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

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

NOAElL(reproduction)>/=2000 mg/kg bw/d (rat, three generation study; RL2, non-GLP), read-across from polyglycerol polyricinoleate and Medium chain triglycerides

Link to relevant study records

Reference

Endpoint:

multi-generation reproductive toxicity

Type of information:

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

Adequacy of study:

key study

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: supporting information

Species:

rat

Sex:

male/female

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Dose descriptor:

NOAEL

Effect level:

2 000 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: no adverse effects observed

Critical effects observed:

not specified

Remarks on result:

not measured/tested

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

2 000 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: no adverse effects observed

Critical effects observed:

not specified

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

2 000 mg/kg bw/day (nominal)

Based on:

act. ingr.

Sex:

male/female

Basis for effect level:

other: no adverse effects observed

Critical effects observed:

not specified

Reproductive effects observed:

no

Conclusions:

Based on read-across from structurally related source substances Polyglycerin caprylate/caprinate is not a reproductive toxicant (NOAEL >/= 2000 mg/kg bw/d).

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2 000 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No experimental data are available for the target substance polyglycerin caprylate/caprinate. However, studies on toxicity to reproduction are available for the closely related source substances polyglycerol polyricinoleate and Medium chain triglycerides (MCT). A justification for read-across is given in iuclid section 13.

 

In the period of most rapid growth for the rats, polyglycerol polyricinoleate had no effect on the food intake during this period and had no subsequent effect on the growth of the rats.

During the three-generation study the breeding females consumed PGPR at levels of greater than 2 g/kg body weight (based on a food intake level of up to 40 g/day during lactation and the inclusion of polyglycerol polyricinoleate in the diet at the fixed level of 1.5%). At this level of polyglycerol polyricinoleate consumption the breeding performance of the treated rats was similar to those rats fed the control diet. There was no effect of polyglycerol polyricinoleate on the suckling pups receiving polyglycerol polyricinoleate from their mothers' milk.

The ingestion of polyglycerol polyricinoleate at a dietary level of 1.5% did not produce any adverse effect on reproductive capacity or development of the offspring during three generations of continuous exposure.

 

In a reproductive toxicity study, young adult male and female Wistar rats were fed a balanced diet containing 19.6% of Medium chain triglycerides (MCT) (75% caprylic and 25% capric acid) for 3 wk before mating. This group was compared to concurrent groups fed high oleo oil, butter fat or coconut oil diets. Body weight gain and litter size and birth weights of the animals on the MCT diet were similar to those of rats on the other diets. Mortality of the F1 and F2 pups during lactation was somewhat higher, and weight gain was slightly lower in the MCT diet group pups. This was directly attributed to a smaller volume of milk secreted by the dams and was supported by observations that there was considerably less body fat on these animals. After weaning, the F1 and F2 generations, which continued to be fed the MCT diet, showed a weight gain comparable to that of control rats on the other diets. There were no adverse effects on reproductive parameters or on pup development aside from slightly lower body weight gains during the lactation period.

 

The results are considered to be adequate to assess the reproductive toxicity of the target substance polyglycerin caprylate/caprinate. There are no data gaps for the endpoint toxicity to reproduction. There is no reason to believe that the results would not be relevant to humans. 

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

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