Fatty acids, C16-18 and C18-unsatd., compds. with triethanolamine

Endpoint summary

Description of key information

When the physicochemical properties of 'Fatty acids, C16-18 and C18-unsatd., compds. with triethanolamine’  were assessed for toxicokinetic properties, absorption from the gastro-intestinal tract was considered to be limited, however taking into account possible dissociation a higher absorption of various fractions was considered to be possible. Respiratory deposition and absorption as well as dermal absorption were assessed to be limited to very low, respectively. The latter was confirmed by calculation of the dermal flux, which was 0.093 µg/cm2.h.

Distribution in the body is expected to be limited, unless dissociated fragments are absorbed which are then rapidly distributed, metabolised and eliminated.

Limited data were available for estimation of metabolism, however based on biodegradation studies the substance was indicated to be readily biodegradable, and if dissociated, fragments are rapidly eliminated from the body.  Bioaccumulation is not expected.Finally, several routes of excretion (e.g. urine, saliva, sweat, breast milk) were assessed to be possible, based on the physicochemical properties.  

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

90

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

30

Additional information

According to chapter R.7C (p145 …) of the endpoint specific guidance of REACH, physicochemical data may be used for a qualitative TK assessment. The data below were used for a qualitative toxicokinetic assessment.

 

SUMMARY

Absorption of ‘Fatty acids, C16-18 and C18-unsatd., compds. with triethanolamine’ was assessed as follows based on physicochemical/toxicological data following ECHA guidance 7c (ECHA Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance, November 2012 Version 1.1). Other data were based on specific study reports and literature references.

-Absorption

The substance is an UVCB consisting mainly (50-98%) of C18:1 chains. It is a tertiary amine salt resulting from neutralisation of triethanolamine by commercially available oleic fatty acids at room temperature and pressure. The compound is a viscous waxy paste with a molecular weight ranging from 403.7 g/mol to 433.8 for the C16:1 to C18 chains. The water solubility is low (approximately 10 mg/L). The LogPow is around 4.86. The vapour pressure is < 550 Pa.

-Oral/GI absorption:

Because of the very high logPow (>4) and the very low water solubility (ca. 10 mg/L), oral absorption might be expected to be rather limited. From the acute oral toxicity study in rats dosed at 2000 mg/kg bw, no toxic effects were observed. However in the repeated dose toxicity study, some clinical observations were observed and oral absorption was considered to be possible but limited.

Note:  As the registered substance is a salt of triethanolamine with oleic acids, absorption was compared with dietary triglycerides (glycerol esterified to fatty acids), which are common in the food and triethanolamine. From literature, it is known that triglyceride absorption is high due to gastro-intestinal lipase hydrolytic activity and micellular solubilisation, followed by intracellular reconstitution of triglycerdies and packaging in cellular chylomicrons. Taking into account dissociation of the registered substance to triethanolamine and fatty acids, absorption is considered to be possible, with interaction to normal fat absorption taking place. From absorption studies in animals, it was seen that triethanolamine may be absorbed in the gastrointestinal tract. Absorption was detected by examining the urine and feces of rats and mice. After oral application in rats, rapid absorption was observed and excretion occurred mainly in the urine. 24 hours after dosing, 53% was recovered in the urine and 20 % in the feces.

Conclusion:    From a conservative viewpoint, therefore 90% absorption rate is proposed.

-Respiratory absorption:

Because the substance is a viscous waxy paste with a low vapour pressure (<550 Pa)inhalation and/or deposition of the substance seems unlikely. Therefore the respiratory absorption will be limited. Once it is deposited, it can theoretically be absorbed directly across the respiratory tract epithelium because of the high logPow. However, this route of exposure is theoretical.

Conclusion:    From a conservative viewpoint, 30% absorption rate is proposed.

