Registration Dossier

Administrative data

Endpoint:
health surveillance data
Type of information:
other: Observational
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Human workplace investigation, published in peer reviewed literature, minor restrictions in design and/or reporting but otherwise adequate for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
A hematology surveillance study of petrochemical workers exposed to 1,3 butadiene.
Author:
Tsai SP, Ahmed FS, Ransdell JD, Wendt JK, Donnelly RP.
Year:
2005
Bibliographic source:
J Occup Environ Hyg. 2, 508-515

Materials and methods

Study type:
biological effect monitoring
Endpoint addressed:
repeated dose toxicity: inhalation
Principles of method if other than guideline:
The objective of the study was to evaluate haematological parameters in workers at two 1,3-butadiene plants who had participated in the Shell Butadiene Medical Surveillance Program throughout their working career. The haematology parameters were compared between the two facilities and with a group of employees who had not participated in the program.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
1,3-Butadiene as produced at the Shell Deer Park Manufacturing Complex (Houston, Texas) and the Norco Manufacturing Complex (New Orleans, LA)

Method

Type of population:
occupational
Ethical approval:
not specified
Details on study design:
Entrance criteria to the Butadiene Medical Surveillance Program was open to employees at both plants who were already hired in 1997 or were hired after 1997. There were 3 over-lapping groups:
1. Employees who were potentially exposed to 1,3-butadiene at or above 0.5 ppm TWA-8 (8h time weighted average) for 30 or more days/year.
2. Employees who were potentially exposed to 1,3-butadiene at or above 1.0 ppm TWA-8 during 10 or more days/year.
3. Employees who were potentially exposed to 1,3-butadiene at or above 5.0 ppm over 15 min during 10 or more days/ year.
Additionally, active employees hired prior to 1997 were eligible if they were exposed to 10 ppm of butadiene 30 or more times a year and were still employed by Shell in 1997. Any employee with documented 1,3-butadiene-related disease was also eligible for the program. The comparison group consisted of male and female Shell employees who were not eligible for either the Butadiene Medical Surveillance Program or the Benzene Medical Surveillance Program and were identified from other Shell surveillance programs eg asbestos, lead etc. Employees in the programs had Complete Blood Counts (CBC) taken before entering the surveillance program and at intervals during employment. Individual personal monitoring data was collected from Jan 1 1979 to Dec 31 2003 on workers in 1,3-butadiene production and handling areas. Short term (15 min) and 8-12h TWA data were collected so that “peak” exposures could be determined. The monitoring data was separated into groups – data collected before 1996 when the OSHA (Occupational Safety and Health Administration) exposure limit for TWA-8 was 1000 ppm and post-1996 when it was 1 ppm.
Six hematological endpoints were studied: white blood cell (WBC) count, lymphocyte count, red blood cell (RBC) count, hemoglobin (Hgb) concentration, mean corpuscular volume (MCV), and platelet count.
Analyses used the most recent CBC data for employees who met the following criteria:
1. The employee had to have had at least 2 CBCs performed.
2. The employee had to have had a normal first exam for the cell type analysed.

Results and discussion

Results:
A total of 404 employees were identified from Butadiene Medical Surveillance Program participants across both sites (394 males and 10 females). Mean ages and duration of employment were: males 47.9 yrs and 22.2 years respectively; females 45.7 yrs and 19.3 years respectively. The comparison group contained a total of 773 employees across both sites (750 males and 23 females). Mean ages and duration of employment were: males 49.6 yrs and 23.6 years respectively; females 43.7 yrs and 12.6 years respectively.
The percentage of abnormal values for the six hematological parameters between the butadiene group and the comparison group did not differ significantly for the total population. Overall, 96- 99% of the values for both exposed and comparison groups were within normal ranges. Considered separately, 95-99% of both exposed and comparison groups from Deer Park and Norco were within normal ranges. Overall, the percentage of WBC abnormalities was higher among employees in the 1,3-butadiene surveillance group than those in the comparison group, although the difference was not statistically significant. WBC abnormalities were lower in the surveillance group than those in the comparison group for Deer Park alone but the difference was not statistically significant. Analysis of the 2 sites separately showed no statistically significant differences between the 1,3-butadiene surveillance group and the comparison group for any of the haematological parameters. In the total combined population the only effect was a statistically significant decrease in mean haemoglobin (Hgb) in the 1,3-butadiene surveillance group compared with the comparison group although the difference was very small (14.31 g/100ml vs. 14.44g/100ml) and is probably of no clinical significance. The difference was not statistically significant, however, after adjustment for multiple comparisons using Bonferroni's method.
The exposure data showed that the 1,3-butadiene surveillance group for 1979-1996 had a mean overall exposure of 4.55 ppm (10.07 mg/m3) (8h, 10h and 12h-TWA), from 1997; this figure was 0.25 ppm (0.55 mg/m3). Both facilities gave similar results.

Any other information on results incl. tables

Haematology data for the 1,3-butadiene surveillance group and the comparison group for both plants combined.

 

Exposed

Comparison

P-value

White blood cells (103/mm3)

6.5 (351)

6.60 (658)

0.35

Lymphocytes (103/mm3)

2.04 (360)

2.03 (673)

0.95

Red blood cells (103/mm3)

4.74 (370)

4.75 (676)

0.59

Hgb (g/100 ml)

14.31 (370)

14.44 (688)

0.04*

Mean corpuscular volume (mm3)

90.20 (356)

90.57 (667)

0.17

Platelet count (103/mm3)

248.64 (227)

247.90 (563)

0.84

Values are means (N)

Note: Means adjusted for age, race, sex, smoking status, first exam value, and duration between first and last exams.

*Not significantly different at p < 0.05, adjusted for multiple comparisons using the Bonferroni method.

Applicant's summary and conclusion

Conclusions:
There was no evidence of adverse haematological findings associated with exposure to 1,3-butadiene when workers from 2 plants were compared with a non-1,3-butadiene exposed group.
Executive summary:

Haematological parameters were compared in workers at two 1,3-butadiene plants who had participated in the Shell Butadiene Medical Surveillance Program from 1979 -2003 with a group of employees who had not participated in the program and therefore were not exposed to 1,3-butadiene. Exposure data showed that the 1,3-butadiene surveillance group for 1979-1996 had a mean overall exposure of 4.55 ppm (10.07 mg/m3) (8h, 10h and 12h-TWA); from 1997, this figure was 0.25 ppm (0.55 mg/m3). Before 1996 the OSHA exposure limit was 1000 ppm and post-1996 it was 1 ppm. Both facilities gave similar exposure results. There were no significant differences in 6 Complete Blood Count parameters (white blood cell count, lymphocyte count, red blood cell count, hemoglobin concentration, mean corpuscular volume, and platelet count) between the 1,3-butadiene surveillance group compared with the comparison group when compared on an individual plant basis or all results combined. There was therefore no evidence of adverse haematological findings associated with exposure to 1,3-butadiene.