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Toxicological information

Epidemiological data

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Administrative data

Endpoint:
epidemiological data
Type of information:
other: epidemiology
Adequacy of study:
key study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Cross sectionaly epidemiology study, well targeted with excellent matching of subjects in comparison groups; however, the number of subjects is small (63).

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1990

Materials and methods

Study type:
cross sectional study
Endpoint addressed:
repeated dose toxicity: inhalation
Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Comparison of selected cyanide worker health parameters with those in a chemical production plant
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Type of population:
occupational
Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
Location was Billingham on Cassel Works. The control group was from a nearby chemical (diphenyl oxide) production plant workers. Workers were monitored in the spring and autumn. Physical health of both groups, including physical examination and measurement of biochemical and haematological parameters, as well as information from health questionnaires, were assessed.
Three analyses were carried out:
1. Comparison of the health of cyanide workers with chemical workers
2. Analysis of health of cyanide workers
3. Longitudinal analysis of cyanide workers within 6 months
Exposure assessment:
measured
Details on exposure:
75 workers were eligible and 63 participated. Workers were studied in the spring and fall of 1986; in April , 63 participated and in September, 51 participated. Fifty workers participated in both health screenings.

Workers in the comparison plant were considered radiation workers since one product produced there, Thoria ®, is an alpha-emitter. All had measured zero or very low radiation levels. Hence they routinely had haematology assessments. Workers gave permission to had additional measurement of thyroxin, Vitamin B12 and cyanide.

The cyanide production workplace was divided into sections where the was wet chemistry and the possibility of generation of hydrogen cyanide, versus dry areas producing the dry cyanide salts. Personal protective clothing included overalls, rubber boots, gloves or gauntlets, eye protection (full face shields, goggles or safety glasses), dust masks and air-fed hoods.
Cyanide levels in the workplace were measured by static monitors programmed to set off an alarm at 10 ppm; Draeger pumps, and personal monitoring capturing hydrogen cyanide and cyanide dusts.
Statistical methods:
Statistical methods used Analysis of Covariance, linear and log transformations as needed. For dose-response relationships, differences between observed and fitted values (residuals) from ANOCA were regressed on three measures of exposure: cumulative exposure, current exposure and years of exposure to cyanide (log transformed).

Results and discussion

Results:
Study participants were well-matched in terms of age, height, weight and years of service. There was a significant difference in cigarette smoking behavior, with 89% of cyanide working classified as smokers. Cyanide levels at the plant ranged from 1-3 ppm, and occasionally to levels higher (up to 6 ppm when the plant exposure controls were malfunctioning). Blood cyanide levels were higher in workers with direct contact with cyanide production, but these levels were extremely low and with no detectable acute clinical significance.
Between Group comparison: There were significant differences in haemoglobin, MCH, MCHC, lymphocytes and initial mean cyanide levels. The level of several parameters including initial cyanide and carboxyhaemoglobin were significantly related to cigarette smoking. Thyroxine, carboxyhaemoglobin, Vit B12 levels and blood pressure were not different between the groups.
There was a highly significant interaction between occupational cyanide exposure and cigarette smoking. The level in a non-smoking cyanide worker did not differ from that of smoker in the chemical manufacturing group.
From April to September, among cyanide workers, blood cyanide levels were higher, likely related to plant exposure problems known to have occurred during this time. There were significant changes in systolic blood pressure, carboxyhaemoglobin, MCH, MCHC, platelets and initial mean cyanide levels. There were also some differences in those who performed shift work, history of ill health, medications taken and number of children in the family.
Confounding factors:
Cigarette smoking was a very significant confounder. Weight gain and shift work among cyanide workers was another.
Strengths and weaknesses:
Weakness is the small number (63 workers total). Strengths include excellent matching of participants in two groups and the comprehensive nature of the assessment: biochemical, haematologic, health history, physical examination, assessment of blood cyanide levels at beginning and end of shift, inclusion of thyroxine and assessment of goiter.

Applicant's summary and conclusion

Conclusions:
Initial (morning, pre-shift) levels of cyanide were significantly related to group and to smoking. Smokers from both groups had initial cyanide levels similar to non-smoking cyanide workers. There were no difference in thyroxine levels between groups, and no workers had goiter. No differences between groups were noted for Vit B12, an important measure since low B12 can result in higher blood cyanide levels. No group differences appeared for carboxyhaemoglobin, but within groups, this parameter was strongly associated with smoking. Haemoglobin, MCH and MCHC were higher in cyanide workers than in chemical workers, but these higher values were within the normal range and are considered a chance finding. Findings of high blood pressure over time in cyanide workers were proposed related in increased body mass. More cyanide workers (25%) complained of weight gain than chemical workers (12%). The overall conclusion is that cyanide workers are as healthy as workers in other chemical manufacturing settings. Occupational exposure to 1-3 ppm cyanide vapour, and to levels higher (up to 6 ppm when the plant exposure controls were malfunctioning) is not associated with acute adverse effects.