Triethylamine

Endpoint summary

Description of key information

Lynch et al. (1990): Subchronic Inhalation of Triethylamine Vapor in Fischer-344 Rats: Organ System Toxicity. Method comparable to Guideline. Rats, exposed to 0, 25 and 247 ppm for 28 weeks.

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEC

1 020 mg/m³

Additional information

A subchronic study (inhalation of triethylamine vapour in fischer-344 rats, Lynch et al., 1990) was taken as the key study for the repeated inhalation toxicity endpoint. No adverse effects were observed in Fischer-344 rats exposed to 25 or 247 ppm, 6hr/day, 5 days/week for 28 weeks. The study is well-documented and allowed to evaluate the results. One male rat died during exposure period (8 week), the other deaths (1 female at 25 ppm, week 6, 2 females at 247 ppm, week 3, accidentally) were considered to be not treatment related. The body weight gain was slightly reduced in males (dose-related). No hematologic influences and additionally only incidental changes in clinical chemistry (ALAT, creatinine and sorbitol dehydrogenase) were found in treated animals. Chronic inflammations of lungs, liver lesions and neoplastic lesions were observed in all groups, including the controls. "At 247 ppm TEA the rats kept their eyes closed and noses buried in their fur during the entire exposure period". These findings could not be attributed to chemical exposure (argued by the author). According to the author the lung lesions were associated with viral infection. Any neoplastic lesions in the experimental animals were not associated with exposure to the test substance. Triethylamine exposure also led to degeneration of heart muscle fibers (males, 25 ppm after 125 exposures, Lynch et al., 1990), but since this degeneration was only minimal and occurred so late in the exposure period, one cannot ascribe importance to this findings. Additionally no changes in electrocardiograms were found.

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.

There are controversial results from the older studies concerning repeated inhalation toxicity. When rats were exposed to 1000 ppm triethylamine for 10 days, moderate necrotizing inflammation of the nasal cavity occurred in all male and female animals. Some rats had slight to moderate perivascular edema of the lungs, slight to moderate squamous metaplasia of the trachea and moderate thymic atrophy (refer to USEPA, 1996 of IUCLID file). Tkachev had exposed rats to lower concentrations of triethylamine during 3 month (Tkachev, 1970). Changes in lungs, brain and liver were detected in albino rats exposed to 3.14 ppm. There was infiltration of the perivascular connective tissue by white blood cells in lungs, also thickening of the interalveolar walls and shedding of the alveolar epithelium. In the brain, there was swelling, disruption of nuclei, necrosis, disappearance of neurons, reduced cytochrome oxidase activity accumulation of lipids in the cerebral cortex and reduced staining intensity of sulfhydryl groups. In the liver there was a reduction in glycogen content. Exposure to lower doses (0.039 or 0.41 ppm) did not produce these changes. Brieger and Hodes (1951) exposed rabbits to 50 or 100 ppm triethylamine for 6 weeks. All animals survived, but lung and eye irritation was a common observation. Exposure to 100 ppm also caused parenchymatous degeneration and occasionally inflammatory processes in liver and kidney.

Justification for classification or non-classification

Due to the corrosivity of TEA and the fact that local effects prevail over systemic effects, classification is not warranted for STOT-RE according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008: