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Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
other: a retrospective mortality study
Adequacy of study:
supporting study
Study period:
1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No data on GLP, the relationship of exposure to cancers of the target organ of 2-nitropropane (the liver) were not analyzed separately.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979

Materials and methods

Study type:
other: retrospective mortality study
Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Type of population:
occupational
Ethical approval:
not specified
Details on study design:
Purpose: A retrospective mortality study was initated to determine if there were any unusual disease mortality patterns among Sterlington, Louisiana workers, either before or after the beinning of production of 2-nitropropane. The study included the 1,815 employees that had worked at the plant since 1946. Each death certificate was coded according to the eighth revision of the International Classification of Diseases. The purpose of the study was to determine if thesere were any unusual cancer or other disease mortality patterns among the workers.

Data: The following information was tabulated for each employee and stored in Computer Data File One: name, social security number, date of birth, military service, gender, ethnic group, date of pre-employment exam, medical history, socioeconomic level, date of hire, date of entry in beginning department, date of termination, reason for termination, date of death (where applicable) and plant location. This information, plus address, personal habits (smoking, drinking), departments worked in, occupation in each department, dates of entry into each department, date of transfer and reason for change were entered and stored in Computer Data File Two.

Like information in Computer Data File Two was compared with Data File One. Error sheets were generated. Corrections were made by referral to the employee's file folder. All errors in this phase were eliminated.

Plant seniority (years of service) for each employee was verified using a data processing program. The individual's department seniority plus lay off time in Data File Two had to equal their plant seniority in Data File One within +/- 0.001 years. Plant seniority was calculated using June 30, 1977 or the data of termination (whichever was applicable), minus the data of hire. All errors in this phase were eliminated.

Using information from Data File Two, personnel roster runs were made for each 6 month period. The runs were developed by listing the beginning population for the period, adding the number of new hires and/or inter-company transferees in, and then subtracting the number of terminations and inter-company transferees out. The number of employees on the personnel roster for the period ending June 30, 1977 was identical to the actual population on that data. Upon completion of the rosters, Data File Two was considered to be the Master File.

Of the 180 deaths that occurred amoung the 1,815 employees, all of the death certificates (or the equivalent in the case of military deaths) were obtained. The causes of death were changed for 33 individuals in which the original code was considered incorrect. The living/dead status of past employees was determined for all but 11 individuals. Seven of these were terminated prior to 1955 and four after 1955.

Work activites of the employees were divided into 3 cohorts: direct exposure to 2-nitropropane (laboratory research, production, derivatives, and warehousing), indirect exposure (machine shop, electric shop, general maintenance, instrument shop, shipping, engineering, maintenance, technical service and process development) and no exposure (all other departments such as plant office and other processes). The number of employees in the respective groups was 372, 366 and 743.

Data were expressed as Standard Mortality Ratios (SMR). The SMR is the mathematical comparison between the observed deaths and expected deaths (derived from US mortality rates). It is calculated as observed deaths/expected deaths x 100.

A computer program estimated person-years of observation by color, sex, five year periods of age and time and applied US mortality rates in similar groupings.

Production of 2-nitropropane began in early 1955. Prior to 1955, there were 334 terminated employees. These employees had no possiblity of exposure to 2-nitropropane. The living/dead status was determined for 327 of these employees (98%).

Four individuals out of the 1,481 employees that were employed as of and/or after January 1, 1955 were not accounted for. These individuals worked in locations about 4 miles from the 2-nitropropane operations and had worked for < = 29 days.

Plant History: The plant manufactured materials other than 2-nitropropane. The period between January, 1946 and December, 1954 was a major growth period. The number of products and lines reached a maximum between 1955 through mid 1959. The number of employees remained fairly steady until around 1967, when it started to decrease due to discontinuation of certain product lines. The number of employees started to increase again after 1974 due to expansion of a material other than 2-nitropropane.

Prior to 1962, workplace 2-nitropropane levels were monitored via an informal subjective threshold evaluation. By 1962, workplace concentrations could be monitored. Periodically, concentrations in excess of the present TLV of 25 ppm were observed. The excursions (580 - 1640 ppm) occurred in the drumming area and coincided with the operators experiencing occassional headaches and symptoms of nausea. None of the symptoms required first aid or medical treatment by a doctor. Corrective measures taken to reduce exposure in drumming eliminated complaints of nausea and headache.

