Reaction products of decanoic acid and lauric acid with glycerol and polyglycerol

Endpoint summary

Description of key information

subchronic NOAEL >/= 950 mg/kg bw/d (rat; similar to OECD TG 408; RL2, non-GLP) based on the observed decreased total fat absorption at a diet containing 5 and 10% decaglycerol decaoleate

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar physicochemical, ecotoxicological and toxicological properties because
• they are manufactured from similar or identical precursors under similar conditions
• they share structural similarities with common functional groups: the target and source substances are esterification products of fatty acids of varying chain lengths with glycerol and/or polyglycerol.
• the metabolism pathway leads to comparable products (glycerol and/or polyglycerol and medium or long chain fatty acids).

Therefore, read-across from the existing toxicity studies on the source substances is considered as an appropriate adaptation to the standard information requirements of REACH regulation

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see “Justification for read-across” attached to IUCLID section 13

3. ANALOGUE APPROACH JUSTIFICATION
see “Justification for read-across” attached to IUCLID section 13

4. DATA MATRIX
see “Justification for read-across” attached to IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Reason / purpose for cross-reference:

read-across source

GLP compliance:

no

Duration of treatment / exposure:

13 weeks

Frequency of treatment:

continuously

Dose descriptor:

NOEL

Effect level:

ca. 950 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male

Basis for effect level:

other: decreased total fat absorption at 5 and 10%

Remarks on result:

other: 2.5% in diet

Dose descriptor:

NOEL

Effect level:

1 300 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

female

Basis for effect level:

other: decreased total fat absorption at 5 and 10%

Remarks on result:

other: 2.5% in diet

Critical effects observed:

no

Conclusions:

Based on read-across from structurally related source substances, the subchronic NOAEL of polyglycerin caprylate/caprinate is at least 2.5% in teh diet (corresponding to ca 950 mg/kg bw/d in males and 1300 mg/kg bw/d in females).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

950 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

No experimental data are available for the target substance polyglycerin caprylate/caprinate. However, repeated dose toxicity studies are available for the closely related source substances Medium chain triglycerides, decaglycerol decaoleate and polyglycerol polyricinoleate. A justification for read-across is given in iuclid section 13.

 

Male and female beagle dogs were fed 91 days a diet containing Medium chain triglycerides at levels of 5%, 10%, and 15% MCT added to conventional feed. Based on examination of clinical signs, body weight measurements, food consumption level, physical examinations, hematology and serum chemistry, ophthalmic examinations, and urinalysis the NOAEL for Medium chain triglycerides was found to be 15%, which was calculated to be approximately 3750 mg/kg bw/day.

 

Polyglycerol ester (decaglycerol decaoleate) was fed to rats at dietary levels of 2.5, 5.0, and 10 % for 90 days. All animals appeared to be in excellent health throughout the study, and no adverse effects were found upon survival, growth, organ weights, organ : body weight ratios, and hematologic values. There were no significant gross or microscopic tissue changes which could be attributed to dietary treatment.

Total fat absorption, as measured by fecal fatty acids, decreasedin a dose-related response. This resulted in a decreased utilization of feed by males fed PGE at the 10 % dietary level. These data show that absorption of PGE was not complete.

Excretion of nitrogen in the urine by females fed PGE at the 10% dietary level was significantly greater than the control value during both the third and ninth collection periods. The reason for this difference is not understood at the time of this study.

 

The carcinogenic potential of the food emulsifier polyglycerol polyricinoleate (PGPR) was evaluated in rats and mice. Groups of 60 male and 60 female rats were given purified diets containing 5% of either PGPR or groundnut oil for 2 years. Groups of 25 male and 25 female mice were given purified diets containing 5% of either PGPR or groundnut oil for 80 weeks. No carcinogenic effect of PGPR was observed. In addition, dietary PGPR had no adverse effect on growth, food consumption, longevity and haematology. Organ weight analysis revealed an increase in liver and kidney weight in both male and female rats and female mice. Histological analysis of tissues revealed no treatment related adverse effects.

In the rat study PGPR had no adverse effect on growth, food consumption, survival, haematology and histological appearance of tissues. The changes in weight of liver and kidneys in PGPR-fed animals was consistent with those seen in previous studies and considered to be a result of metabolic compensation in response to the high level of PGPR ingested.

Enlargement of the liver without liver cell damage can be caused by a variety of chemicals, many of which are metabolized by the liver. Most of these chemicals have also cause an increase in the metabolizing capacity of the enzyme systems associated with the endoplasmic reticulum of liver parenchymal cells.

In the mouse study PGPR had no adverse effect on growth, food consumption, survival, haematology and histological appearance of the tissues. No adverse effect on organ weights was observed except that livers and kidneys were heavier in female mice fed PGPR.

 

Caprenin, a randomized triglyceride primarily comprising caprylic (C8:0), capric (C10:0), and behenic (C22:0) acids, was administered in a semi-purified diet to weanling Sprague-Dawley rats (25/sex/group) at dose levels of 5.23, 10.23 or 15.00% (w/w) for 91 days. Corn oil was added at 8.96, 5.91 and 3.00%, respectively, to provide essential fatty acids and digestible fat calories. Corn oil alone

(12.14%) and a blend of medium-chain triglyceride (MCT) oil plus corn oil (11.21 and 3.13%, respectively) served as controls. All diets were formulated to provide about 4000 kcal/kg of diet and 26.8% of digestible calories from fat by assuming that corn oil, MCT oil, and caprenin provided 9, 7 and 5 kcal/g, respectively. Survival, clinical signs, body weight, feed consumption, feed efficiency, organ weights, organ-to-body-weight ratios, organ-to-brain-weight ratios, haematological values and clinical chemistry parameters were evaluated in all groups. Histopathology of a full complement of tissues was evaluated in the corn oil and MCT oil control groups as well as the high-dose caprenin group.

Additional rats (n = 5/sex/group) were included in the study to determine whether there was marked storage of C22:0 in heart, liver or perirenal fat at the end of the 91-day feeding period. No significant differences in body weight gain were measured with the balanced caloric diets, although feed conversion efficiency was reduced in the high-dose caprenin group. No adverse effects from the ingestion of caprenin were detected, nor were significant amounts of C22:0 present in the fat extracted from the selected fat depot sites. These results establish a no-observable-adverse-effect level (NOAEL) of more than 15% (w/w) caprenin in the diet (or more than 83% of total dietary fat), which is equal to a mean exposure level of more than 13.2 g/kg/day for male rats and more than 14.6 g/kg/day for female rats.

 

The results are considered to be adequate to assess the repeated dose toxicity of the target substance polyglycerin caprylate/caprinate.

The overall subchronic NOAEL for polyglycerin caprylate/caprinate is in excess ofapprox. 950 mg/kg bw/d in males and 1300 mg/kg bw/d in females based on the observed decreased total fat absorption at 5 and 10% decaglycerol decaoleate.

 

There are no data gaps for the endpoint repeated dose toxicity. There is no reason to believe that the results would not be relevant to humans.  

Justification for classification or non-classification

Based on the available data, polyglycerin caprylate/caprinate does not need to be classified for specific target organ toxicity after repeated exposure according to regulation (EC) 1272/2008. Thus, no labelling is required.