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Toxicological information

Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Cohort study for which no guidelines are available, published in peer reviewed literature, limitations in design and reporting, but otherwise adequate for assessment

Data source

Reference
Reference Type:
publication
Title:
An evaluation of chronic methylene chloride exposure
Author:
Soden KJ
Year:
1993
Bibliographic source:
J Occup Med 35 (3), 282-286

Materials and methods

Study type:
cohort study (retrospective)
Endpoint addressed:
repeated dose toxicity: inhalation
Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
See details of study design for the method
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Dichloromethane
EC Number:
200-838-9
EC Name:
Dichloromethane
Cas Number:
75-09-2
Molecular formula:
CH2Cl2
IUPAC Name:
dichloromethane

Method

Details on study design:
Cohort Selection
Two plants were selected as a basis for comparison: a triacetate fibers plant in Rock Hill, South Carolina, and a polyester staple plant in Salisbury, North Carolina. The Hoechst Celanese Corporation (HCC) triacetate production plant used a mixture of solvents (methylene chloride, acetone, and methanol) to produce the fibers and operated this process from 1954 to 1986 at the Rock Hill, South Carolina, site (Celriver).
A group of employees (n = 1271) at this plant had previously been identified as having had relatively high exposure to methylene chloride as part of an epidemiologic mortality study involving employees working in the triacetate production process. Average exposures to methylene chloride in this group were 475 ppm (8-hour time-weighted average), whereas acetone and methanol averaged 900 ppm and 100 ppm, respectively (8-hour time-weighted average).
From this group all of the 150 active employees at the Rock Hill plant as of December 31, 1986 who had worked for at least 10 years in the relatively high methylene chloride exposure area of triacetate production and who also had participated in the HCC health monitoring program (HMP) between 1984 and 1986, were selected.
Employees selected into the control or non-methylene chloride-exposed group were active employees at the Salisbury plant as of December 31, 1986 who worked for at least 10 years at that plant and who also had participated in the HCC HMP between 1984 and 1986 (n = 260). The Salisbury plant was selected as the non-exposed cohort because there are no workplace exposures that have any known effects related to the parameters being studied and the plants are socioeconomically and demo-graphically similar as well as geographically proximate. The Salisbury plant produces polyester staple and industrial grade polyester used in a variety of textile and business applications. There is no methylene chloride exposure at the plant.
For each exposed cohort member, two controls were selected at random, matching for age, sex, and race. As a consequence, the age distribution of both cohorts was proportionally the same and the median ages were also similar.

Exposure Assessment
Exposure assessment for both cohorts was performed routinely as part of the HCC industrial hygiene monitoring program. All monitoring was done using standard, validated in hospital measuring techniques and analysis was done by national certified laboratories. Although the methylene chloride group was exposed to a mixture of solvents, it is felt that the health effects exerted by acetone and methanol would not be deleterious at the levels found in the plant based on toxicological data and commonly accepted permissible exposure levels.
Selection of Study Parameters
HCC had begun an employee HMP in 1981 in its Film and Fibers Group. Both the Celriver (exposed cohort) and Salisbury (non-exposed cohort) plants participated in the HMP and currently have extremely active and successful programs with participation rates greater than 90%. The frequency of the medical examinations is dependent on both age and occupational exposures. Some employees receive annual exams while others receive examinations every 2 to 3 years.
The HCC HMP is a voluntary program, but participation remains high because it is viewed by employees as a positive employee benefit and all medical data are held strictly confidential. No information is released to anyone outside of the medical department without the employee's written permission.

