Fatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol]

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Oral (OECD 414), rat: NOAEL >= 5000 mg/kg bw/day;
Oral  (OECD 414), rabbit: NOAEL> = 1200 mg/kg bw/day

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

There are no specific reproductive toxicity studies available forFatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol] (CAS# 91050-80-5)to assess the potential to induce effects on reproduction. In accordance with Regulation (EC) No 1907/2006, Annex IX, 8.7.3, column 1, a two-Generation Reproduction Toxicity Study does not need to be conducted as the results of a 28-day or 90-day repeated dose toxicity study do not demonstrate any adverse effects on reproductive organs or tissues.

In the 13-week oral repeated-dose toxicity study in rats,deca-glycerol deca-oleatereproductive organs were examined.

  

Deca-glycerol deca-oleate

In 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 reproductive organs were examinated as well. 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, 13890 and 27780 mg/kg bw/day for males and 7246, 14493 and 28985 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 special regard to the reproductive, the examination of organ weights as well as gross and histo-pathology revealed to substance-related findings.

The 90-day oral NOAEL was determined to be 10% test substance, which refers to approximately 27780 mg/kg bw/day for males and 28985 mg/kg bw/day for females when administered by daily feeding to rats for 90 days.

 

In addition, the prenatal developmental toxicity studies withMedium/Long Chain Triglycerides (MCT/LCT)using rats and rabbits did not show any toxic effects on development and resulted in a NOAEL > 1000 mg/kg bw effects on development. Therefore, theFatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol]was not considered to have a potential for develomental toxicity

 

In conclusion, according to Regulation (EC) No 1907/2006 and with respect to animal welfare, further reproductive toxicity studies would be scientifically unjustified.

 

Conclusion for reproductive toxicity

No reproductive toxicity studies are available forFatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol] (CAS# 91050-80-5). However in one 90-day study with structural related analogue substance Decaglycerol-decaoleate showed no indications for effects on reproductive organs As no indications for effects on reproductive organs were found (NOAEL was approximately 27780 mg/kg bw/day for males and 28985 mg/kg bw/day for females) Fatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol]) was not considered to have toxic effects on reproductive organs.

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

Toxicity to reproduction: other studies

Additional information

Justification for grouping of substances and read-across

There are no data available for developmental toxicity of Fatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol] (CAS# 91050-80-5).In order to fulfil the standard information requirements set out in Annex VIII, 8.7.1 and Annex XI, 8.7.2, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

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 for developmental toxicity

CAS	NOAEL [mg/kg bw/day]
91050-80-5 (a) Target substance	RA: Medium/Long Chain Triglycerides
Medium/Long Chain Triglycerides (MCT/LCT) (b)	≥1000

(a) Substances subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

 

 

The above mentioned substance is 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 fatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol] (CAS# 91050-80-5).

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

 

Discussion

Developmental toxicity

Since no studies investigating the developmental toxicity of fatty acids, C16-18, tetraesters with 3,3'-oxybis[1,2-propanediol] (CAS# 91050-80-5) are available, in accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substanceMedium/Long Chain Triglycerides (MCT/LCT)was conducted.

 

 

Medium/Long Chain Triglycerides (MCT/LCT)

In a prenatal developmental toxicity study similar to OECD Guideline 414, the effects of medium Chain Triglycerides (MCT) on female Crl:CD BR rats were investigated during Days 6 to 15 of gestation (Henwood, 1997). The animals (25 or 29 for the low and high dose, respectively) received the test substance in 20% emulsion containing a 3:1 ratio of MCT:LCT (Long Chain Triglycerides) at doses of 1000 and 4280 mg/kg bw/d by intravenous infusion via the caudal vein for a 4-h period per day. A control group of 25 animals received 0.9% saline. On Day 20 of gestation, dams were sacrificed and maternal as well as foetal examinations were performed. At 4280 mg/kg bw/day, maternal toxicity occurred and involved the increased incidence of necropsy findings on the tail, which were considered to be due to extravasation of the MCT:LCT lipid test article into perivascular areas. In addition to tail effects, there was a trend toward an increasing incidence of necropsy findings in the high-dose group, including enlarged lymph nodes, enlarged spleen, hydronephrosis/enlarged renal pelvis, small thymus, and small red lung foci. There were no significant group differences in pre-implantation or post-implantation loss or in the mean percentage of live or resorbed foetuses in treated animals. No dead foetuses were found and the mean foetal sex ratios and the mean foetal body weight of the treated animals were comparable to those of controls. No test substance-related external, soft tissue, or skeletal malformations were noted in the exposed foetuses. Based on the results of the study, the NOAEL for developmental toxicity in male and female Crl:CD BR rats was established at 4280 mg/kg bw/day.

 

In the same study, 15 female Hra:(NZW)SPF rabbits were treated daily with MCT (Medium Chain Triglycerides) by a 5h intravenous infusion via a marginal ear vein at doses of 1000 and 4280 mg/kg bw/day from gestation day 6 through 19 (Henwood, 1997). A similar constituted control group was injected with 0.9% saline. In dams, administration of the test substance resulted in lower maternal food consumption and significant body weight loss during treatment at 4280 mg/kg bw/day. All pregnant animals had at least one viable foetus at scheduled caesarean section on GD 29. The observed foetal effects (i.e., increased resorptions, decreased foetal body weights, and increased incidence of morphological anomalies) were assumed to be the result of dietary deprivation, maternal toxicity, or both, rather than a direct teratogenic effect of the test article. Based on these results, the NOAEL for developmental toxicity was set at 1000 mg/kg bw /day in rabbits.

 

In summary the reliable studies showed no treatment-related effects on maternal and developmental toxicity.

Justification for classification or non-classification

Based on read-across from structurally similar substances, the available data on developmental 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.