Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Currently viewing:

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines, but sufficient data is available for interpretation of results

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977

Materials and methods

Type of study / information:
A prospective cytogenetic study was conducted in 35 workers occupationally exposed to epichlorohydrin.
Principles of method if other than guideline:
A prospective cytogenetic study was conducted in 35 workers occupationally exposed to epichlorohydrin. Blood samples for cytogenetic analysis were collected before the exposure (to serve as a control) and after the first and second years of epichlorohydrin exposure; the cultivation time was 56-58 hours. Four slides from each worker were prepared and two slides were separately analyzed in two collaborating cytogenetic laboratories. About 50 cells were analyzed on each slide.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Workers were producing epichlorohydrin in a new plant

Method

Ethical approval:
not specified
Details on study design:
Blood samples were taken from a group of 35 workers (23 to 54 years old) in three time intervals. The first samples, used as control, were collected just before work started in a newly opened chemical plant producing ECH. The second sampling from the same persons was done after one years exposure and the third set of samples was received after two years exposure. All workers were generally healthy and were neither irradiated nor treated with other known mutagens, including drugs.
Details on exposure:
The workers were exposed to high doses of ECH, ranging from 0.5 to 5.0 mg/m3. So this dose on average exceeded the occupational maximal acceptable concentration value recommended for ECH in Czechoslovakia.

Results and discussion

Results:
Since results of cytogenetic analyses done separately in two laboratories were not significantly different, they were pooled. The average percentage of aberrant cells found in blood samples collected before the start of ECH production was 1.37. This percentage did not differ from the level of aberrant cells spontaneously occurring in human peripheral lymphocytes as reported in a complex study concerned with the incidence of spontaneous chromosomal aberrations in human populations (Bochkov, N.P. (1972)).

After the first year of exposure to ECH, the average frequency of chromosomal aberrations was 1.91%, this percentage being significantly higher than before the exposure (X2 = 5.0, P =0.025).

After the second year of exposure, the frequency of aberrant cells was 2.69% and was again significantly higher than after the first year of exposure (X2 = 8.0, P = 0.005). The difference between the control level and this percentage was highly significant (X2 = 24.0, P<0.0001).

It was mostly chromatid and chormosomal breaks that made up the increasing number of aberrant cells, while chormatid and chromsomal exchanges appeared to be rare in all types of samples.

The increase of aberrations per 100 cells was also clearly evident as well as the increase of breaks per 100 cells which was even more distinctly expressed than the increase of aberrant cells.
Bochkov, N.P. Spontaneous chromosomal aberrations in human somatic cells. Humangenetik. 16:159-164.

Any other information on results incl. tables

These results confirm the assumption that ECH, at dose levels exceeding the current exposure guideline has a mutagenic effect on chromosomes in the peripheral lymphocytes of persons occupationally exposed to ECH.

Applicant's summary and conclusion

Conclusions:
Positive - An increased incidence of chromatd and chromosomal breaks was observed in workers exposed to levels higher than the exposure guideline.
Executive summary:

A prospective cytogenetic study was conducted in 35 workers occupationally exposed to epichlorohydrin (ECH). Blood samples for cytogenetic analysis were collected before the exposure (to serve as a control) and after the first and second years of ECH exposure; the cultivation time was 56 -58 hours. Four slides from each worker were prepared, coded and two of them separately analyzed in two collaborating cytogenetic laboratories. About 50 cells were analyzed on each slide, giving a total 16,674 scored cells.

The percentage of cells with chromsomal aberrations in blood samples of workers was 1.37 before exposure, 1.91 after the first year and 2.69 after the second year of exposure. The difference between percentages of aberrant cells before and after two years of occupational exposure was highly significant (P<0.0001). There was particularly observed an increase of chromatid and chormosomal breaks after exposure, simultaneously with an increased number of breaks per 100 cells. These results are concordant with previously reported cytogenetic data found in experiments with mammals and human cells in vitro.