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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: Similar to guideline study; not GLP

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Subchronic inhalation of triethylamine vapor in Fisher-344 rats: organ system toxicity
Author:
Lynch et al.
Year:
1990
Bibliographic source:
Toxicol Ind Health 6(3/4): 403-414.
Reference Type:
other: report
Title:
Narrative summary of histomorphological findings from F344 rats exposed by inhalation to allylamine (4 and 40 ppm) and triethylamine (25 and 250ppm) for 30, 60 and 120 days
Author:
no author
Year:
1984
Bibliographic source:
NIOSH
Reference Type:
other: USEPA TSCA 8(d) submission
Title:
untitled
Author:
no author
Year:
1987
Bibliographic source:
TSCATS, OTS 0515254, Doc.I.D. 86-870000816, Virginia Chemicals
Report date:
1987

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
two dose levels were used
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 452 (Chronic Toxicity Studies)
Deviations:
yes
Remarks:
two dose levels were used
Principles of method if other than guideline:
In the present study only two dose levels were used in addition to the concurrent control group. The duration of the study is 28 weeks. Not all examinations are performed.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Triethylamine
EC Number:
204-469-4
EC Name:
Triethylamine
Cas Number:
121-44-8
Molecular formula:
C6H15N
IUPAC Name:
triethylamine
Details on test material:
CAS 121-44-8 (triethylamine), purity >99.9% was obtained from MCB Manufacturing Chemists, Inc., Norwood, OH
Lot number G3M04

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
Strain:Weanling caesarean-derived Fisher F344 [CDF (F-344)/Crl BR]
Rats were screened for serological evidence of Mycoplasma pulmonis infection prior to the initiation of exposures and all results were negative.
- Source: Charles River breeding Laboratories, Wilmington MA
- Age at study initiation: not reported
- Weight at study initiation: not reported
- Fasting period before study: no
- Housing: individually
- Diet (e.g. ad libitum): except during the exposure periods.
- Water (e.g. ad libitum): except during the exposure periods.
- Acclimation period: 2 weeks

ENVIRONMENTAL CONDITIONS
- Air changes (per hr): 12-15/hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
not specified
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Exposures were conducted in three 4.5 m³ stainless steel and glass inhalation chambers (Hinners et al., 1968) operated under dynamic flow conditions.

- Temperature, humidity in air chamber: 23 ± 3°C and 50 ± 10% RH, respectively.
- Air flow rate: 12-15 air changes per hr
- Treatment of exhaust air: A fresh batch of TEA was used in the generation reservoir each day.

TEST ATMOSPHERE
- Brief description of analytical method used: Wilks-Miran 1A Infrared Analyzer (Foxboro Analytical, Norwalk, CT) using the following instrument settings: wavelength 9 µm, pathlength 6.2 m, slit 1.0 mm. The instrument was calibrated by the closed loop calibration method. Adjustments were made to the generation system, as required, to maintain the exposure levels at the targeted concentrations.
- Samples taken from breathing zone: yes. TEA concentrations in the chamber were monitored 2-4 times per hour using a Wilks-Miran 1A Infrared Analyzer (Foxboro Analytical, Norwalk, CT)

VEHICLE (if applicable) no
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
2-4 times/hour with a Wilks-Miran Infrared Analyzer
Duration of treatment / exposure:
28 weeks
Frequency of treatment:
6 hours/day, 5 days/week
127 maximum exposure days
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 25 and 247 ppm  (0, 103 and 1020 mg/m3)
Basis:
nominal conc.
No. of animals per sex per dose:
50/sex/dose
Control animals:
yes
Details on study design:
- Dose selection rationale: Exposure concentrations were selected to provide comparisons to previous toxicity determinations conducted in this laboratory with diethylamine at 25 and 250 ppm (Lynch et al., 1986).
- Rationale for animal assignment (if not random): randomised
Positive control:
no

