Propylamine

Repeated dose toxicity: inhalation

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1984

Reference 2

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

Test material information

Constituent 1

Reference substance name:

Ethylamine

EC Number:

200-834-7

EC Name:

Ethylamine

Cas Number:

75-04-7

IUPAC Name:

ethanamine

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 or test system 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

1

Dose descriptor:

NOAEL

Effect level:

100 ppm

Sex:

male/female

2

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.