Trimethylamine

Repeated dose toxicity: inhalation

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: Not according to guideline and not GLP but provides basic repeated exposure toxicity data.

Data source

Reference

Reference Type:

publication

Title:

On the toxic effect of low trimethylamine concentrations

Author:

Rotenberg, I., and Mashbits, F.

Year:

1967

Bibliographic source:

In Russian. Gig. Trud. Prof. Zabol. 4:26-30.

Materials and methods

Principles of method if other than guideline:

no details on method given

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Trimethylamine

EC Number:

200-875-0

EC Name:

Trimethylamine

Cas Number:

75-50-3

Molecular formula:

C3H9N

IUPAC Name:

N,N-dimethylmethanamine

Details on test material:

CAS 75-50-3 (trimethylamine), purity not specified

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

seven months

Frequency of treatment:

5 hours per day

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

25 mg/m³ air

Remarks:

25 mg/m³ (= 0.025 mg/L = 10 ppm)

Doses / concentrations 2

Dose / conc.:

75 mg/m³ air

Remarks:

75 mg/m³ (= 0.075 mg/L = 31 ppm)

No. of animals per sex per dose:

Groups of 12 rats (sex not specified)

Control animals:

yes, concurrent no treatment

Examinations

Observations and examinations performed and frequency:

no details given

Sacrifice and pathology:

no details given

Other examinations:

no details given

Statistics:

no details given

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

The animals were irritated and aggressive during the first 3-4 weeks of exposure. Diarrhoea was observed 20-30 minutes after the start of exposure and ceased after 2-3 hours. Beginning from the second month of exposure, the feces of the animals normalised, and their behaviour did not differ from that of the controls.

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Body weight did not show any differences between control and treated animals.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Protein spectrum of the blood did not show any differences between control and treated animals.
Investigation of the leukocyte formula demonstrated a reduction of the lymphocyte count, accompanied by a relative neutrophilia in the 75 mg/m³ (31 ppm) group from the fourth month of exposure.

Clinical biochemistry findings:

not specified

Description (incidence and severity):

Detoxifying function of the liver did not show any differences between control and treated animals.

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Measurement of the weight ratios of the internal organs demonstrated an increased weight of the adrenals.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Pathological examination demonstrated bronchopneumonia and haemorrhage into the lung tissues, with destruction of the interalveolar septa, signs of passive hyperaemia, and isolated haemorrhages in the liver, kidneys, and spleen in the 75 mg/m³ (31 ppm) group. Analogous, though less marked, changes were also observed in the animals of the 25 mg/m³ (10 ppm) group.
Morphological changes in the lung, liver, kidneys, spleen at 31 ppm with similar, less marked changes at 10 ppm.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

Pathological examination demonstrated bronchopneumonia and haemorrhage into the lung tissues, with destruction of the interalveolar septa, signs of passive hyperaemia, and isolated haemorrhages in the liver, kidneys, and spleen in the 75 mg/m³ (31 ppm) group. Analogous, though less marked, changes were also observed in the animals of the 25 mg/m³ (10 ppm) group.
Morphological changes in the lung, liver, kidneys, spleen at 31 ppm with similar, less marked changes at 10 ppm.

Histopathological findings: neoplastic:

not specified

Details on results:

The animals were irritated and aggressive during the first 3-4 weeks of exposure. Diarrhoea was observed 20-30 minutes after the start of exposure and ceased after 2-3 hours. Beginning from the second month of exposure, the feces of the animals normalised, and their behaviour did not differ from that of the controls.
Body weight, protein spectrum of the blood and detoxifying function of the liver did not show any differences between control and treated animals.
Measurement of the weight ratios of the internal organs demonstrated an increased weight of the adrenals.
Investigation of the leukocyte formula demonstrated a reduction of the lymphocyte count, accompanied by a relative neutrophilia in the 75 mg/m³ (31 ppm) group from the fourth month of exposure.
Pathological examination demonstrated bronchopneumonia and haemorrhage into the lung tissues, with destruction of the interalveolar septa, signs of passive hyperaemia, and isolated haemorrhages in the liver, kidneys, and spleen in the 75 mg/m³ (31 ppm) group. Analogous, though less marked, changes were also observed in the animals of the 25 mg/m³ (10 ppm) group.
Morphological changes in the lung, liver, kidneys, spleen at 31 ppm with similar, less marked changes at 10 ppm.

Effect levels

Dose descriptor:

LOAEC

Effect level:

25 mg/m³ air

Sex:

not specified

Basis for effect level:

other: no details on basis given

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

LOAEC = 0.025 mg/L air

Executive summary:

Rotenberg and Mashbits performed in 1967 a subchronic test on 12 rats with trimethylamine by the route of inhalation. The test duration was 7 months, the substance was administered 5 hours per day at concentrations of 0.025 and 0.075 mg/L. The animals were irritated and aggressive during the first 3-4 weeks of exposure. Diarrhoea was observed 20 – 30 minutes after the start of exposure and ceased after 2-3 hours. Beginning from the second month of exposure, the faeces of the animals normalized, and their behaviour did not differ from that of the controls. Body weight, protein spectrum of the blood and detoxifying function of the liver did not show any differences between control and treated animals. Measurement of the weight ratios of the internal organs demonstrated an increased weight of the adrenals. Investigation of the leukocyte formula demonstrated a reduction of the lymphocyte count, accompanied by a relative neutrophilia in the 75mg/m³ (31 ppm) group from the fourth month of exposure. Pathological examination demonstrated bronchopneumonia and haemorrhage into the lung tissues, with destruction of the interalveolar septa, signs of passive hyperaemia, and isolated haemorrhages in the liver, kidneys, and spleen in the 75 mg/m3 (31 ppm) group. Analogous, though less marked, changes were also observed in the animals of the 25 mg/m³ (10 ppm) group. Morphological changes in the lung, kidneys, spleen at 31 ppm with similar, less marked changes at 10 ppm.