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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to OECD guideline, acceptable with restrictions (haematology, clinical chemistry and urinalysis parameters were not tested)

Data source

Reference
Reference Type:
publication
Title:
Toxicology and carcinogenesis studies of Allyl Glycidyl Ether (CAS No. 106-92-3) in Osborne-Mendel rats and B6C3F1 Mice (inhalation studies).
Author:
National Toxicology Program (NTP)
Year:
1990
Bibliographic source:
NTP Technical Report 376, NIH Publication No. 90-2831, U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
haematology, clinical chemistry and urinalysis parameters were not tested
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): Allyl Glycidyl Ether
- Physical state: clear colorless liquid
- Analytical purity: 99 %

Test animals

Species:
rat
Strain:
Osborne-Mendel
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CAMM Research Institute (Wayne, NJ)
- Age at study initiation: 8 weeks
- Weight at study initiation (mean weight): male 261-271 g, female 178-188 g
- Housing: 1 per cage
- Diet (e.g. ad libitum): NIH 07 Rat and Mouse Ration (Zeigler Bros., Inc., Gardners, PA)
- Water (e.g. ad libitum): Automatic watering system
- Acclimation period: 21 days

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Vapor Generation System: No additional preparation of the liquid allyl glycidyl ether (AGE) was necessary before introduction into the vapor generation system. The liquid was pumped from a stainless steel reservoir to a vaporizer by a stable micrometering pump with adjustable pump rates.
- Temperature, humidity in air chamber: 20.6-26.7 °C, 32-75%

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatography with a flame ionization detector
- Samples taken from breathing zone: yes
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Exposure concentrations of AGE were within ± 10% of the target concentrations.
Duration of treatment / exposure:
90 days
Frequency of treatment:
6 hours per day, 5 days per week
Doses / concentrations
Remarks:
Doses / Concentrations:
4, 10, 30, 100 and 200 ppm (equivalent to 19, 47, 140, 467, 934 mg/m3)
Basis:

No. of animals per sex per dose:
10
Control animals:
yes, sham-exposed

Examinations

Observations and examinations performed and frequency:
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: 2 times per day

BODY WEIGHT: Yes
- Time schedule for examinations: before exposure, at weekly intervals

FOOD CONSUMPTION: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes, on all animals
HISTOPATHOLOGY: Yes, on all animals. The tissue examined were adrenal glands, bone marrow, brain, colon, duodenum, esophagus, heart, kidneys, larynx, liver, lungs and bronchi, mammary gland, mandibular lymph nodes, nasal cavity, pancreas, parathyroid glands, pituary gland, salivary glands, seminal vesicles/prostate/testes or ovaries/uterus, skin, spleen, stomach, thymus, thyroid gland, trachea and urinary bladder in the control and high dose groups. In the lower dose groups, esophagus, larynx, lungs and bronchi, nasal cavity, thyroid gland and trachea were examined.
Other examinations:
Liver weights of all animals at all dose levels were determined.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
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:
effects observed, treatment-related
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY: No mortality was observed. Clinical signs not indicated.

BODY WEIGHT AND WEIGHT GAIN: The body weight gain of male rats exposed to 10, 30, 100  and 200 ppm were decreased (93, 87, 81 and 76 % relative to the  controls). The body weight gain of female rats exposed to 30, 100 and 200  ppm were also decreased (93, 92 and 87 % relative to the controls). 

ORGAN WEIGHTS: The absolute liver weight of male rats exposed to 4, 10,  30, 100 an 200 ppm decreased (114, 109, 108, 86 and 86 % relative to the  controls). Relative liver weights were 122, 117, 122, 106 and 115 %  relative to the controls at the same doses. Changes in absolute and relative liver weights in males were primarily due to a decrease in body weight. Relative liver weight was statistically increased at 10 ppm and above in females (dose-related; 120-132% of control). Absolute liver weights were also increased at 10 ppm and above (110-116%; not clear dose-related).

GROSS PATHOLOGY: no data

HISTOPATHOLOGY: NON-NEOPLASTIC: Inflammation, epithelial hyperplasia and/or squamous metaplasia of the nasal passage were observed in rats of all dose groups. Those lesions were exposure related with a higher incidence and greater severity with increasing exposure concentration. Hyperostosis and focal fibrosis of the nasal passage were observed in most rats at 30 ppm and above, with a high incidence and greater severity with increasing exposure concentration. Metaplasia of the larynx, trachea and bronchi were seen in rats exposed to 10, 30, 100 and 200 ppm. Focal inflammatory changes of the lungs were also seen, but were not treatment related as it was also seen in control animals.

Effect levels

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Dose descriptor:
NOAEC
Remarks:
local effects
Effect level:
< 19 mg/m³ air
Sex:
male/female
Basis for effect level:
other: histopathological findings in the nasal passage at this dose level
Dose descriptor:
LOAEC
Remarks:
local effects
Effect level:
19 mg/m³ air
Sex:
male/female
Dose descriptor:
NOAEC
Remarks:
systemic effects
Effect level:
934 mg/m³ air
Sex:
male/female
Basis for effect level:
other: highest dose tested

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

A chronic inflammatory change characteristic of a viral pneumonia was seen in all groups with a higher incidence and severity in control animals. Positive titers to pneumonia virus of mice were seen in 9/10 rats tested at the beginning and at the end of the studies.

Applicant's summary and conclusion