Cyclohexane, oxidized, aq. ext.

Endpoint summary

Description of key information

Cyclohexane, oxidized, aquous extract components are expected to be readily absorbed after oral administration, partially metabolized to various metabolites, including additional adipic acid and CO2 which are excreted via urine and breath, respectively.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Cyclohexane, oxidized, aqueous extract (COP Acid; CAS No. 68915-38-8) is an aqueous mixture of monocarboxylic acids, dicarboxylic acids and water. There are only two major components, other than water; specifically they are adipic acid (CAS# 124-04-9) and 6-Hydroxyhexanoic Acid (CAS# 1191-25-9). The remaining minor components are other monocarboxylic acids and dicarboxylic acids that are structurally related either as intermediary metabolites or as combinatory fragments that are ultimately metabolized to CO2 or excreted in the urine, much the same as Adipic acid. Furthermore, the other major component, 6-Hydroxhexanoic acid, is metabolized to Adipic acid during normal mammalian oxidative metabolism. With regards to the minor components, glutaric acid, a normal degradant of amino acid metabolism, is known to form as a metabolite from ketoadipic acids and is metabolized like many short-chain fatty acids. Succinic acid, an intermediary metabolite of many processes, including fatty acid metabolism, is known to feed into the Krebs process to produce CO2. Formic acid, a one-carbon metabolite of fatty acid degradation and other metabolic processes, also results in either elimination as parent compound or as CO2. 5-Hydroxyvalerate is metabolized to glutaric acid, above. 5-Carboxypentyl 6-hydroxyhexanoate forms from the joining of 6-hydroxhexanoic acid with 5-hydroxyvalerate and is believed to be metabolized back to its parent structures before being processed further. 3-hydroxyadipic acid, 3,6-lactone is a known metabolite of many dicarboxylic acids and is eliminated in the urine or as CO2.

 

Information on Read Across Substance (Adipic Acid):

 

Non-human information:

 

Hazards identified by OECD/ICCA high production volume chemicals program in 2004:

 

"After oral administration by gavage of radioactive adipic acid to fasted rats up to 70 % of the dose was exhaled as CO2. In the urine the parent compound adipic acid and metabolic products identified as urea, glutamic acid, lactic acid, beta-ketoadipic acid and citric acid were found (percentages not specified). Adipic acid was metabolized by beta-oxidation in a similar fashion as fatty acids and acetate was a metabolite of adipic acid. Radioactive glycogen was isolated in experiments where glycogen formation in the liver was encouraged by oral administration of glucose together with radioactive adipic acid (Rusoff et al. 1960). When adipic acid or its sodium salt was administered to non fasted rats, rabbits and one dog 18 – 71 % of the doses were excreted in the urine. Breath was not analyzed in these studies (Mori 1918; Bernhard and Andreae 1937; Enders 1941). In an oral 28-day subacute study in rats excretion of adipic acid was similar from day 1 to 28, indicating that adipic acid did not accumulate during the treatment. Breath was not analyzed, (Enders 1941). It is unclear whether the methods of detection in these early studies were reliable. "

 

Human information:

 

Hazards identified by OECD/ICCA high production volume chemicals program in 2004:

 

"Adipic acid was orally administered to humans to investigate compound excretion. The highest dose administered in one volunteer was 70 g over 10 days. 3 other persons took 19 to 23.4 g over up to 9 days. 15 - 75 % of the adipic acid dose was found unchanged in the urine after oral administration of up to 7 g of adipic acid over up to 10 days to 7 volunteers. Breath was not analyzed, and it is unclear whether the methods of detection used were reliable (Weitzel 1942 and 1947). "

 

Updated relevant information:

None