The HCC HMP consists of a health history, laboratory screening and a physical examination. They are:
• Health history questionnaire-the questionnaire contains numerous questions related to past exposures, health symptoms, known medical diagnoses, medications, reproduction, and life-style factors. There is a baseline questionnaire given to all new employees (or new participants in the HMP) and a periodic questionnaire used to update the baseline information.
• Laboratory testing-various medical tests are performed including chest radiography, electrocardiogram, urinalysis, pulmonary function tests, audio-metric exam, and numerous blood tests (chem-26 and complete blood count). All blood-work was performed by Roche Biomedical Laboratories in Burlington, NC.
• Hands-on examination-the final step is a physical examination by a physician or certified nurse practitioner which utilizes all of the above information. If any occupational and/or non-occupational health risks are identified, the employee is counseled appropriately and sent for follow-up.
The following health parameters/questions were selected from the HCC HMP:
• Health History Questions:
"Since your last exam, do you now have or have you had any of the following":
a. chest discomfort with exercise
b, racing, skipping or irregular heartbeat
c. recurring severe headaches
d. numbness/tingling in hands or feet
e. loss of memory
f. dizziness
• Blood Chemistries
a. SGPT (ALT)
b. SGOT (AST)
c. Total bilirubin
d. Hematocrit

Not all employees responded to every health history question so the number reported in the denominator varies slightly. Not all employees included in each cohort had bloodwork done as part of the HCC HMP program during the study period. This occurs because the HMP program is a voluntary age-adjusted program. Therefore, the frequencies of the examinations offered to employees increase with age. The HMP examinations are also not intended to replace or interfere with examinations offered by an employee's private physician. Because employees may have had a recent encounter with their private physician, they often defer part or all of an HMP examination until the next regularly scheduled time period. Likewise, all of the various components of an examination are not offered by every occasion. In one year, an employee may be offered a history questionnaire plus minor measurements, while in the next year all components are examined. Hence, there are fewer numbers of employee values reported than responded on the health history questionnaire. Because the medical examination program was designed to screen for potential adverse health effects from chemical exposures, employees working in chemical exposure areas tend to have a slightly higher participation rate in the examination program.
Exposure assessment:
measured

Results and discussion

Results:
Health History Questions
Responses to the selected health history questions were tabulated from the periodic health history questionnaire (see Table 1). No statistically significant differences were found for the responses between the two groups.


Bloodwork
Both the Celriver and Salisbury populations appear to be similar when comparing the selected hematological parameters. (See Table 2).
The comparison for SGOT was borderline significant at the 0.06 level and is remarkable in that the control group has a higher mean value level than the exposed group. However, this still is not clinically significant.

Any other information on results incl. tables

TABLE 1

Responses to Selected Questions on the Health Monitoring History Questionnaire*

Questions

Exposed(%)

Non-exposed(%)

1. Chest discomfort with exercise

3/149 (2)

10/257 (4.0)

2. Racing, skipping, or irregular heartbeat

8/149 (5.5)

15/252 (6.0)

3. Recurring severe headaches

5/147 (3.5)

14/258 (5.5)

4. Numbness/tingling in hands or feet

15/137 (6.4)

20/247 (8.1)

5. Loss of memory

2/150 (1.3)

1/255 (0.4)

6. Dizziness

4/148 (2.7)

12/255 (4.8)

* Denominators varied slightly because not all employees responded to every health history question.

TABLE 2

(Mean Values) Comparison of Selected Blood Chemistries from Periodic HealthMonitoring* 

 

Exposed (No.)

Non-exposed (No.)

P Value

SGPT(normal= 0 to 50 IU/L)

27.9 (90)

25.6 (120)

0.24

SGOT(normal = 0 to 50IU/L)

25.1 (90)

28.2 (120)

0.06

TOT. BILIRUBIN(normal= 0.1 to1.2mg/L)

0.45 (90)

0.44 (120)

0.44

HEMATOCRIT(normal= 39% to 55%)

44.1 (103)

43.7 (126)

0.22

 * The number of employees varies because no all emplyees underwent every blood test

Applicant's summary and conclusion

Conclusions:
There were no adverse health effects or differences in symptoms reported in employees chronically exposed to a mixture of solvents including relatively high levels of methylene chloride (475 ppm; 1677 mg/m3) when compared to a control group of non-exposed employees for selected cardiac, neurological, and hepatic health parameters in an employee HMP.