Trimethylamine

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: accepatable, well-documented publication, which meets basic scientific principles, see also 7.8.2

Remarks:

The route of exposure (i.p.) is not standard. beside that an acceptable, well-documented publication which meets basic scientific principles.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Devepolmental toxicity of methylamines in mice

Author:

Guest, I., Varma, D.R.

Year:

1991

Bibliographic source:

Journal of Toxicology and Environmental Health, 32:319-330, 1991

Materials and methods

Type of study / information:

Exploration if chronic administration of methylamines can cause reproductive toxicity using pregnant CD-1mice and mouse embryos in culture as experimental models.

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 414

GLP compliance:

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.

Results and discussion

Any other information on results incl. tables

A concentration related decrease of yolk-sac diameter, paleness of the yolk-sac, crown-rump length, head length, somite number and survival was seen in all treatment groups.

At 0.5 mM and above development of the forelimb and the brachial bar was retarded.
Up to 0.75 mM neuropores closed well.
Up to 1 mM heart development was unaffected.
At 1 mM only 33% of the embryos was dorsally convex.
Concentration related decreases of embryonal RNA, DNA and protein were seen.

In vitro studies: all three methylamines produced concentration-dependent decreases in yolk-sac diameter, crown-rump length, head length, and fetal survival; developmental score and somite number also exhibited a similar concentration-dependent decrease.

The effect of all the three methylamines was more marked on the head length than on crown-rump length and yolk-sac diameter.

The external appearance of embryos was not affected by low concentrations of methylamines. at higher concentrations (> 0.5 mM), there appeared to be a dispropotionate retardation in forelimb and branchial bar development relative to the development of other organs. All embryos were dorsally convex at 1 mM MMA or DMA.

The development of hearts was unaffected at concentrations up to 1 mM of all 3 methylamines and neuropores closed well up to concentrations of 0.75 mM.

All three methylamines produced concentration-dependent decreases in embryo RNA, DNA and proteins; the realtive order of toxicity was the same as in vivo, namely TMA> DMA > MMA.

- all three methylamines possess teratogenic potential in varying degrees.

Applicant's summary and conclusion

Conclusions:

At all tested concentrations teratogenic potential was demonstrated.
- The NOAEL for maternal and developmental toxicity, including teratogenicity, was 155 mg/kg bw based on the absence of any adverse findings at this dose

Executive summary:

Reproductive toxicity

In a toxicity study in mice no effect of intraperitoneal monomethylamine hydrochloride administration (from day 1 to 17 of gestation) on body weights and food consumption of the females and on organ weights were observed up to 115 mg/kg bw. From the above, it was considered that reproductive/developmental toxicity NOEL is 225.4 mg/kg bw/day for female mice. 

Developmental toxicityA study performed by Guest et al. in 1991, dealt with the investigation of maternal or fetal effects after administration of MMA via intraperitoneal injection. The number of resorbed and dead fetuses were equally distributed across all doses of MMA, and, therefore, is considered to not be treatment related.None of the amines (MMA, DMA, TMA) caused a significant increase in external, internal organ, or skeletal abnormalities, but all three possess a teratogenic potential in varying degrees.Monomethylamine did not exert any fetal effects at the highest dose level tested.In vitro, all three methylamines produced concentration-dependent decreases in yolk-sac diameter, crown-rump length, head length, and fetal survival; developmental score and somite number also exhibited a similar concentration-dependent decrease. The external appearance of the embryos was not affected by low concentrations of methylamines, but at higher concentrations (> 0,5 mM), there appeared a dispropotionate retardation in the forelimb and branchial bar development relative to the development of other organs. SoMMA inhibits development of mouse embryos in culture.