N-(carboxymethyl)-3-[(2Z)-docos-2-enoylamino]-N,N-dimethylpropan-1-aminium

Endpoint summary

Description of key information

Oral subacute repeated dose toxicity of DV6850 was assessed in a 28-day gavage study in the rat. Toxicity, characterised as non-glandular stomach irritative and inflammatory lesions, was noted in a single female rat at 150 mg/kg/day and in all animals at 1000 mg/kg/day. The dose level of 50 mg/kg/day was considered to be a clear No Observed Effect Level (NOEL)  for local effects on forestomach. The NOAEL for systemic effects was 150 mg/kg/day over 28 days of administration, based on bodyweight and thymic changes at the highest dose of 1000 mg/kg/day.
Oral subchronic repeated dose toxicity was also assessed on other members of the AAPB chemical category, in two distinct 90-day gavage or dietary studies in the rat. In these studies, the NOAEL for systemic effects was approximately 300 mg/kg/day over 90 days of administration, the highest dose level tested (corresponding to 1000 mg/kg/d of test solution).
The oral repeated toxicity of DV6850 was consistent with that of other members of the AAPB chemical category in terms of findings and NOAEL order of magnitude, supporting the intra-category read-across.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

NOAEL

150 mg/kg bw/day

Study duration:

subacute

Species:

rat

Additional information

The systemic toxicity of DV6850 to the rat when repeatedly administered orally for a period of 28 consecutive days was assessed in a

valid GLP study according to OECD TG 407. DV6850 was administered by oral gavage, once daily, at dosage levels of 50, 150 or 1000 mg/kg/day. Toxicity characterised as non-glandular (fore)stomach lesions were noted in a single female at 150 mg/kg/day and all animals at 1000 mg/kg/day. The dose level of 50 mg/kg/day was considered to be a clear No Observed Effect Level (NOEL) for local effects on forestomach. The NOAEL for systemic effects was 150 mg/kg/d based on bodyweight and thymic changes at the highest dose of 1000 mg/kg/d.

Forestomach gastritis is a common finding in rat gavage studies on irritative test items. This treatment related finding is generally forced by the gavage exposure regime with constantly repeated bolus ingestion, normally reversible after cessation of treatment and almost missing when the test items are applicated via food or drinking water. A forestomach or a functional correlate to the rat forestomach is missing in humans. The irritative rat forestomach gastritis is judged as not relevant in view of a potential serious health risk for humans due to significant different anatomic situation and exposure probability in humans.

The oral subchronic repeat-dose toxicity of DV6850 can also be read-across from studies on other members of the AAPB chemical category. Coco (C8 -C18) AAPB was administered to rats over 90 days by either oral gavage or dietary administration. In both 90 -day studies, the NOAEL for systemic effects was approximately 300 mg/kg./d (247 mg a.i./kg in feed and 300 mg a.i./kg by gavage). Local toxic effects (forestomach gastritis) in the 90 -day gavage study were consistent with those observed in the 28 -day study using DV6850, where irritative and inflammatory forestomach lesions were observed. Furthermore, the NOAEL order of magnitude for DV6850 administered over 28 days (150 mg/kg/d) is not inconsistent with that observed for Coco AAPB over 90 days, although higher (300 mg/kg/d) with a longer duration, based on the dose spacing in the 28 -day study and provided that the tested dose level immediately higher than 150 mg/kg was 1000 mg/kg. The actual maximal NOAEL of DV6850 administered orally over 28 days may likely have been equivalent to or higher than 300 mg/kg/d. Therefore, the oral repeated toxicity of DV6850 is consistent with that of other members of the AAPB chemical category in terms of findings and NOAEL order of magnitude, supporting the intra-category read-across.

No repeated dose toxicity data specific to DV6850 are available for the dermal and inhalative routes of exposure.

Justification for classification or non-classification

There is no evidence for intrinsic toxic properties of DV6850 relevant to humans obtained from the results of a reliable, relevant and adequate subacute oral toxicity study in rats. Therefore, no classification is required for repeated dose toxicity according to Directive 67/548/EEC or CLP, Regulation (EC) No 1272/2008 with respect to systemic toxicity or Specific Target Organ Toxicity, repeated administrations.