Hydrocarbons, C4

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: EU Risk Assessment

Adequacy of study:

other information

Reliability:

other:

Data source

Reference

Reference 1

Reference Type:

other: EU Risk Assessment

Title:

European Union Risk Assessment Report 1,3-BUTADIENE, CAS No: 106-99-0, EINECS No:203-450-8

Author:

[ECB] European Chemicals Bureau

Year:

2002

Reference 2

Reference Type:

publication

Title:

Mortality, morbidity, and haematologic results from a cohort of long-term workers involved in 1,3-butadiene monomer production.

Author:

Cowles, S.R. et al.

Year:

1994

Bibliographic source:

Occup Environ Med. 51; 323-329.

Reference 3

Reference Type:

publication

Title:

A haematological survey of workers at a styrene-butadiene synthetic rubber manufacturing plant.

Author:

Checkoway, H. and Williams, T.M.

Year:

1982

Bibliographic source:

Am Ind Hyg Assoc J. 43; 164-169.

Reference 4

Reference Type:

publication

Title:

Occupational exposures to mists and vapours from strong inorganic acids; and other industrial chemicals.

Author:

IARC monographs on the evaluation of carcinogenic risks to humans.

Year:

1992

Bibliographic source:

IARC monographs on the evaluation of carcinogenic risks to humans. Volume 54. International Agency for Research on Cancer: Lyon, France. pp 137-285.

Reference 5

Reference Type:

publication

Title:

Changes in peripheral blood of workers from certain chemical industries.

Author:

Khristeva, V. and Mirchev, N.

Year:

1981

Bibliographic source:

Khigiena i Zdraveopazvanie Sofia. 24; 436-441 (NTC translation 82 13291-06J).

Reference 6

Reference Type:

review article or handbook

Title:

Occupational exposure limits for airborne toxic substances.

Author:

International Labour Office

Year:

1977

Bibliographic source:

Occupational safety and hygiene series no 37. International Labour Office: Geneva, Switzerland.

Reference 7

Reference Type:

publication

Title:

Occupational exposure to butadiene and some cellular immunity parameters in petrochemical workers.

Author:

Zeman, K. et al.

Year:

1989

Bibliographic source:

Medycyna Pracy. 40; 99- 104 (HSE translation no. 15046A).

Reference 8

Reference Type:

publication

Title:

Assessment of biochemical and clinical indicators of occupational exposure in petrochemical industry employees.

Author:

Tomaszewski, L.

Year:

1987

Bibliographic source:

Medycyna Pracy. 38; 167-174.

Materials and methods

Study type:

cross sectional study

Endpoint addressed:

repeated dose toxicity: inhalation

Principles of method if other than guideline:

EU Risk Assessment on the major component of C4 Hydrocarbons: 1,3-Butadiene

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Buta-1,3-diene

EC Number:

203-450-8

EC Name:

Buta-1,3-diene

Cas Number:

106-99-0

Molecular formula:

C4H6

IUPAC Name:

buta-1,3-diene

Details on test material:

- Name of test material (as cited in study report): 1,3-butadiene
- CAS number: 106-99-0
- EINECS number: 203-450-8

Method

Type of population:

occupational

Ethical approval:

not specified

Details on study design:

EU Risk Assessment on the major component of C4 Hydrocarbons: 1,3-Butadiene
Inhalation studies in humans

Exposure assessment:

measured

Results and discussion

Any other information on results incl. tables

An analysis of morbidity and haematological parameters was included within a mortality study in a cohort of male workers potentially exposed to butadiene at a US butadiene monomer manufacturing facility (Cowles et al., 1994). All male employees with a minimum of 5 years in jobs with potential exposure to butadiene or who had worked at least half of their total employment in jobs with potential exposure (minimum 3 months) were eligible for a study cohort. A total of 614 employees met these criteria and 438 of these were still employed during the period of the morbidity study, 1982-1989. Account was taken of smoking history, blood pressure, cholesterol level and obesity as health risk factors. A morbidity event was defined as a specific diagnostic condition which caused an absence of more than 5 days in the period 1982-1991. Only one morbidity event per employee was counted in any diagnostic category, although if an employee had more than one morbidity event in different diagnostic categories, each was counted. Haematological parameters - red cell count, haemoglobin concentration, mean corpuscular volume, platelet count, white blood cell count, neutrophil count and lymphocyte count - were also measured in 429 of these employees and mean values were adjusted for the effects of age and smoking status. Over 2,600 non-exposed employees at the same plant were used as controls. Exposure data for 1979-1992 indicates that in this period, 8-hour TWA exposures were in the range <0.1 to 143 ppm, with most below 1 ppm and a mean exposure of 3.5 ppm.

