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Toxicological information

Repeated dose toxicity: inhalation

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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:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well-documented publication, which meets basic scientific principles
Cross-reference
Reason / purpose:
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

Reference
Name:
Unnamed
Type:
Constituent
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 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 (P0.05).