Reaction products of 2-(chloromethyl)oxirane and glycerol

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well-documented publication, which meets basic scientific principles

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

The Toxicology of Epoxy Resins

Author:

Hine, C.H., Kodama, J.K., Anderson, H.H., Simonson, D.W., Wellington, J.S.

Year:

1958

Bibliographic source:

AMA archive s of industrial health / American Medical Association, 17, p. 129-144

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The effect of multiple dermal application of EPON 562 was studied in Albino rabbits. Acetone was used as a negative control solution. The test material was applied to the backs of rabbits and held in contact for 1 or 7 hours. Applications were made daily (5 days/week) for a total of 20 days. Body weights were recorded weekly; macroscopic and microscopic examinations were performed to determine the systemic effects.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Polyglycidyl Ether of Substituted Glycerin (EPON 562)

IUPAC Name:

Polyglycidyl Ether of Substituted Glycerin (EPON 562)

Details on test material:

- Name of test material (as cited in study report): EPON 562

Test animals

Species:

rabbit

Strain:

other: Albino

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.0 to 3.2 kg

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

acetone

Details on exposure:

These tests were set up according to the Latin square method: four to five spots on each animal's back were depilated, and a different compound applied to each. The compounds were diluted with acetone if it was not practical to apply them undiluted, and the amounts applied were adjusted to give approximately the same final quantity of each compound. The materials remained on the skin for both one-hour and seven-hour periods, in most cases, after which they were removed with acetone. Readings were made just prior to application. The degree of irritation was scored by the same method as for single applications, in which the maximum score for erythema and edema is 8. Applications were made daily except week ends for a total of 20, or until death or eschar formation made further application impractical.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

1 or 7 hours during 8 or 20 days

Frequency of treatment:

once daily

Doses / concentrations

Remarks:

Doses / Concentrations:
no data
Basis:

No. of animals per sex per dose:

No data

Control animals:

not specified

Examinations

Observations and examinations performed and frequency:

The rabbits were weighed weekly.

Sacrifice and pathology:

After the final application, representative animals were killed to determine the systemic effects. Suitable tissues were taken for histologic study.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

dyspnea, rales, nasal discharge

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

maximum degrre of irritation

Mortality:

mortality observed, treatment-related

Description (incidence):

dyspnea, rales, nasal discharge

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

signs of bronchopneumonia

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Effect levels

Dose descriptor:

NOAEL

Remarks:

qualitative assessment of systemic toxicity made

Based on:

test mat.

Sex:

male

Basis for effect level:

other: mortality; clinical signs, body weight; gross pathology; histopathology; irritation effects

Remarks on result:

not determinable

Remarks:

no NOAEL identified

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Polyglycidyl ether of substituted glycerine (EPON 562) produced deaths and clinical signs in animals treated dermally during 8 or 20 days. According to the authors, local effects (severe irritation) prevail over systemic effects.

Executive summary:

The effect of multiple dermal application of EPON 562 was studied in Albino rabbits (Hine et al., 1958). Acetone was used as a negative control solution. These tests were set up according to the Latin square method: four to five spots on each animal's back were depilated, and a different compound applied to each. The compounds was diluted with acetone if it was not practical to apply them undiluted, and the amounts applied were adjusted to give approximately the same final quantity of each compound. The materials remained on the skin for both one-hour and seven-hour periods, in most cases, after which they were removed with acetone. Readings were made just prior to application. The degree of irritation was scored directly after the test material removal. The irritation reactions were scored according to the method of Draize (the maximum score for erythema and edema is 8). Applications were made daily except week ends for a total of 20 days, or until death or eschar formation made further application impractical. The rabbits were weighed weekly, and after the final application, representative animals were killed to determine the systemic effects. Suitable tissues were taken for histologic study. Repeated application of EPON 562 caused definite signs of skin irritation. The applications which were left in place for seven hours did not produce a significantly greater score than the one-hour applications. Final mean scores with EPON 562 approached the maximum degree of irritation (7.6). In the group of animals that were exposed during 8 day to the test material, two of the four treated animlas died six days after the eighth (last) application. These animals showed dyspnea, rales, and nasal discharge, and signs of bronchopneumonia were found in all at necropsy. According to the authors, the death of these animlas was primarily due to disability produced by the extreme irritation, rather than to any systemic effect of the resin.