There was no evidence of any excess of ill health in the butadiene group compared with controls. Similarly, haematological parameters showed no differences between butadiene workers and controls, including a separate subgroup of workers identified as having the potential for the highest butadiene exposures (8-hour TWA ~ 10 ppm). Overall, this study shows no significant differences in health status or haematology parameters in butadiene- exposed workers compared with non-exposed workers at the same plant. However, it is a limited study in terms of cohort size and lack of exposure data for the period under study.

A haematological survey was performed on all workers at a US styrene-butadiene rubber manufacturing plant (Checkoway and Williams, 1982; IARC, 1992). Air and blood samples were obtained during a single week in 1979. A total of 163 workers participated in the hygiene study, 154 of whom also participated in the blood survey. Blood samples were analysed for red cell

count, haemoglobin concentration, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin concentration, reticulocyte count, platelet count and total and differential white cell count. There were minimal changes in haematological parameters in 8 workers exposed to about 20 ppm butadiene, 14 ppm styrene and 0.03 ppm benzene compared with the majority of workers

exposed to <1.7 ppm butadiene, 2 ppm styrene and 0.1 ppm benzene (8-hour TWAs). These changes are not considered to provide evidence of an effect of exposure to butadiene, because of their minimal nature, the mixed exposures and because other confounding factors such as alcohol consumption were not considered.

Effects on haematological parameters have been noted in workers from the butadiene department of a Bulgarian synthetic rubber plant (Khristeva and Mirchev, 1981). In the plant as a whole, atmospheric levels of butadiene, styrene and ethylbenzene were several times those of the maximum permitted concentrations. However, in the butadiene department, workers were exposed apparently to butadiene alone, presumably to more than 45 ppm (International Labour Office, 1977). The butadiene workers had a statistically significantly increased haemoglobin concentration and reticulocyte count. In addition, prothrombin time was increased and platelet

count and leukocyte peroxidase activity were decreased, all statistically significantly. However, the biological significance of the results is impossible to assess because of the absence of numerical data to support the claim that these workers were exposed to butadiene alone and the lack of information on the control group.

No effect on immune function was apparent in a poorly reported study of workers in the butadiene division of a petrochemical refinery (Zeman et al., 1989). A second poorly reported study in the same group of workers reported an increase in levels of ¿-glutamyltransferase and glycine transamidase compared with local unexposed populations (Tomaszewski et al., 1987).

However, because of a lack of detail and quantitative information, no conclusions can be drawn from this.

The health effects of repeated butadiene exposure has been investigated in workers at synthetic rubber production plants in Russia, in numerous studies (Alberton et al., 1981; Alekperov et al., 1970; Balan and Sergeta, 1973; Bashirov, 1968, 1969a,b, 1970, 1971, 1975; Batkina, 1966; Drogichina et al., 1959; Gus'kova, 1971; Kapkaev, 1963; Kats, 1962; Khusainova, 1971; Klein et al., 1967; Konstantinovskaya, 1970, 1971; Lukoshkina et al., 1973; Mukhametova et al., 1976; Nadirova, 1967; Netesa et al., 1969; Ogleznev, 1980; Putalova, 1979; Ripp, 1967; Sergeta et al., 1975; Vinokurova, 1969, 1970; Volkova and Bagdinov, 1969). However, in all of these reports, co-exposure to a range of other chemicals was noted and the effects seen were not associated

with exposure to any specific chemical. In addition, very limited information was given on exposure levels. Thus the reports are of little value for assessing the health effects of butadiene.

In some of these workers, the incidence of health effects increased in workers with longer service (Abdullaeva, 1973). However, when it was attempted to correlate sickness rates with exposure to individual chemicals, there was no evidence that butadiene exposure was associated with significant adverse health effects (Abdullaeva, 1974).

Applicant's summary and conclusion

Executive summary:

There is little useful information on the health effects in humans of repeated exposure to butadiene.

The results of one modern, well-reported study show no excesses of morbidity nor any changes in haematological parameters in workers at a butadiene production facility, where the mean 8-hour TWA, measured after the period of the study, was 3.5 ppm.

None of the other studies available are of a quality and reliability that permits meaningful conclusions to be drawn.