Glycerol trioctanoate

Endpoint summary

Description of key information

Oral (OECD 401, read across): LD50 male/female rat > 5000 mg/kg bw

Inhalation (similar to OECD 403, read across): LC50 male rat > 1.86 mg/L air

Dermal (OECD 402, read across): LD50 male/female rat > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

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

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

weight of evidence

Justification for type of information:

refer to analogue justification provided in 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 source

Key result

Sex:

male/female

Dose descriptor:

LD50

Remarks:

rat

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

Source: CAS 26402-26-6

The in vivo acute oral toxicity data from the source substance octanoic acid, monoester with glycerol (CAS 26402-26-6) was obtained from a study conducted according to OECD guideline 401 under GLP conditions, and was selected as most reliable within the available source substance data. In vivo acute oral toxicity data of three additional substances with similar structure were available and used as source substances in a weight of evidence approach.

Results for additional source substances:

Source substance	Sex	Dose descriptor	Effect level	Based on
CAS 142-18-7	male/female	LD50 rat	> 20000 mg/kg bw	test mat.
CAS 73398-61-5	female	LD50 mouse	> 23625 mg/kg bw	test mat.
CAS 620-67-7	male/female	LD50 rat	> 4820 mg/kg bw	test mat.

 

 

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

The read across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their acute toxicity potential. The acute oral LD50 was found to be > 2000 mg/kg bw for the source substance Octanoic acid, monoester with glycerol (CAS 26402-26-6), triglycerides, mixed decanoyl and octanoyl (CAS 73398-61-5), propane-1,2,3-triyl triheptanoate (CAS 620-67-7), and 2,3-dihydroxypropyl laurate (CAS 142-18-7). Therefore, an acute oral LD50 value of >2000 mg/kg bw was considered for the hazard assessment and C&L purposes for the target substance glycerol trioctanoate (538-23-8).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

publication mostly in japanese language

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study was conducted in 1970, prior to the adoption of any OECD guidelines.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

mouse

Strain:

other: dd

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 18 - 20 g
- Diet (e.g. ad libitum): ad libtum
- Water (e.g. ad libitum): ad libtum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 25
- Humidity (%): 55 - 60

Route of administration:

oral: gavage

Vehicle:

other: Tween 80 and Span 80

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 1.2 w/v in Tween 80 and 0.8 w/v% Span 80
- Justification for choice of vehicle: Due to limited water solubility

Doses:

34200 mg/kg bw (males)
29600 mg/kg bw (females)

No. of animals per sex per dose:

Not stated

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Other examinations performed: clinical signs,

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

34 200 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

29 600 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was observed but no detailed information was available.

Clinical signs:

other: Increase in motor activity and respiratory rate was observed 5 min after administration. Thereafter, suppressed motor activity, decreased breathing and loss of righting reflex were observed. After several hours, these changes disappeared. After administra

Interpretation of results:

study cannot be used for classification

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

publication mostly in japanese language

Qualifier:

no guideline followed

Principles of method if other than guideline:

Study was conducted in 1970, prior to the adoption of any OECD guidelines.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 100 - 120 g
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 - 25
- Humidity (%): 55 - 60

Route of administration:

oral: gavage

Vehicle:

other: Tween 80 and Span 80

Doses:

34200 mg/kg bw (males)
33300 mg/kg bw (females)

No. of animals per sex per dose:

Not available

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 7 days
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs,

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

34 200 mg/kg bw

Based on:

test mat.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

33 300 mg/kg bw

Based on:

test mat.

Mortality:

No data available

Clinical signs:

other: Decreased in motor activity was observed after administration of 10 mL/kg but time point was not stated. Surpressed breathing and loss of righting reflex was observed after administration of 20 mL/kg. Soft stool and diahorrea was observed by 24 hours.

