Trimethylamine, N-oxide

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subacute

Species:

rat

Toxicity to reproduction: other studies

Additional information

The potential toxicity of trimethylamine N‑oxide dihydrate in the rat after oral (gavage) administration was assessed including initial information on possible effects on reproduction and development and neurotoxicity.

Three test groups and one control group, each containing 10 males and 10 females were used. Males were treated for 2 weeks prior to mating, until necropsy after at least 4 weeks of treatment. Females were treated for 2 weeks prior to mating, then through mating, gestation and until the day before necropsy. Dose levels were 50, 150, and 300 mg/kg bw/day

The following parameters were evaluated in this study: mortality, clinical observations, body weights, food consumption, estrous cycles (F0 animals only), neurobehavioral evaluations, mating performance, duration of gestation, litter observations, litter survival indices, litter and pup weights, pre-weaning physical development of F1 animals, clinical pathology parameters (haematology, coagulation and clinical chemistry), TSH and T4 parameters, organ weights and macroscopic and microscopic examinations.

Administration of trimethylamine N-oxide dihydrate at 300 mg/kg bw/day in females was associated with initial body weight loss during the premating period followed by lower body weight gain and lower food consumption throughout gestation. Test item-related effects at 150 mg/kg/day in females was limited to low food consumption during the gestation period only. Recovery of body weight and food consumption effects at both dose levels was observed during the lactation period.

There were no test item-related effects on paternal toxicity, embryo-fetal development, pup development or neurobehavior.

In conclusion, administration of Trimethylamine N‑oxide dihydrate by once daily oral gavage in Han Wistar rats was associated with transient and recoverable effects on body weight and/or food consumption in females only at 150 and 300 mg/kg bw/day. No reproductive or developmental effects were observed. A reproductive and developmental NOAEL of 300 mg/kg bw/day was concluded.

Justification for classification or non-classification

Based on the results of the OECD 422 study, trimethylamine N-oxide does not meet the classification criteria of EC 1272/2008 (as ameded) for reporductive toxicity.