Glycerides, C16-18 mono-, di- and tri-, hydrogenated, citrates, potassium salts

Endpoint summary

Description of key information

Studies on oral repeated dose toxicity were available for castor oil, medium-chain triglyceride mixtures, and acetoglycerides. 
All available studies resulted in oral NOAELs of 1000 mg/kg bw/d or greater than 1000 mg/kg bw/d.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

5 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The available studies on oral repeated dose toxicity support the view that Fatty Acid Glycerides are inherently harmless, non-toxic substances; and this applies also for mixed fatty acid, and citroglycerides.

Citric acid esters of mono- and diglycerides are current EU approved food additives (= E 472c), and have been considered by the Scientific Committee on Food (SCF) on several occasions. In 1978, the SCF endorsed the “ADI not specified” for citric acid esters of mono- and diglycerides allocated by the Joint FAO/WHO Expert Committee on Food Additives (WHO, 1974; SCF, 1978). Subsequently, the Committee considered the use of E 472c was acceptable in weaning foods in biscuits, cereal-based and baby foods (SCF, 1990). In 1997, the SCF concluded that the use of E 472c was acceptable in products for infants and young children and in foods for special medical purposes (FSMPs) (SCF, 1998). This advice was implemented in Directive 95/2/EC as amended by Directive 98/72/EC and extended in 2002 (Opinion of the SCF on Citric acid esters of mono- and diglyglycerides (E472c): request for additional uses in foods for special medical purposes for infants and young children).

In addition, Glycerol stearate; Glycerides, C 16-18 and C 18 –unsaturated; Glycerides, tallow mono-, di- and tri-, hydrogenated; and Glycerides, C 16-18 and C 18 -unsaturated, mono- and di- are listed on Annex IV to REACH as causing minimum risk because of their intrinsic properties:

Subchronic repeated dose toxicity oral:

A 90 day oral feeding study with Castor oil (CAS No. 8001-79-4) was performed equivalent to OECD Guideline 408 in F344/N rats and B6C3F1 mice (Irwin, NTP report 1992). The test substance was mixed at concentrations of 0, 0.62, 1.25, 2.50, 5.00, 10.0 % (w/w) to the diet and the animals were fed ad libitum for 13 weeks. 10 animals per sex and per dose were used. The highest dose was equivalent to approx. 5.7 g/kg/day for rats and approx. 15 g/kg/day for mice. Exposure to castor oil at dietary concentrations as high as 10% in 13-week studies did not affect survival or body weight gains of rats or mice. There were no biologically significant effects noted in hematologic analyses in rats. Mild increases in total bile acids and in serum alkaline phosphatase were noted at various times during the studies in rats receiving the higher dietary concentrations of castor oil. Liver weights were increased in male rats receiving the 10% dietary concentration and in male and female mice receiving diets containing 5% or 10% castor oil. However, there were no histopathologic lesions associated with these liver changes, nor were there any compound-related morphologic changes in any organ in rats or mice. No significant changes were noted in a screening for male reproductive endpoints, including sperm count and motility, and no changes were observed in the length of oestrous cycles of rats or mice given diets containing castor oil. Thus, no significant adverse effects of castor oil administration were noted in these studies. A NOAEL of 5000 mg/kg bw/day for rats and a NOAEL of 15000 mg/kg bw/day for mice could be identified.

A 90 day oral feeding study with medium chain triglycerides was performed similar to OECD Guideline 409 in adult beagle dogs (Matulka, 2009). The medium chain triglycerides (MCTs) were comprised of a glycerol backbone esterified to medium chain length (8–12 carbon) fatty acids (FA) and, were all saturated FA. All dogs received on 91 consecutive days approximately 200 g of conventional feed with 0%, 5%, 10%, or 15% MCT for a three hour feeding regimen (4 animals per dose). Based on examination of clinical signs, body weight measurements, food consumption level, physical examinations, haematology and serum chemistry, ophthalmic examinations, and urinalysis the NOAEL for medium chain triglycerides was found to be greater than 15 % , which was calculated to be approximately 3750 mg/kg/day.

A 56 day oral feeding study with medium- and long-chain triglycerides was performed in Wistar rats (Matsuo, 2004). The effects of structured medium- and long-chain triacylglycerols (MLCT) in diets containing 50, 100, 150 or 200 g test substance/kg bw on body fat accumulation were compared with those of long-chain triacylglycerols (LCT). The diets were fed to groups of 6 young adult male Wistar rats for 56 days. Based on clinical observations, body weight, food efficiency, liver weights and clinical serum chemistry the NOAEL for rats was found to be 20 g/kg bw.

Repeated dose toxicity inhalation:

Repeated dose toxicity inhalation studies were not available. For the following reasons the inhalation route was judged to be of minor relevance:

For waxy solid fatty acid glycerides inhalation exposure seems very unlikely. Fatty acid glycerides with melting temperatures above 55ºC may be turned into powder using conventional spray-cooling technology. The particle size of powdered fatty acid glycerides is not a function of chemical composition, but is determined by the spray-cooling conditions. For the majority of industrial applications powders with mean particle size (D(0.5)) above 150µm are preferred. For a mean particle size above 150µm the proportion of respirable dust (particle size below 10µm) is negligible.

In addition, fatty acid glycerides are not corrosive and are readily hydrolysed in the body by ubiquitously expressed lipases. The likelihood of persistence in the lungs is considered to be negligible.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
GLP guideline study with castor oil

Justification for classification or non-classification

According to DSD (67/548/EEC) or CLP (1272/2008/EC) classification criteria for repeated dose toxicity, no classification is required.