Glycerides, mixed C8-10 and succinyl

Endpoint summary

Description of key information

Oral LD50 > 5000 mg/kg bw

Dermal LD50 > 5000 mg/kg bw

Inhalation: LC50 > 1.86 mg/L air (maximum attainable concentration of respirable particles; based on read-across from Glycerides, mixed decanoyl and octanoyl)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from a reference substance with similar structure and intrinsic properties. Read-across is justified based on structural similarity between the source and target substances, sharing common functional groups (esters of glycerol with carboxylic acids), common precursors and breakdown products (glycerol, fatty acids) and similarities in toxicological properties (overall low toxicity). Refer to endpoint discussion for further details.
The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

There is only one study available.

Additional information

Justification for grouping of substances and read-across

There are no data available on the acute toxicity by inhalation of Glycerides, mixed C8-C10 and succinyl (CAS 91744-56-8). In order to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from a structurally related substance is 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 physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, Glycerides, mixed decanoyl and octanoyl (73398-61-5) is selected as reference substance for assessment of the acute toxicity by inhalation of Glycerides, mixed C8-C10 and succinyl.

The read-across is based on structural similarity between the source and target substances, as the substance Glycerides, mixed C8-C10 and succinyl is composed of esters of glycerol with succinic acid and fatty acids with carbon chain lengths of C8 and C10. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Overview of acute toxicity

CAS#	91744-56-8 (a)	73398-61-5 (b)
Chemical name	Glycerides, mixed C8-C10 and succinyl	Glycerides, mixed decanoyl and octanoyl
Molecular weight (range)	470.68-1211.64	470.69-554.85
Acute toxicity: oral	Experimental result: LD50 > 5045 mg/kg bw	Experimental result: LD50 23625 mg/kg bw
Acute toxicity: inhalation	RA: CAS 73398-61-5	Experimental result: LC50 > 1.86 mg/L air
Acute toxicity: dermal	Experimental result: LD50 > 5045 mg/kg bw	--

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

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

 

Oral

Two acute oral toxicity studies were conducted with Glycerides, mixed C8-C10 and succinyl following a method similar to OECD guideline 401 (Consultox Laboratories Ltd., 1979). Groups of rats and mice (5 per sex) received single oral doses of the undiluted test material at 5 mL/kg bw, corresponding to 5045 mg/kg bw/day based on a density of 1009 mg/cm³ (Spilker, 2011). Both in rats and mice, no mortality occurred, no effect on body weight and no clinical signs of toxicity were observed up to the end of the 14-day observation period. The oral LD50 in male and female rats and mice was thus estimated to be greater than 5045 mg/kg bw (5 mL/kg bw).

In another study, a group of 5 male mice were given Glycerides, mixed C8-C10 and succinyl at 5000 mg/kg bw by oral gavage (Dufour, 1992). No mortality occurred, no effect on body weight and no clinical signs of toxicity or behavioural changes were observed up to the end of the 6-day observation period. The oral LD50 in a male mice was therefore estimated to be greater than 5000 mg/kg bw.

Inhalation

CAS No. 73398-61-5

The acute inhalation toxicity of Triglycerides, mixed decanoyl and octanoyl was studied in rats according to OECD guideline 403 and in compliance with GLP (Reminghaus, 1976). Agroup of 10 male rats was exposed to a calculated concentration of 28.1 µL/L air for 6 h using a nose only exposure system. The measured respirable test substance concentration was 1.97 µl/L (particles with a diameter below 10 µm) corresponding to an atmosphere concentration of the test aerosol of 1.86 mg/L. This was considered the maximum attainable concentration of respirable particles. 10 male control animals were sham-exposed. No mortality and no clinical signs of toxicity were observed in any of the animals during exposure and the 14-day observation period. Body weight gain was not affected during the study. At necropsy, no abnormalities were noted. Microscopic examination did not reveal any abnormal findings in lungs or tracheae and no deposits of the oily test substance in the respiratory tissues were detected. Based on these results, the LC50 value for male rats is > 1.86 mg/L.

A further GLP-compliant study was performed according to OECD guideline 403 to investigate the acute inhalation toxicity of the test substance in guinea pigs (Reminghaus, 1976). Using a nose only exposure system, the animals were exposed to the test aerosol at 1.86 mg/mL for 6 h (maximum attainable concentration of respirable particles with a diameter below 10 µm). No mortality occurred during the study period. No clinical signs of toxicity and no effects on body weight development were noted. Gross pathology did not reveal any abnormal findings. At histopathological examination, no abnormal findings in lungs or tracheae and no deposits of the oily test substance in the respiratory tissues were detected. Therefore, the LC50 value for male guinea pigs is considered to be > 1.86 mg/L.

Dermal

An acute dermal toxicity study was performed with Glycerides, mixed C8-C10 and succinyl with a protocol similar to that of OECD guideline 402 (Consultox Laboratories Ltd., 1979). Five male and five female rats were dermally exposed to the undiluted test substance at 5 mL/kg bw (5045 mg/kg bw) for 24 h under occlusive conditions. Following exposure and up to the end of the 14-day observation period, no mortality occurred and no clinical signs or changes in body weight were observed. Thus, the dermal LD50 in male and female rats was estimated to be greater than 5045 mg/kg bw.

Other routes

Male and female rats and mice (5 per sex) were exposed to Glycerides, mixed C8-C10 and succinyl at 5 mL/kg bw (5045 mg/kg bw) by a single intraperitoneal injection (Consultox Laboratories Ltd., 1979). None of the treated animals died and no systemic toxicity (clinical signs, body weight changes) were observed in either species up to the end of the 14-day observation period. Thus, with an LD50 > 5045 mg/kg bw, the substance was not acutely toxic to rats and mice by the intraperitoneal route.

Conclusions for acute toxicity

The acute oral toxicity of Glycerides, mixed C8-C10 and succinyl has been investigated in rats and mice, all studies resulting in LD50 values > 5000 mg/kg bw and without evidence of systemic toxicity. Likewise, testing for acute dermal toxicity resulted in a dermal LD50 value > 5045 mg/kg bw and no signs of systemic toxicity in rats. Furthermore, the substance is not acutely toxic by the intraperitoneal route (LD50 > 5045 mg/kg bw in rats and mice).

There are no data available on the acute toxicity by inhalation of Glycerides, mixed C8-C10 and succinyl. Human exposure by inhalation is unlikely given the low vapour pressure of the substance. However, exposure to aerosols, particles or droplets of inhalable size cannot be fully ruled out if the substance is used in formulated products intended for spraying or brushing applications. Therefore, assessment of acute toxicity via inhalation is conducted by means of read-across. Acute inhalation studies with the substance Glycerides, mixed decanoyl and octanoyl (CAS No. 73398-61-5) resulted in an LC50 > 1.86 mg/L (maximum attainable concentration of respirable particles) and no toxic effects.

Based on the available data the substance Glycerides, mixed C8-C10 and succinyl is considered to be not toxic by the oral, dermal and inhalation routes.

Justification for selection of acute toxicity – oral endpoint

The selected study is the most adequate and reliable study with the lowest dose descriptor.

Justification for selection of acute toxicity – inhalation endpoint

Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on substance specific studies and read-across from a structural analogue, the available data on the acute toxicity of Glycerides, mixed C8-C10 and succinyl 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.