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Diss Factsheets

Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
genetic toxicity in vivo, other
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Biological effect monitoring in industrial workers following incidental exposure to high concentrations of ethylene oxide.
Author:
Tates, A.D., Boogaard, P.J., Darroudi, F., Natarajan, A.T., Caubo, M.E., van Sittert, N.J.
Year:
1995
Bibliographic source:
Mutation Research 329, 63 - 77

Materials and methods

GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Ethylene oxide
EC Number:
200-849-9
EC Name:
Ethylene oxide
Cas Number:
75-21-8
Molecular formula:
C2H4O
IUPAC Name:
oxirane
Specific details on test material used for the study:
- Physical appearance: gas

Test animals

Species:
other: human
Strain:
not specified
Sex:
not specified

Administration / exposure

Route of administration:
inhalation
Details on exposure:
Peripheral blood from four groups of seven workers from a chemical manufacturing plant in The Netherlands was analyzed for hemoglobin adducts in erythrocytes and for hprt mutants, micronuclei and SCEs in lymphocytes. Group I workers were incidentally exposed to acute high doses of ethylene oxide ranging from 52 to 785 mg/m3. Group II and III workers were chronically exposed to low doses of ethylene oxide for < 5 years or > 15 years respectively. Group IV workers served as unexposed controls and came from the Occupational Health Department.

Results and discussion

Test results
Remarks on result:
other: This finding implies that the incidental exposure or workers to high concentrations of EtO did not cause any measurable permanent mutational/cytogenetic damage in lymphocytes.
Additional information on results:
Hemoglobin adduct levels in group I workers were very high and ranged from 1461 to 19913 pmol HOEtVal/g Hb approximately 1 month after the accident. HOEtVal values for group II and III workers fluctuated between 0 and 190 pmol/g Hb corresponding with average EtO exposure levels in the range of < 0.01 and 0.06 mg/m3 EtO.
The statistical analysis of the genetic data did not reveal any statistically significant differences between any combination of worker groups. The genetic tests for group I workers were performed on blood samples collected 89-180 days after the incidental exposure. The absence of enhanced frequencies of mutations, micronuclei and SCEs suggests that significant induction of hprt mutations in vivo did not occur and that persistent preclastogenic lesions were not present in significant amounts when the exposed lymphocytes were put in culture to visualize any induced cytogenetic damage. This finding implies that the incidental exposure to high concentrations of EtO did not cause any measurable permanent mutational/cytogenetic damage in lymphocytes.

Applicant's summary and conclusion

Conclusions:
In summary, the present study on hemoglobin adducts in erythrocytes and on hprt mutants, sister-chromatid exchanges and micronuclei in lymphocytes has indicated that acute occupational exposure to high concentrations of the test substance or chronic exposures to low doses of the test substance did not lead to a measurable permanent cytogenetic or mutational damage.
Executive summary:

Peripheral blood from four groups of seven workers from a chemical manufacturing plant in The Netherlands was analyzed for hemoglobin adducts in erythrocytes and for hpti mutants, micronuclei and SCEs in lymphocytes. Group I workers were incidentally exposed to acute high doses of ethylene oxide ranging from 52 to 785 mg/m3. Group II and III workers were chronically exposed to low doses of the test substance for < 5 years or > 15 years respectively. Group IV workers served as unexposed controls and came from the Occupational Health Department. Hemoglobin adduct levels in group I workers were very high and ranged from 1461 to 19913 pmol HOEtVal/g Hb approximately 1 month after the accident. HOEtVal values for group II and III workers fluctuated between 0 and 190 pmol/g Hb corresponding with average test substance exposure levels in the range of < 0.01 and 0.06 mg/m3 of the test substance.

The statistical analysis of the genetic data did not reveal any statistically significant differences between any combination of worker groups. The genetic tests for group I workers were performed on blood samples collected 89-180 days after the incidental exposure. The absence of enhanced frequencies of mutations, micronuclei and SCEs suggests that significant induction of hprf mutations in vivo did not occur and that persistent preclastogenic lesions were not present in significant amounts when the exposed lymphocytes were put in culture to visualize any induced cytogenetic damage. This finding implies that the incidental exposure to high concentrations of the test substance did not cause any measurable permanent mutational/cytogenetic damage in exposed lymphocytes.