Prior to 1977, there was no formalized monitoring system to detect spills and/or leaks. For the first 6 months of 1977, monitored concentrations were 0.2 to 10 ppm (141/144 samples), 10 to 25 ppm (1/141 samples) and 25 to 100 ppm (2 spill area samples/144 total samples).

Results and discussion

Results:
White males: There were 94 deaths (versus 110.3 expected) in the 1066 white males employed between 1/1/1955 and 7/1/1977. The Standardized Mortility Ratio (SMR) of the employed white males was 85. The authors stated that the lowered mortality is a typical finding in an occupational cohort, since it does not include institutionalized subjects that contribute to general population mortality rates. Out of 13 categories [all cancers, seven types of cancers (digestive, respiratory, genitourinary, lymphatic and hematoietic, other lymphatic, and residual cancer), circulatory diseases, respiratory diseases, digestive diseases, external causes (motor vechile accidents, other accidents) and residual], the only categories that had excess mortality in the employed group were external causes (22 vs. 18.7 expected), motor vechicle accidents (11 vs. 6.9 expected), and other lymphatic (2 vs. 0.8 expected).

Black males: There were 27 deaths (versus 40.6 expected) in the 268 black males employed between 1/1/1955 and 7/1/1977. The Standardized Mortility Ratio (SMR) of the employed black males was 67. The only significant finding (p < 0.05) was an increase in other lymphatic cancers in the employed males (2 vs. 0.2 expected). One of these deaths was attributed to mycosis fungoides and the other to "bleeding gastric ulcer-lymphosarcoma". The authors stated that is was unlikely that these two diseases are etiologically related.

Females: There were 8 deaths (versus 2.9 expected) in the 147 females employed between 1/1/1955 and 7/1/1977. The Standardized Mortility Ratio (SMR) of the females was 276. All causes of death examined were significantly higher than expected. Four cancer deaths occurred (versus 0.8 expected). One subject each reportedly died from buccal, respiratory, breast and residual cancers. Two subjects died from external causes and one each died from circulatory disease and "residual". Since the numbers of individuals dying from each cause were small, they did not appear to be related to employment.

Degree of Exposure (direct, indirect or none): There were no differences in the causes of death between individuals grouped according to degree of exposure to 2-nitropropane.

There were 7 deaths due to sarcomatous cancer (a relatively uncommon form). The tumors occurred in different sites and were therefore assigned to different categories. None of these deaths occurred among either directly or indirectly exposed workers.

Years of exposure: There were no clear trends between years of direct or indirect exposure to 2-nitropropane and the numbers of deaths. Among workers with more than 20 years latency (years between beginning of exposure and year of last follow up) there were 9 deaths (vs. 6.4 expected). If this same group was restricted those with more than 20 year's latency and 5 or more years of employment, there were 8 observed deaths and 5.1 expected. There was no suggestion of an excess of any particular cause of death in these individuals. Four of the eight deaths were due to cardiovascular disease and two to malignancy (unspecified primary site, lung cancer).

Person-years accumulated prior to 1955: There were no significant differences between expected and observed deaths in the 711 white males, 146 black males and 103 females who started working prior to 1/1/1955. There were no scarcomatous tumors in this group and the mortality of females was not elevated (in contrast to the post-1954 cohort).

Relationship to county of residence: Most of the employees lived in either Ouachita or Union Counties. The overall cancer rate in Ouachita county was similar to that of Louisiana and the whole United States, and the overall cancer rate in Union County was lower. Relative to the whole United States, residents of both counties had slightly lower age-adjusted rates of cancers of the GI tract. Relative to the United States and Louisiana, residents of both counties had slightly higher age-adjusted rates of skin cancer. Relative to the United States and Louisiana, residents of Ouachita County had slightly higher age-adjusted rates of leukemia and prostate cancer. None of the differences were sufficient enough to suggest a relationship between county of residence and occurrence of particular cancers.


Any other information on results incl. tables

The authors did not mention the excess of other lymphatic cancer in white males to be a significant finding (2 vs. 0.8 expected).  However, they did mention it as being a significant finding in black males (2 vs. 0.2 expected).

It is interesting to note that cancer of the liver was not broken out as a category in this study, since this is the type of cancer that occurs in rats exposed to 2-nitropropane.

Applicant's summary and conclusion

Conclusions:
The authors concluded that there were no unusual cancer or other disease mortality pattern among the workers (either before of after the beginning of 2-mitropropane production in 1955). However, since the cohort was small and the period of latency was short for most of the subjects, the study did not prove that 2-nitropropane was not carcinogenic in humans. The authors recommended that the cohort should be followed and data should be analyzed periodically.