Benzoyl chloride

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study is inconclusive on the specific impact of benzoyl chloride on workers since the chemical plant investigated produces many chlorinated compounds. Besides, some bias in the study design are reported. However, the study is generally well described and conducted with accepted scientific principles. This study should therefore be considered as valid with restrictions.

Materials and methods

Study type:

cohort study (retrospective)

Endpoint addressed:

carcinogenicity

Principles of method if other than guideline:

Mortality rates were investigated among British workers exposed to benzotrichloride (98077), benzal-chloride (98873), benzyl-chloride, (100447), and benzoyl-chloride (98884) at a factory that manufactured chlorinated toluenes. The study population included 163 exposed and 790 unexposed factory workers employed for at least 6 months between 1961 and 1970. Death certificates were reviewed for the 91 subjects known to have died. Standardized Mortality Ratios (SMRs) were calculated using the mortality rates of the general population of England and Wales as comparison. A second analysis was performed using the Regression Models in Life Tables technique. 

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Benzoyl chloride

EC Number:

202-710-8

EC Name:

Benzoyl chloride

Cas Number:

98-88-4

Molecular formula:

C7H5ClO

IUPAC Name:

benzoyl chloride

Details on test material:

No data

Method

Details on study design:

HYPOTHESIS TESTED (if cohort or case control study):
- In the standardized mortality ratio approach: The mortality of the study population after adjustments for age and calendar year is similar to the rates of mortality for England and Wales as a whole.
- in the regression models in life-tables approach: null hypothesis is a no effect from exposed people upon cause-specific mortality.


METHOD OF DATA COLLECTION
- Type: Record review was provided by the company investigated presenting contact details of former employees. Mortality rates for the investigated population was checked at the office of population, censures and surveys
No further details


STUDY PERIOD: Between 1961 and 1976 (included).


SETTING:


STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn): 953
- Selection criteria: people working in the chemical plant for at least 6 months at the beginning of the study
- Sex/age/race: male workers aged at least 24
No further data


COMPARISON POPULATION
- Type: Control or reference group assessed to be not exposed to chlorinated compounds
No further data


HEALTH EFFECTS STUDIED
- Disease(s): cancers
- Other health effects: mortality
No further data

Exposure assessment:

estimated

Results and discussion

Results:

STATISTICAL RESULTS
- SMR (Standard mortality ratio): For all causes and for causes other than cancer, SMRs tended to increase with time since first employment. Elevated SMRs were found among the exposed group for all causes, all cancers, digestive system cancers, and respiratory system cancers. The unexposed group had elevated SMRs for cancers of the buccal cavity and throat. For both groups of workers combined, SMRs were increased for all causes and all cancers
- Other:
 Using the Life Tables, cancer mortality was increased only in exposed workers who had first been employed before 1951.
No further data

Confounding factors:

Exposure and observation periods overlap may be subject to artefacts such as the 'survivor population effect'. Smoking status of some people included in the experiment was not known.

Strengths and weaknesses:

Categorization of the whole population included in this experiment was done in two times, it may have introduce a bias. Besides, the size of investigated cohorts is a bit small for statistical significance.

Applicant's summary and conclusion

Conclusions:

In this mortality cohort study, the authors estimated that there is evidence of an increased mortality from cancer but no increase in mortality from other causes amongst the exposed group of a chemical plant producing the intermediate benzoyl chloride.

Executive summary:

Mortality rates were investigated among British workers exposed to benzotrichloride (98077), benzal-chloride (98873), benzyl-chloride (100447), and benzoyl-chloride (98884) at a factory that manufactured chlorinated toluenes. 

The study population included 163 exposed and 790 unexposed factory workers employed for at least 6 months between 1961 and 1970. Death certificates were reviewed for the 91 subjects known to have died. Standardized Mortality Ratios (SMRs) were calculated using the mortality rates of the general population of England and Wales as comparison. A second analysis was performed using the Regression Models in Life Tables technique. 

For all causes and for causes other than cancer, SMRs tended to increase with time since first employment. Elevated SMRs were found among the exposed group for all causes, allcancers, digestive system cancers, and respiratory system cancers. The unexposed group had elevated SMRs for cancers of the buccal cavity and throat. For both groups of workers combined, SMRs were increased for all causes and all cancers. 

In the survival analysis using the Cox Proportional Hazards model, adjusting for age at entry to the survey and the time period when employment began, a statistically significant association between estimated cumulative exposure and deaths from cancer at all sites (but neither digestive nor respiratory cancers individually), was found for persons first employed before 1951.

The authors conclude that exposed workers employed before 1951 have an increased risk of cancer of the respiratory and digestive systems. Based on previous studies, they suggest that the most likely carcinogen is benzotrichoride.

As the authors mention it, cohort population design may have been unappropriate and introduce some bias in the experiment, furthermore the size of the cohorts has little statistical meaning. Besides, characterization of the exposure may have also introduce a bias as both categories (CT- and CT+) were subjective. Finally, no real measurement on exposure to benzoyl chloride is done and no specific results on it are available. Altogether, these parameters raise uncertainties on the conclusion of the impact of benzoyl chloride on workers. However, it gives little evidence and raises concerns on benzoyl chloride impacts on workers. The study is well documented and based on generally accepted scientific principles.

Therefore, considering all these elements, this study should be considered as valid with restrictions.