Registration Dossier

Administrative data

Description of key information

Repeated dose toxicity: Oral NOAEL (rat, m/f): = 1000 mg/kg bw/day (OECD 422)

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
1 000 mg/kg bw/day
Study duration:
subacute
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 adverse effect observed

Additional information

Justification for grouping of substances and read-across

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

 

 

Overview of repeated dose toxicity, oral

CAS No.

NOAEL [mg/kg bw/day]

63705-03-3 (a)

Target substance

subacute study (OECD 422): NOAELparental = 1000 mg/kg

subchronic study (90 -day) RA: deca-glycerol deca-oleate

Decaglycerol decaoleate (b)

subchronic study (90 -day): NOAEL = 10 % (m, f) (27,780 (m) and 28,985 (f) mg/kg bw/day)

 

(a)    Target substance subjected to registration is indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

(b)    Substances not subject to registration are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

 

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3).

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Since no subchronic study investigating the repeated dose toxicity, oral are available 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3), in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substance deca-glycerol deca-oleate.

 

Deca-glycerol deca-oleate

A 90-day oral feeding study (King, 1971) was performed with the structurally related analogue substance decaglycerol decaoleate according a method equivalent to OECD Guideline 408. Test substance was administered via diet to 20 Sprague-Dawley rats per dose group at specified dose levels (2.5, 5, and 10% corresponding to approx. 6944, 13,890 and 27,780 mg/kg bw/day for males and 7246, 14,493 and 28,985 mg/kg bw/day for females). Soyabean oil was used as the control fat. All animals appeared to be in excellent health during the duration of the study, and no adverse effects were observed with regard to survival, growth, absolute and relative organ weights, and histopathology. With regard to food consumption, it was found that males fed 10% PGE consumed more food and had a poorer feed efficiency value than male control animals. However, despite decreased feed efficiency those animals consumed enough food to maintain normal growth.

Concerning hematology and clinical chemistry the values fell within normal ranges, and there were no indications of any blood disorder. Some values were significantly different from SBO controls, however differences were usually quite small and in no case established any trend or pattern indicative of a dose-related effect. Urine collected from each animal appeared to be normal in regard to color clarity, sediment, specific gravity and pH, total nitrogen excretion during the third and ninth week by females fed PGE at the 10% level was significantly greater than the control value and appears to be related to dietary treatment, the highest nitrogen excretion (male and female) was from the animals fed the highest dose PGE, the reason for this difference is not understood but it should be recognized that other parameters, including three derived from histologic examination of the urinary tract were normal.

The only gross observation of significance was what appeared to be very mild, chronic murine pneumonia in 18% of the animals, but the affected animals were scattered throughout all the groups and the effect was not related to the feeding of PGE.

The percentage of dietary fatty acids absorbed decreased as the level of PGE in the diet was increased. In all cases fat absorption by animals fed PGE at the 5 and 10% dietary levels was significantly less than corresponding SBO control values. Absorption in animals fed the lowest dose was also less but not significantly different. Values from the group fed oleic acid and glycerol fell between those of the 5% PGE and SBO control.

Gas-liquid Chromatography analyses of fecal fatty acids showed that excretion of oleic acid increased in a dose-related fashion: the oleic acid content of fecal fatty acids from animals fed the SBO control diet was 23% compared to 32, 41 and 51% when PGE was fed at levels of 2.5, 5, and 10%. The increased excretion of fatty acids in general and oleic acid in particular shows that absorption of dietary PGE was not complete. The fecal oleic acid may have resulted from the excretion of intact PGE or from hydrolyzed or partially hydrolyzed but unabsorbed material. The oleic acid content of fecal fatty acids from animals fed free oleic and glycerol was 41% corresponding exactly to the 5% PGE group.

 

The 90-day oral NOAEL was determined to be 10% of the test substance, which refers to approximately 27,780 mg/kg bw/day for males and 28,985 mg/kg bw/day for females when administered by daily feeding to rats for 90 days.

 

There is no data available on the repeated dose toxicity after dermal application and inhalation.

Conclusions

In conclusion, the available data on repeated dose toxicity via the oral route with the substance itself and a structurally related Deca-glycerol deca-oleate showed no adverse effects in animals treated orally with the highest applicated dose.

Justification for classification or non-classification

Based on information on the substance itself and on the read-across from the structurally similar substance, the available data on oral repeated dose toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.