Examinations

Observations and examinations performed and frequency:
Mortality/clinical signs: twice daily
Body weight: 2-weekly
Sacrifice and pathology:
10/sex/treatment sacrificed after ~30 and ~60 days of exposure, 20 after  ~ 125 days of exposure (10 in controls) 
Hematology: at each scheduled sacrifice: Hb, hematocrit, red blood cells,  white blood cells (total and differential count)
Clinical chemistry: at each scheduled sacrifice: ALAT, ASAT, creatine  phosphokinase, blood urea nitrogen, creatinine, LDH, sorbitol  dehydrogenase. EGC at terminal sacrifice in 9-11 rats/sex/treatment
Necropsy Organ weights: lungs, liver, kidneys and heart
Macroscopic evaluation: complete
Histopathology: lungs, liver, heart, spleen, kidneys, tracheobronchial  lymphnodes, adrenals, urinary bladder, testes, seminal vesicles, uterus,  ovaries, trachea, eyes, nasal passages (according to Buckley, 1985)
Statistics:
t-test, multivariate analysis of variance,  Kruskal-Wallis and chi-square test

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
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:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Histopathological findings: neoplastic:
effects observed, treatment-related
Details on results:
Mean chamber concentrations: 0, 24.8 and 247.3 ppm
Observations: Mortality: 1 female at 25 ppm (week 6), 1 male(week 8) and 2 females  (week 3)(both accidentally) at 247 ppm 
Clinical signs: at 247 ppm closed eyes and noses buried in fur Body weight gain: slightly reduced in males (dose-related)
Hematology: no treatment related effects
Clinical chemistry: incidentally increases of  ALAT, creatinine and  sorbitol dehydrogenase. EGC within normal ranges
Macroscopy: no treatment related effects
Histopathology:  Chronic inflammation of the lungs in all treated and control animals  after 30 and 125 exposures. Male lung weights were increased in a concentration-dependent manner, although the changes were not statistically significant or accompanied by any histopathology. Liver necrosis(focal) in all treated and control animals after 125  exposures. Minimal focal necrosis of myofibers of the heart in males at 25 ppm after 125 exposures
Neoplastic lesions: nephroblastoma in one female at 25 ppm after 30  exposures, pituitary adenoma in one male at 247 ppm after 125 exposures,  thyroid follicular cell adenoma in one control female after 125 exposures

Effect levels

open allclose all
Dose descriptor:
NOAEC
Remarks:
systemic effects
Effect level:
1 020 mg/m³ air
Sex:
male/female
Basis for effect level:
other: clinical signs
Dose descriptor:
NOAEC
Remarks:
local effects, irritation
Effect level:
103.3 mg/m³ air
Sex:
male/female
Basis for effect level:
other: no effects
Dose descriptor:
LOAEC
Remarks:
eye and noses irritation
Effect level:
1 020 mg/m³ air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: irritation effects

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

1. Lung lesions were associated with viral infection according to the author of the report.

2. Neoplastic lesions were not associated with exposure to the test substance.

3. There was no cardic muscle degenerations or any changes in electrocardiogramms.




Applicant's summary and conclusion

Conclusions:
Triethylamine do not induce systemic toxicity in rats if inhaled.
Executive summary:

Male and female F-344 rats were exposed at 0, 25, or 247 ppm triethylamine (TEA) vapor, 6 hr per day, 5 days per week for up to 28 weeks in order to characterize the subchronic organ system toxicity. Rats were weighed biweekly and scheduled sacrifices were performed following about 30, 60, and 120 days of exposure. No statistically significant treatment-related effects on organ weights, hematology, clinical chemistry, or electrocardiographic indices were observed. Body weight gain was not affected by TEA treatment. No physiologic or pathologic evidence of cardiotoxicity was seen in rats exposed to either TEA concencentrations for up to 28 weeks. No gross or histopathological lesions attributable to TEA exposure were noted in any of the organs examined, including the nasal passages.

Based on the study results 25 ppm (corresponds to 103.3 mg/m³) is considered to be a NOAEC for local effects and irritation, while 247 ppm, the highest concentration tested (corresponds to 1020 mg/m³), repesents a NOAEC for systemic effects and simultaneously a LOAEC for eye and nose irritation.