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Administrative data

Description of key information

Oral:

Amoore et al. (1978) repeated dose toxicity of trimethylamine hydrochloride in male Sprague-Dawley rats (90-day study, 0.04. 0.08, 0.16, 0.31, and 0.62 % trimethylamine hydrochloride in diet (corresponding to 0, 20, 40, 79, 150 and 310 mg/kg bw of trimethylamine). NOAEL of 0.16% diet TMA-HCl (= 130 mg/kg bw/day TMA-HCl (rounded from 128) = 79 mg/kg bw TMA) was established.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: acceptable well-documented publication, which meets basic scientific principles.
Qualifier:
no guideline followed
Principles of method if other than guideline:
90 day feeding trial with trimethylamine (applied as the hydrochloride) on Sprague-Dawley rats
GLP compliance:
no
Limit test:
no
Specific details on test material used for the study:
no details given
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
- Source: not reported
- Age: 4 weeks 
- Mean weight at study initiation: 90 g
Route of administration:
oral: feed
Details on route of administration:
We used a diet composed of 30 % dextrose, 20 % cornmeal, 20 % soybean meal, 10 % casein, 9 % corn starch, and 5 % corn oil, with 4 % salt mixture and 2 % of a mixture of vitamins triturated in dextrose
Vehicle:
not specified
Details on oral exposure:
no details given
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
continuous
Dose / conc.:
0 other: % TMA-HCL in diet (nominal)
Dose / conc.:
0.04 other: % TMA-HCL in diet (nominal)
Dose / conc.:
0.08 other: % TMA-HCL in diet (nominal)
Dose / conc.:
0.16 other: % TMA-HCL in diet (nominal)
Dose / conc.:
0.31 other: % TMA-HCL in diet (nominal)
Dose / conc.:
0.62 other: % TMA-HCL in diet (nominal)
No. of animals per sex per dose:
5-6 males per group
Control animals:
yes
Details on study design:
- Rationale for animal assignment (if not random): weight-matched groups
Positive control:
none
Observations and examinations performed and frequency:
- Mortality/clinical observations: interval not specified 
- Body weight: interval not specified
- Haematology: Day 80 (counts of erythrocytes, leukocytes, hematocrit and hemoglobin; Plasma: albumin, total protein, total bilirubin, urea nitrogen, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, alkaline phosphatase, and ornithine-carbamoyl transferase)
- Urinalysis: Day 70 (examined microscopically, and tested for pH, specific gravity, occult blood, ketones, glucose, protein, bilirubin and urobilinogen)
Sacrifice and pathology:
GROSS PATHOLOGY: Yes Organs were weighed. Full pathological examinations were also made after exposure to the additives at four times the no-adverse-effect level.

HISTOPATHOLOGY: Yes Thirty-five tissues were subjected to routine histological examination
Statistics:
Not reported.
Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
decreased growth at 0.31 and 0.62 % (reduced by 16.6 and 52 %, respectively) 
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Seminal vesicles weighed approx. ½ to 1/3 of the control values.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
0.62 %:  Reduced size of the seminal vesicles; reduced number of secretory granules, tubular collapse in the prostate, and reduction of the amount of secretory materials in the prostate. No other changes were observed.
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
MORTALITY: not reported.
BODY WEIGHT:  - decreased growth at 0.31 and 0.62 % (reduced by 16.6 and 52 %, respectively) 
CLINICAL SIGNS: - not reported
ORGAN WEIGHT: Seminal vesicles weighed approx. ½ to 1/3 of the control values.
CLINICAL PATHOLOGY: - no effects reported.
PATHOLOGY:  - 0.62 %:  Reduced size of the seminal vesicles; reduced number of secretory granules, tubular collapse in the prostate, and reduction of the amount of secretory materials in the prostate. No other changes were observed.
Dose descriptor:
NOAEL
Effect level:
ca. 79 mg/kg bw/day (actual dose received)
Sex:
male
Basis for effect level:
other: see 'Remark'
Critical effects observed:
not specified

Table 1. Conversion of TMA-HCL (CAS 593 -81 -7) test concentrations to TMA (CAS 75 -50-3) doses.

TMA-HCl
conc (% in diet)

TMA-HCl (doses, mg/kg bw)

TMA (doses, mg/kg bw)

 

Calculated

Rounded to 2 Sig. Fig.

Calculated

Rounded to 2 Sig. Fig.

0

0

0

0

0

0.04

32

32

20

20

0.08

64

64

40

40

0.16

128

130

79

79

0.31

248

250

150

150

0.62

496

500

310

310

Conclusions:
Based on study results, NOAEL of 79 mg/kg bw TMA was established.
Executive summary:

In a 90-day study, male Sprague–Dawley rats received 0.04. 0.08, 0.16, 0.31, and 0.62 % trimethylamine hydrochloride in diet (corresponding to 0, 20, 40, 79, 150 and 310 mg/kg bw of trimethylamine) (Amoore et al., 1978). No mortality was reported, but decreased weight gain and organ weights was observed in the two highest dose groups (at 0.31 & 0.62 % in diet). Based on the study results, NOAEL of 0.16 % diet TMA-HCl (= 130 mg/kg bw/day TMA-HCl (rounded from 128) = 79 mg/kg bw TMA) was established.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
130 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Repeated dose toxicity: oral

In a weight of evidence study, male Sprague–Dawley rats received 0.04. 0.08, 0.16, 0.31, and 0.62 % trimethylamine hydrochloride in diet (corresponding to 0, 20, 40, 79, 150 and 310 mg/kg bw of trimethylamine) during 90 days (Amoore et al., 1978). No mortality was reported, but decreased weight gain and organ weights was observed in the two highest dose groups (at 0.31 & 0.62% in diet). Based on the study results, NOAEL of 0.16% diet TMA-HCl (= 130 mg/kg bw/day TMA-HCl (rounded from 128) = 79 mg/kg bw TMA) was established.

Justification for classification or non-classification

Classification and labelling for repeated (or prolonged) exposures is not warranted 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.