-Dermal absorption:

The stratum corneum provides its greatest barrier function against hydrophilic compounds, whereas the viable epidermis is most resistant to penetration by highly lipophilic compounds. Due to the logPow of above 4, it is expected that uptake in the stratum corneum will be high, however the transfer between the stratum corneum and the epidermis will be limited due to the low water solubility. Furthermore the rather high molecular weight, the absence of acute dermal toxicity and the fact that the substance does not show skin irritation will further limit dermal absorption. Dermal penetration constant (Kp), was calculated to be 9.3 x 10^-3cm/h, whereas maximum dermal flux is 0.093 µg/cm²x h Therefore dermal absorption is concluded to be theoretically possible but very limited.

Note:  If dissociation is taking place, the metabolism and accumulation potential of the oleic fatty acid fragments and triethanolamine have to be taken into account separately. From absorption studies in animals, it was seen that triethanolamine may be absorbed through the skin. Absorption was detected by examining the urine and feces of rats and mice. After dermal application in mice, 60% was recovered from the urine, 20 % from the feces; less than 10% was detected in the skin at the site of application.

Conclusion: From a conservative viewpoint, 10% absorption rate is proposed.

 

For the assessment ofdistribution, metabolism and excretionphysicochemical and toxicological properties are also taken into account according to ECHA guidance 7c(ECHA Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance, November 2012 Version 1.1).

-Distribution:

Because of the high LogPow (>4) distribution into cells is possible. However the very low water solubility together with the molecular weight of above 400 g/mol will limit the distribution. Furthermore since no signs of toxicity are observed after oral dosing with 2000 mg/kg bw, distribution is expected to be low. Note: If dissociation is taking place, triethanolamine distribution is known to be low since from radioactivity studies in mice (iv and dermal application) it is seen that only low amounts (≤ 6%) are distributed in the body.

-Metabolism & Accumulation potential:

Oleic acid will be rapidly digested. Since it is a long chain-fatty acid it will be re-esterified to triacylglycerols and either metabolized for energy or stored in adipose tissue. Based on the lipophilicity of the substance, the substance is not expected to accumulate in the lung. Based on the high logPow the accumulation in adipose tissues and stratum corneum is expected to occur. The substance can persist in the stratum corneum, but will eventually be cleared as the stratum corneum is sloughed off. Regarding bioacummulation potential, studies for readily biodegradation both in normal water and marine water indicate that there is a potential for ready biodegradability. Therefore bioaccumulation is not expected.

Note:  If dissociation is taking place, dermal absorption of triethanolamine in mice was measured to be more than 95%. The serum half-life was approximately 9.5 hours after either a 1 mg/kg intravenous injection or a 1000 mg/kg dermal application.

-Excretion:

Excretion in the urine is not expected because of the low water solubility. Because of the high logPow excretion in bile, breast milk, saliva/sweat and excretion by exfoliation might be expected. As the substance has a low vapour pressure, exhalation is not expected.

Note:  If dissociation is taking place, it can be assumed that the oleic fatty acid fragments will be utilized in the fat metabolism, whereas trietholamine will be excreted easily in the urine.

 

References

Ji, Y., Li, X. and Tso P. Intestinal Fatty acid Absorption.Immun., Endoc. & Metab. Agents in Med.Chem., 2009, 9, 60-73.

 

NTP Technical report on the toxicology and carcinogenesis studies of triethanolamine in F344/N rats and B6C3F1 mice., National Toxicology program, U.S. Department of health and human services, NIH Publication No. 00-3365, November 1999

 

Kroes R, Renwick AG,*, Feron V, Galli CL, Gibney M, Greim H,Guy RH, Lhuguenot JC, van de Sandt JJM. Application of the threshold of toxicological concern (TTC) to the safety evaluation of cosmetic ingredients. Food and Chemical Toxicology 45 (2007) 2533–2562

 

Stott WT, Waechter JM, Rick DL, Mendrala AL. Absorption, distribution, metabolism and excretion of intravenously and dermally administered triethanolamine in mice, Food and Chemical Toxicology 38 (2000) 1043-1051

 

[Trade name] Component test for biodegradability. Report RF-97/151. Rogaland Research.

[Trade name] Component test for biodegradability. Report RF-19997/071. Rogaland Research.