Interpretation of results:

study cannot be used for classification

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises adequate and reliable studies (Klimisch scores 1-2) and additional secondary literature (Klimisch score 4). The selected studies are sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 1.86 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

6 h

Remarks on result:

other:

Remarks:

Source: CAS 73398-61-5

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

The read across approach is justified in the analogue justification. The target and source substance are considered unlikely to differ in their acute toxicity potential. The acute inhalation LC50 was found to be > 1.86 mg/L air (maximum attainable concentration) for the source substance triglycerides, mixed decanoyl and octanoyl (CAS 73398-61-5). Therefore, the target substance glycerol trioctanoate (538-23-8) is not expected to be hazardous following acute inhalation exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Remarks:

rat

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other:

Remarks:

Source: CAS 620-67-7

The in vivo acute dermal toxicity data from the source substance propane-1,2,3-triyl trisheptanoate (CAS 620-67-6) was obtained from a study conducted according to OECD guideline 402 under GLP conditions, and was selected as most suitable within the available source substance data based on study reliability and chemical structure similarity to the target substance. In vivo acute dermal toxicity data of an additional substance with similar structure was available and used as source substance in a weight of evidence approach:

Result for the additional source substance:

Source substance	Sex	Dose descriptor	Effect level	Based on
CAS 91052-13-0	male/female	LD50 rat	> 2000 mg/kg bw	test mat.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

The read across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their acute toxicity potential. The acute dermal LD50 was found to be ≥2000 mg/kg bw for the source source substances propane-1,2,3-triyl triheptanoate (CAS 620-67-7). Therefore, an acute dermal LD50 value of 2000 mg/kg bw was considered for the hazard assessment and C&L purposes for the target substance glycerol trioctanoate (538-23-8).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Justification for read-across

Only limited data on the acute oral toxicity of glycerol trioctanoate (CAS 538-23-8) and no data on its acute dermal and acute inhalation toxicity are available. The assessment of acute toxicity was therefore based on studies conducted with analogue (source) substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity

CAS 538-23-8

The acute oral LD50 value of glycerol trioctanoate (CAS 538-23-8), named Tricaprylin, was reported to be 34.2 g/kg bw in male and 29.6 g/kg in female mice; for rats the acute oral LD50 values were reported to be 34.2 g/kg bw in male and 33.3 g/kg bw in female rats (WoE, 1970). These secondary source data had limited documentation details and could not be used for classification and labelling.

CAS 26402-26-6

In an acute oral toxicity study performed according to OECD guideline 401 under GLP conditions, 5 male and 5 female Sprague Dawley rats were administered octanoic acid, monoester with glycerol (CAS 26402-26-6) at a limit dose of 5000 mg/kg bw via gavage (WoE, 1989). No mortality and no clinical signs of toxicity occurred up to the end of the 14-day observation period. Under the conditions of this experiment, the oral LD50 value for male and female Sprague Dawley rats is > 5000 mg/kg bw.

CAS 73398-61-5

In an acute oral toxicity study performed similar to OECD guideline 401, 10 female mice were administered triglycerides, mixed decanoyl and octanoyl (CAS 73398-61-5) at doses of 12.5, 20 and 25 mL/kg bw via gavage (WoE, 1977). Based on a density of 945 mg/cm³ these doses were equivalent to 11812.5, 18900 and 23625 mg/kg bw. Deaths occurred within 24 to 48 hours in the 20 and 25 mL/kg dose groups. No information on the number of dead animals was given in the study report. All the survivors in the 20 and 25 mL/kg dose groups appeared asymptomatic by Day 3, although certain individuals showed a slight loss in weight at Day 7. No mortality was reported for the group dosed at 12.5 mL/kg bw. No further details on mortality were given, and the oral LD50 value was reported to be > 23.6 g/kg bw in female mice.

CAS 620-67-7

In an acute oral toxicity study performed similar to OECD guideline 401, 5 male and 5 female Wistar rats were administered propane-1,2,3-triyl triheptanoate (CAS 620-67-7) at a dose of 5 mL/kg bw via gavage (equivalent to 4820 mg/kg bw) (WoE, 1974). No mortality and no clinical signs of toxicity were observed up to the end of the 14-day observation period. Based on a density of 0.964 g/mL the oral LD50 value for male and female rats was found to be > 4820 mg/kg bw.

