Reaction products of amines, dicoco alkyl and glycollic acid

Endpoint summary

Additional information

Toxicokinetic assessment of the substance

 

The toxicokinetic profile of the substance was not determined by actual absorption, distribution, metabolism or excretion measurements. Rather, the physical chemical properties of the new substance, the data obtained from acute and repeated-dose toxicity studies, as well as information gained from genotoxicity assays are used to create a predicted model of toxicokinetic behavior.

 

The substance is a N, N-didodecylglycolamide with an average molecular weight of 448 gm/mol. The new substance is poorly water soluble (<1.6 x 10^-3gm/L), with a relative high octanol/water partition coefficient (log K_o/w> 6), and a very low vapor pressure (2.3 x 10^-8Pa @ 25^oC).

 

Absorption

 

The physical chemical properties highlighted above suggest that the substance

is of adequate molecular size to participate in endogenous absorption mechanisms within the mammalian gastrointestinal tract should that material be ingested. Being highly lipophilic (log K_o/w> 6), the substance is expected to readily across gastrointestinal epithelial barriers, and may also participate in micellar transport into the hepatic portal system along with other lipophilic substances (e.g., dietary fats). Yet, acute and repeated-dose oral gavage toxicity studies identified little evidence of toxicity (LD50 > 2000 mg/kg and NOEL = 1000 mg/kg/day, respectively). The lack of adverse findings following oral dosing may be due to limited gastrointestinal absorption of the test material after dosing, or a very low index of inherent toxicity for this substance, and/or its metabolite(s).

 

The substance was also tested for acute toxicity following dermal application. Once again, single-dose dermal application of the test material resulted in no manifestations of systemic toxicity that would suggest systemic absorption through cutaneous barriers.

 

The potential for inhalation toxicity was not measured for this new chemical notification. However, the substance vapor pressure indicates a very low propensity to enter atmospheric air in a respirable form. Thus, respiratory absorption under normal use and handling of this material is expected to be inconsequential.

 

Distribution

 

Systemic distribution of the substance can be predicted from the physical chemical properties of this substance. The relatively high log K_o/wand poor water solubility suggests that this substance, upon systemic absorption, may be transported through the circulatory system in association with a carrier molecule such as a lipoprotein or other macromolecule. The lipophilic character and molecular size of the substance suggests that the molecule will readily traverse cellular barriers and potentially distribute into fatty tissues. There is no evidence from repeated dose studies of cumulative toxicity as would be manifested by an accumulation of the substance or metabolites in tissues. 

 

Metabolism

 

The substance (N,N-dicoco-alkyl-2-hydroxyacetamide) contains a terminal hydroxyl group, a carbonyl and a tertiary amide group. These types of moieties are recognized to undergo phase I oxidation/reduction and subsequent Phase II conjugation. Acute and repeated-dose toxicity testing provided no evidence that The substance is being transformed to toxic metabolites. Data from mutagenicity and chromosomal aberration testing in which the substance was subjected to phenobarbitone-induced rat hepatic microsomal enzyme systems revealed no evidence of genotoxic activity, suggesting that the metabolic by-products are relatively innocuous. It is possible that the substance undergoes cutaneous metabolic transformation as well.

 

Excretion

 

The structural characteristics of the substance suggest that this molecule will readily undergo phase I and phase II metabolic transformation. The resulting metabolic by-products are expected to undergo routine renal and or biliary excretion.