major cardiovascular diseases.

Confounding factors:

other cardiovascular risk factors, e. g. smoking
exposure to other chemicals

Strengths and weaknesses:

Potential confounding by employment status
Misclassification of exposure; lack of quantitative information on exposure

Any other information on results incl. tables

The study failed to detect an association between DNT exposure and an increased risk of mortality of ischemic heart disease and cerebrovascular disease. An excess of hepatobiliary cancer was observed among workers exposed to DNT in this study. Exposure-response relationship between duration of DNT exposure and hepatobiliary cancer mortality could not be demonstrated.