CAS 142-18-7

The acute oral toxicity of 2,3-dihydroxypropyl laurate (CAS 142-18-7) was investigated in Wistar rats according to the national FDA guideline "Appraisal of the safety of chemicals in foods, drugs and cosmetics" (WoE, 1977). In this experiment, 2 groups of 5 animals per sex and dose were administered the test material in the vehicle (corn oil) by gavage at doses of 10000 and 20000 mg/kg bw, respectively. One male and one female treated with 20000 mg/kg bw died 48 h after test substance application. No mortality was observed at 10000 mg/kg bw during the 7-day observation period. At both dose levels, slight staggering, ataxia and piloerection were observed 1 and 3 h post-application (number of animals not specified). However, these effects were reversible within 24 h. Body weight gains were reduced in the surviving males and females of the 20000 mg/kg bw group from Day 0 to Day 7. This effect was mainly attributed to a strong decrease in body weight in 1/4 males and 1/4 females at study termination (ca. -11 and -28%, respectively). The body weight gain of the remaining 3 animals per sex ranged from 4 to 7% (males) and 10 to 19% (females). The body weight gain of male and female animals treated with 10000 mg/kg bw was within the normal range. The mean group body weight gain was about 14 and 18% for males and females, respectively. Necropsy revealed no substance-related findings in the examined organs (brain, lung, heart, stomach, intestine, liver, spleen, kidneys, serous membrane/vessels, lymph nodes and gonads). Based on the results, the oral LD50 value for male and female Wistar rats is > 20000 mg/kg bw.

Acute inhalation toxicity

CAS 73398-61-5

The acute inhalation toxicity of triglycerides, mixed decanoyl and octanoyl (CAS 73398-61-5) was studied in male Sprague Dawley rats according to OECD guideline 403 under GLP conditions (key, 1976). A group 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. Ten 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 inhalation LC50 value for male rats is > 1.86 mg/L.

Acute dermal toxicity

CAS 620-67-7

The acute dermal toxicity of propane-1,2,3-triyl trisheptanoate (CAS 620-67-6) was tested in accordance with OECD guideline 402 under GLP conditions (key, 1993). Five male and 5 female Wistar rats were exposed to the test substance at a limit dose of 2000 mg/kg bw for 24 h. The test substance was applied unchanged to the shaved skin of the test animals under semi-occlusive conditions. After 24-h exposure, residual test substance was removed and animals were observed for 14 days. No treatment-related mortalities occurred and no signs of systemic toxicity were observed. All animals showed the expected gain in body weight. No test substance-related abnormalities were found at macroscopic post-mortem examination of the animals. Based on these results, the dermal LD50 value for male and female rats is > 2000 mg/kg bw.

CAS 91052-13-0

The acute dermal toxicity of Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates was investigated in a limit test according to OECD guideline 402 under GLP conditions (supporting study, 2010). Five male and 5 female Wistar rats were treated with the test substance at a dose of 2000 mg/kg bw. The test substance was dissolved in polyethylene glycol at a concentration of 200 mg/mL and applied onto the shaved skin of the test animals (10 mL/kg bw) for 24 h under occlusive conditions. After exposure, residual test substance was removed and animals were observed for a period of 14 days. No mortalities occurred and body weight gain of all animals was within the normal range during the whole study period. Flat posture was noted in all animals on Day 1. On the same day, chromodacryorrhoea was observed in 3/5 males and in 2/5 females. Ptosis was seen in 2/5 males and in 4/5 females, and 3/5 females showed restless behaviour on Day 1. Scales and scabs of the right flank and/or treated skin were observed among 3/5 males and 1/5 females between Days 4 and 15. At necropsy, no substance-related findings were noted. Therefore, the acute dermal LD50 value in male and female rats is > 2000 mg/kg bw.

Overall conclusion for acute toxicity

The reliable data available for the target and source substances indicate a very low level of acute toxicity following the oral, inhalation and dermal route, as LD50 and LC50 values were greater than the currently applied limit values. Therefore, as the available data did not identify any hazard for acute toxicity, glycerol trioctanoate (CAS 538-23-8) is not considered to be hazardous following acute exposure.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to glycerol trioctanoate (CAS 538-23-8), data will be generated from information on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the target substance information and analogue read-across approach, the available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.