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Toxicological information

Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 1. The measured atmospheric concentrations are not reported. 2. No ophthalmological examinations were performed. 3. Food consumption was not measured. 4. It is not reported how many nasal sections were examined histopathologically.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1984
Reference Type:
other: presentation from poster session
Title:
Inhalation toxicity of ethylamine (EA) vapor in F-344 rats
Author:
Lynch, D., et al.
Year:
1988
Bibliographic source:
Poster session for presentation at the 27th society of toxicology meeting Dallas, TX, February 15-19, 1988

Materials and methods

Principles of method if other than guideline:
no data
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
CAS 75-04-7 (ethylamine), solution of 70% (reagent grade) in water

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
- Weight at study initiation:
- Males: 262 +/- 5 g
- Females: 159 +/- 3 g

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Remarks on MMAD:
MMAD / GSD: no data
Details on inhalation exposure:
- Exposure period: 6 h/day, 5 days/week for 24 weeks.
- Route of administration: inhalation (whole body).
- Doses: 0, 18, 184 and 922 mg/m3.
- Air changes: 12-15/hour.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
- Method: Wilks-Miran infrared analyzer
- Sampling times: 2-4 times per hour
Duration of treatment / exposure:
24 weeks
Frequency of treatment:
6 hours/day, 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 10, 100 and 500 ppm (0, 18, 184, and 922 mg/m3)
Basis:

No. of animals per sex per dose:
- Number of animals: 30/sex/treatment
Control animals:
yes

Examinations

Observations and examinations performed and frequency:
- Clinical signs and mortality: twice daily
- Body weight: on the day preceding the first exposure and at 2-week intervals throughout the study period
- Hematology (on 10/sex/treatment only at terminal sacrifice): hemoglobin, hematocrit and complete and differential blood count
- Biochemistry (at 30 day and terminal sacrifice): alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, lactate dehydrogenase, blood urea nitrogen, creatinine and sorbitol dehydrogenase
- Post-exposure period: No

- Examinations were performed on 6 animals/sex/treatment after 30 and 60 days of exposure and 12-18/sex/treatment at terminal sacrifice. These animals were necropsied and the following analyses were performed:
- Organ weights: lungs, liver, kidney and heart
- Macroscopic: complete gross necropsy
- Microscopic: lungs, liver, kidneys, heart, aorta, spleen, pancreas, tracheobronchial lymph nodes, mesenteric lymph nodes, adrenals, testes, seminal vesicles, ovaries, uterus, trachea, eye, bone marrow (sternum), thymus and nares (at terminal sacrifice only)
Other examinations:
Electrocardiograms of 10 anesthetized rats at terminal sacrifice.
Statistics:
Multiple t-tests, multivariate ANOVA, Kruskal-Wallis test and Chi-square test

Results and discussion

Results of examinations

Clinical biochemistry findings:
effects observed, treatment-related
Details on results:
TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
- Mortality: one male and one female at 500 ppm
- Clinical signs: at 500 ppm rats kept their eyes closed and buried their noses in their fur during the entire exposure period
- Body weight gain: significantly reduced at 500 ppm for both males and females
- Clinical chemistry: no treatment-related effects
- Haematology: no treatment-related effects
- Organ weights: at 500 ppm significantly increased relative weights of lung, kidney and heart for both males and females, probably due to the decreased body weights seen at this exposure level
- Gross pathology: no treatment-related signs
- Histopathology: at 500 ppm moderate to marked atrophic rhinitis in the nasal passages, principally in the anterior half and characterized by: purulent exudate of in the nasal meatuses; chronic, active inflammation (often ulcerative), necrosis and loss of the cartilaginous nasal septum, loss of bony turbinates and squamous metaplasia of nasal epithelium
- Other: no consistent treatment-related effects were seen in electrocardiography, although the QT-interval of male rats at 500 ppm was significantly longer than controls
- No adverse effects on male and female gonads were observed

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
100 ppm
Sex:
male/female
Dose descriptor:
LOAEL
Effect level:
500 ppm
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

NOAEL = 100 ppm (184 mg/m3) based on decreased body weights and histopathological changes of the nasal passages.

Applicant's summary and conclusion