Lead tetraacetate

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: Epidemiology-Lead Neurotoxicity-Occupational

Adequacy of study:

key study

Study period:

May 1980-June 1981

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The rationale for the reliability scoring is based upon a Lead Study Quality Assessment tool for Neurological Effects in the Occupational Setting developed by the Scientific Advisory panel assembled to provide independent academic review of the Voluntary Risk Assessment for Lead. The Occupational Assessment assessed study quality on the basis of the following major aspects of study design, data collection and analysis. Adequacy of Cohort Definition and Size Nature and Extent of Lead Exposure Indices Examiner Training and Procedures for Data Collection and Analysis Precision of Endpoint Definition Extent of Correction for Major Confounding Variables

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1984

Materials and methods

Study type:

cohort study (prospective)

Endpoint addressed:

neurotoxicity

Principles of method if other than guideline:

The present paper describes the first year of a three year project. Prospective Cohort Study.

Test material

Test material information

Constituent 1

Reference substance name:

Lead

EC Number:

231-100-4

EC Name:

Lead

Cas Number:

7439-92-1

Method

Type of population:

occupational

Ethical approval:

not applicable

Details on study design:

HYPOTHESIS TESTED (if cohort or case control study): To evaluate the effects of chronic lead exposure on the nervous system in adults.


METHOD OF DATA COLLECTION
- Type: Interview / Questionnaire / Record review / Work history / Clinical tests / other:
- Details: Job Histories and clinical tests.


STUDY PERIOD: May 1980-June 1981


SETTING: Foundry production workers and an assembly plant located adjacent to the foundry.


STUDY POPULATION
- Total population (Total no. of persons in cohort from which the subjects were drawn):
- Selection criteria: 99 lead exposed foundry workers
- Total number of subjects participating in study:
- Sex/age/race:
- Smoker/nonsmoker:
- Total number of subjects at end of study:
- Matching criteria:
- Other:

COMPARISON POPULATION
- Type: State registry / Regional registry / National registry / Control or reference group / Other comparison group:
- Details: 61 unexposed assembly plant workers


HEALTH EFFECTS STUDIED
- Disease(s): Symptom Prevalence, Nerve Conduction
- ICD No.:
- Year of ICD revision:
- Diagnostic procedure:
- Other health effects:


OTHER DESCRIPTIVE INFORMATION ABOUT STUDY: Each individual received a questionnaire, a neuirological examination, neurobehavioral testing, and blood and urine analyses. Most workers also underwent nerve conduction testing.

Exposure assessment:

measured

Details on exposure:

Current and past blood lead concentrations were used to estimate the degree of lead absorption; all previous blood lead concentrations had been less than or equal to 90 ug/100 ml. Blood lead concentrations of the 'unexposed' workers ranged from 10 to 42 ug/100 ml, while the exposed ranged from 13 to 80 ug/100 ml. In view of this overlap the two groups were combined and stratified in subsequent analyses based on measured blood lead concentrations. As a result, the two lowest exposure strata (current blood lead concentration: 0-20 ug/100ml and 21-40 ug/100 ml) contain individuals from both the foundry and the assembly plant. The mean blood lead concentration was 32.8 ug/100ml (10-80).

Statistical methods:

Exposure Characteristics-Using blood test results and employment histories, the time weighted average blood lead concentration over the 12 month period before the testing was calculated (TWA-12 months) as a summary of cumulative past exposure for foundry workers only. The blood lead concentration measured on the day of testing was used to indicate current exposure. Blood lead concentrations of exposed workers during the months before being hired were assumed to equal the mean level for unexposed workers.
Control of confounding-To adjust for the effects of age, sex, and education on neurobehavioural tests, and the effects of age, height, weight, and limb temperature on nerve conduction measurements, multiple linear regression analysis of the data obtained from the unexposed population was used to develop a prediction equation for each test. Predicted values were derived for each individual using these equations, and the ratio of actual to predicted was computed (and multiplied by 100) to give a percent predicted value for each individual's performance on each test.
Evaluation of dose response relationships- To assess the relationship of current blood lead concetration to test performance, individuals were grouped into four exposure categories, according to blood led concentration on the day of testing, and the group means of the percent predicted values for each test were calculated. An exposure group whose performance was comparable to the referent population on a particular test should have an average percent predicted score near 100. In most tests, if lead exposure impairs performance, test scores for those in higher exposure groups average below 100%. The opposite relationship holds for five of the POMS subtests (all except the Vigor scale): in this case large raw scores indicate an adverse effect and, therefore, percent predicted scores increase with excess reporting of symptoms. (Continuation below under "Any other information on materials and methods").

Results and discussion

Results:

Workers with PbB levels between 40-60 ug/dl showed impaired performance on tests of verbal concept formation, visual/motor performance, memory and mood.

Confounding factors:

Age, sex, and education were controlled on neurobehavioral tests. Age, height, weight, and limb temperature were controlled on nerve conduction measurements. Alcohol consumption and carbon monoxide exposure were also investigated. Although these factors may have influenced test performance in some cases, they were not correlated with lead exposure level and, as such, would not distort the results.

Applicant's summary and conclusion

Conclusions:

Workers with blood lead concentrations between 40 and 60 ug/100 ml showed impaired performance on tests of verbal concept formation, visual/motor performance, memory, and mood. Thus impairment in central nervous system function in lead exposed adults occurred in the absence of peripheral nervous system derangement and increased iin severity with increasing lead dose.

Executive summary:

To evaluate the effects of chronic lead exposure on the nervous system in adults, a set of neurobehavioural and electrophysiological tests was administered to 99 lead exposed foundry employees and 61 unexposed workers. Current and past blood lead concentrations were used to estimate the degree of lead absorption; all previous blood lead concentrations had been less than or equal to 90 ug/100ml. Characteristic signs (such as wrist extensor weakness) or symptoms (such as colic) of lead poisoning were not seen. Sensory conduction in the sural nerve was modestly slowed by lead exposure but conduction in the ulnar and peroneal nerves was not affected. By contrast, various neurobehavioral functions deteriorated with increasing lead burden. Workers with blood lead concentrations between 40 and 60 ug/100 ml showed impaired performance on tests of verbal concept formation, visual/motor performance, memory, and mood. Thus impairment in central nervous system function in lead exposed adults occurred in the absence of peripheral nervous system derangement and increased in severity with increasing lead dose.