Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
other: publication
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically reasonable method with some deficiencies in documentation on the registered substance itself.

Data source

Reference
Reference Type:
publication
Title:
"The toxicology of glycidol and some glycidyl ethers"
Author:
Hine , Kodoma , Wellington , Dunlap , Anderson
Year:
1956
Bibliographic source:
Hine, C. H., J. K. Kodoma, J. S. Wellington, M. K. Dunlap, H. H. Anderson: "The toxicology of glycidol and some glycidyl ethers", Arch. Ind. Health 14, 250 (1956)

Materials and methods

Principles of method if other than guideline:
A group of ten male Long-Evans rats was exposed to an isopropyl glycidyl ether concentration of 400 ppm (vapour), 7 hours daily, 5 days per week for 10 weeks.
GLP compliance:
no
Remarks:
conducted prior to GLP implementation

Test material

Constituent 1
Chemical structure
Reference substance name:
2,3-epoxypropyl isopropyl ether
EC Number:
223-672-9
EC Name:
2,3-epoxypropyl isopropyl ether
Cas Number:
4016-14-2
Molecular formula:
C6H12O2
IUPAC Name:
2-[(propan-2-yloxy)methyl]oxirane
Test material form:
not specified
Details on test material:
No details available

Test animals

Species:
rat
Strain:
Long-Evans
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: commercial laboratory in Gilroy, Calif.

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
not specified
Remarks on MMAD:
MMAD / GSD: no data
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: chambers of 200 liters capacity
- Method of holding animals in test chamber:
- Source and rate of air:
- Method of conditioning air: The constant-metering device, similar to that described in the section on acute exposures (The motor-driven syringe assembly delivered measured amounts of the test compound from a 10 ml. Luer-Lok syringe into an evaporator through which metered air moved, at a uniform rate.), delivered the liquid in measured amounts to the evaporator, where they were vaporized in the air entering the chamber. The air in the chamber was allowed to equilibrate to a theoretical 95% to 99% of the desired concentration before the animais were introduced.
- Air flow / change rate: air flow ranged from 11.7 to 22.0 liters per minute (3.5 to 6.6 air changes per hour)

TEST ATMOSPHERE
- Brief description of analytical method used: Vapor concentrations were monitored by frequent analysis of air drawn from a sampling port and absorbed in a magnesium chloride and hydrochloric acid solution
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Vapor concentrations were monitored by frequent analysis of air drawn from a sampling port and absorbed in a magnesium chloride and hydrochloric acid solution.
Duration of treatment / exposure:
10 Weeks
Frequency of treatment:
7 hours daily, 5 days per week
Doses / concentrations
Remarks:
Doses / Concentrations:
400 ml/m³
Basis:
no data
No. of animals per sex per dose:
10 male animals
Control animals:
yes
Details on study design:
No details available
Positive control:
No details available

Examinations

Observations and examinations performed and frequency:
The rats were carefully observed at intervals during the exposure and were weighed weekly.
Sacrifice and pathology:
At the end of the experimental period all survivors were decapitated under light ether anesthesia, and blood was collected for hemoglobin determination (Sahli method). At necropsy the animals were carefully examined for gross pathologic changes, and the lungs, livers, and kidneys of all animals were freed of connective tissue and excess moisture and weighed for determination of organ/body weight ratios. Sections of these tissues were retained for histologic examination, and also tissues from alternate animals, as follows: brain, thyroid, thymus, heart, stomach, intestine, pancreas, adrenal, testis, and bladder.
Organ/body weight ratios, percentage weight gain, and hemoglobin concentrations of the experimental animals were compared with those of the controls by the "Student" t-test.
Other examinations:
No details available
Statistics:
Organ/body weight ratios, percentage weight gain, and hemoglobin concentrations of the experimental animals were compared with those of the controls by the "Student" t-test.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Description (incidence and severity):
no mortality occurred
Mortality:
no mortality observed
Description (incidence):
no mortality occurred
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
weight loss or decreased weight gain
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Description (incidence and severity):
Organ/body weight ratio for liver, kidney unchanged
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
Slight ocular irritation and respiratory distress were seen, similar to the signs shown with glycidol at the same level. However, there was a significantly greater decrease in the mean weekly weight gains (P=<0.01).
At necropsy some decrease in peritoneal fat was seen, and the lungs of 4 of the 10 rats appeared somewhat emphysematous; two showed some mottling of the liver. One of the latter showed confluent pneumonia on microscopic examination, but all other sections examined were within normal limits.

Effect levels

open allclose all
Dose descriptor:
LOEC
Effect level:
400 ppm
Based on:
test mat.
Sex:
male
Basis for effect level:
other: decreased bodyweight gain, hemoglobin increase
Dose descriptor:
NOEC
Effect level:
400 ppm
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Body/organ weight ratios liver, kidney; mortality

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The method was conducted scientifically reasonable with some deficiencies in documentation. It can be used to support the data of the key study via oral application.
Executive summary:

A group of ten male Long-Evans rats was exposed to an isopropyl glycidyl ether concentration of 400 ppm (400 ml/m³), 7 hours daily, 5 days per week for 10 weeks. Slight eye irritation and laboured breathing were observed; the body weight gain of the exposed animals was less than that of the controls. Mild emphysema was found in the lungs of four of the ten rats. [Hine, C. H., J. K. Kodoma, J. S. Wellington, M. K. Dunlap, H. H. Anderson: "The toxicology of glycidol and some glycidyl ethers", Arch. Ind. Health 14, 250 (1956)]