Reaction products of 2-(chloromethyl)oxirane and glycerol

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

migrated information: read-across based on grouping of substances (category approach)

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:

Groups of 10 male rats (80-104 gm.) were exposed five days a week for seven hours, for a total of 50 exposures, to air saturated with the vapor of EPON 562. Similarly, a group of 10 control rats were exposed to uncontaminated air. The animals were exposed in cylindrical steel chambers of 210-liter capacity at 20±1°C. The rats were observed for signs of intoxication during and after each exposure. Individual weights were recorded weekly. At the end of the experimental period, the rats were killed and examined for gross changes. Representative tissues were taken for histologic study, and the organ/body weight ratios were determined on liver, lungs, and kidneys for statistical analysis.

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:

rat

Strain:

Long-Evans

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 80 - 104 g

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Remarks:

The animals were exposed in cylindrical steel chambers of 210-liter capacity at 20±1°C.

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindrical steel chambers of 210-liter capacity at 20±1°C.
- Method of holding animals in test chamber: free in chamber
- Temperature, humidity, pressure in air chamber: 20±1°C.
- Air flow rate: 15 L/min

TEST ATMOSPHERE
- Brief description of analytical method used: none
- Samples taken from breathing zone: no

Other:
Air was substantially saturated with EPON 562 by passage through two fritted glass bubblers connected in series. The airflow rate was held constant at 15 liters per minute. A preliminary saturation period of about an hour insured greater than 95% saturation of the air prior to the exposure of animals. No analytical check was made of the concentration, since it was too low to permit accuracy of determination in either case.

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

not applicable

Duration of treatment / exposure:

seven hours

Frequency of treatment:

5 days / week ( for 50 exposures)

Doses / concentrations

Remarks:

Doses / Concentrations:
air saturated with the vapour of EPON 562
Basis:
no data

No. of animals per sex per dose:

10

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

The rats were observed for signs of intoxication during and after each exposure. Individual weights were recorded weekly, and mean weight changes were graphed in the form of growth curves.

Sacrifice and pathology:

At the end of the experimental period, the rats were decapitated under light ether anesthesia, exsanguinated, and examined for gross changes. Representative tissues were taken for histologic study, and the organ/body weight ratios were determined on liver, lungs, and kidneys for statistical analysis.

Other examinations:

no other examinations reported

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Aside from a very slight incrustation of the eyelids of some animals, with red-brown exudate, no rat showed any signs of toxicity or irritation attributable to the exposure. 1 rat of the DGR group & 2 in the .control group died between the 3. & 4.th week.

Mortality:

mortality observed, treatment-related

Description (incidence):

Aside from a very slight incrustation of the eyelids of some animals, with red-brown exudate, no rat showed any signs of toxicity or irritation attributable to the exposure. 1 rat of the DGR group & 2 in the .control group died between the 3. & 4.th week.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Analysis of variance showed no significant difference in mean weight gains or in organ/body weight ratios (P = < 0.05).

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

At necropsy of the animals that died during the exposure period, bronchopneumonia was found. No significant gross or microscopic lesions were found in the surviving animals.

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOAEC

Effect level:

other: saturated vapour

Based on:

test mat.

Sex:

male

Basis for effect level:

other: No clinical signs, very slight incrustation of the eyelids; no significant gross or microscopic lesions.

Remarks on result:

not determinable

Remarks:

no NOAEC identified

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The series of 50 exposures to the saturated vapors of EPON 562 and DGR was singularly free of untoward effects. Aside from a very slight incrustation of the eyelids of some animals, with red-brown exudate, none of the rats showed any signs of toxicity or irritation attributable to the exposure. One rat of the DGR group and two in the .control group died between the third and fourths weeks. At necropsy of these animals, bronchopneumonia was found. No significant gross or microscopic lesions were found in the surviving animals. Analysis of variance showed no significant difference in mean weight gains or in organ/body weight ratios (P = < 0.05).

Applicant's summary and conclusion

Conclusions:

The study was considered to be of high reliability (reliability Klimisch 2), because of the detailed documentation of the methods used and the results obtained. The test material, EPON 562 did not induce mortality and treatment-related clinical signs in treated rats. No practical or systemic toxicity hazard could be associated with exposure to the vapors of the resin.

Executive summary:

The repeated toxicity of the read-across substance polyglycidyl ether of substituted glycerine (EPON 562) was investigated by Hine et al. (1958). The effect of inhalation of the EPON 562 was tested on rats (male Long Evans). Groups of 10 male rats were exposed five days a week for seven hours, for a total of 50 exposures, to air saturated with the vapour of EPON 562. Similarly, a group of 10 control rats was exposed to uncontaminated air. The animals were exposed in cylindrical steel chambers of 210-liter capacity at 20±1C. Air was substantially saturated with EPON 562 by passage through two fritted glass bubblers connected in series. The airflow rate was held constant at 15 liters per minute. A preliminary saturation period of about an hour insured greater than 95% saturation of the air prior to the exposure of animals. No analytical check was made of the concentration, since it was too low to permit accuracy of determination in either case. The rats were observed for signs of intoxication during and after each exposure. Individual weights were recorded weekly, and mean weight changes were graphed in the form of growth curves. At the end of the experimental period, the rats were decapitated under light ether anesthesia, exsanguinated, and examined for gross changes. Representative tissues were taken for histologic study, and the organ/body weight ratios were determined on liver, lungs, and kidneys for statistical analysis. The series of 50 exposures to the saturated vapors of EPON 562 was singularly free of untoward effects. Aside from a very slight incrustation of the eyelids of some animals, with red-brown exudate, none of the rats showed any signs of toxicity or irritation attributable to the exposure. Two rats in the control group died between the third and fourth weeks. At necropsy of these animals, bronchopneumonia was found. No significant gross or microscopic lesions were found in the surviving animals. Analysis of variance showed no significant difference in mean weight gains or in organ/body weight ratios (P≤0.05).