Registration Dossier

Administrative data

Description of key information

All available acute oral toxicity studies within this category resulted in an acute oral LD50 > 2000 mg/kg bw.

All available acute dermal toxicity studies within the category resulted in acute dermal LD50 > 2000 mg/kg bw.

All available acute inhalation toxicity studies within the category resulted in acute inhalation LC50 > 1.86 mg/L air (maximum attainable concentration of respirable particles).

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Justification for grouping of substances and read-across

The Glycerides category covers aliphatic (fatty) acid esters of glycerol. The category contains both well-defined and UVCB substances with aliphatic acid carbon chain lengths of C2 (acetate) and C7-C22, which are mostly linear saturated and even numbered. Some of the substances in the category contain unsaturated fatty acids (e.g. oleic acid in 2,3-dihydroxypropyl oleate, CAS 111-03-5 or general fatty acids C16-22 (even) unsaturated in Glycerides, C14-18 and C16-22-unsatd., mono- and di-, CAS 91744-43-7). Some category members contain branched fatty acids. Branching is mostly methyl groups (e.g. isooctadecanoic acid, monoester with glycerol, CAS 66085-00-5 or 1,2,3-propanetriyl triisooctadecanoate, CAS 26942-95-0). In one category member the branching cannot be precisely located (Glycerides, C16-18 and C18-unsatd., branched and linear mono-, di- and tri, ELINCS 460-300-6). Hydroxylated fatty acids are present in three substances (Castor oil, CAS 8001-79-4; castor oil hydrogenated, CAS 8001-78-3 and 2,3-dihydroxypropyl 12-hydroxyoctadecanoate, CAS 6284-43-1). Hydroxylation occurs on C12 of stearic acid in all these substances. Acetylated chains are present in the last part of the category, comprising fatty acids from C8 to C18 (even) and also C18 unsaturated, additionally a C18 acetylated fatty acid is present with the acetic acid located in C12 position (e.g. Glycerides, castor oil mono-, hydrogenated acetates / 12-acetoxy-octadecanoic acid, 2,3-diacetoxy, CAS 736150-63-3). All glycerides build mono-, di- and tri-esters in variable proportions.

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate, environmental and human health hazards. Thus where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, 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 grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

 

Overview of Acute toxicity

CAS

Acute toxicity Oral

Acute toxicity inhalation

Acute toxicity dermal

142-18-7 (a)

Experimental result:
LD50 (male/female) >20000 mg/kg bw

RA: CAS 73398-61-5

WoE:
RA: CAS 620-67-7
RA: CAS 91052-13-0

25496-72-4 (b)

Experimental result:
LD50 (male/female) >39800 mg/kg bw

--

--

111-03-5

Experimental result:
LD50 (female) >2000 mg/kg bw

--

--

66085-00-5

Experimental result:
LD50 (male/female) >2000 mg/kg bw

--

--

6284-43-1

WoE:
RA: CAS 91845-19-1
RA: CAS 8001-78-3

RA: CAS 73398-61-5

RA: CAS 91845-19-1

620-67-7

Experimental result:
LD50 (male/female) >4820 mg/kg bw

RA: CAS 73398-61-5

Experimental result:
LD50 (male/female) >2000 mg/kg bw

122-32-7

Experimental result:
LD50 (male/female) >2000 mg/kg bw

RA: CAS 73398-61-5

WoE:
RA: CAS 555-43-1
RA: CAS 91845-19-1

555-43-1

Experimental result:
LD50 (male/female) >20000 mg/kg bw

RA: CAS 73398-61-5

Experimental result:
LD50 (male/female) >2000 mg/kg bw

26942-95-0

Experimental result:
LD50 (male/female) >2000 mg/kg bw

--

--

91052-47-0

WoE:
RA: CAS 31566-31-1
RA: CAS 85251-77-0
RA: MLCT

RA: CAS 73398-61-5

WoE:
RA: CAS 91845-19-1
RA: CAS 555-43-1

91744-09-1

WoE:
RA: CAS 31566-31-1
RA: CAS 85251-77-0
RA: CAS 91744-13-7
RA: CAS 91052-13-0
RA: MLCT

RA: CAS 73398-61-5

WoE:
RA: CAS 91845-19-1
RA: CAS 555-43-1
RA: CAS 91052-13-0

85536-07-8

WoE:
RA: CAS 73398-61-5
RA: CAS 91744-32-0
RA: CAS 65381-09-1

RA: CAS 73398-61-5

WoE:
RA: CAS 620-67-7
RA: CAS 91052-13-0

91052-49-2

RA: CAS 91744-28-4

RA: CAS 73398-61-5

WoE:
RA: CAS 91052-13-0
RA: CAS 555-43-1
RA: CAS 736150-63-3

67701-33-1

RA: CAS 85251-77-0

RA: CAS 73398-61-5

WoE:
RA: CAS 91052-13-0
RA: CAS 555-43-1
RA: CAS 91845-19-1

67784-87-6

RA: CAS 85251-77-0

RA: CAS 73398-61-5

WoE:
RA: CAS 555-43-1
RA: CAS 91845-19-1

91845-19-1

Experimental result:
LD50 (male/female) >5000 mg/kg bw

--

Experimental result:
LD50 (male/female) >2000 mg/kg bw

97358-80-0

WoE:
RA: CAS 26942-95-0
RA: CAS 66085-00-5

RA: CAS 73398-61-5

RA: CAS 555-43-1

91744-13-7

Experimental result:
LD50 (male/female) >2000 mg/kg bw

--

--

31566-31-1

Experimental result:
LD50 (female) >5000 mg/kg bw
RA: MLCT

RA: CAS 73398-61-5

WoE:
RA: CAS 91845-19-1
RA: CAS 555-43-1

85251-77-0

Experimental result:
LD50 (male/female) >2000 mg/kg bw
RA: MLCT

RA: CAS 73398-61-5

WoE:
RA: CAS 91845-19-1
RA: CAS 555-43-1

91744-32-0

Experimental result:
LD50 (male/female) >5000 mg/kg bw

--

--

91052-28-7

RA: CAS 91744-13-7

RA: CAS 73398-61-5

WoE:
RA: CAS 91052-13-0
RA: CAS 555-43-1
RA: CAS 91845-19-1

91052-54-9

Experimental result:
LD50 (male/female) >2000 mg/kg bw

RA: CAS 73398-61-5

WoE:
RA: CAS 91845-19-1
RA: CAS 555-43-1
RA: CAS 736150-63-3

91744-20-6

WoE:
RA: CAS 91744-13-7
RA: CAS 91052-13-0
RA: MLCT

RA: CAS 73398-61-5

WoE:
RA: CAS 91845-19-1
RA: CAS 555-43-1
RA: CAS 91052-13-0

97722-02-6

WoE:
RA: CAS 91744-13-7
RA: CAS 91052-13-0
RA: MLCT

RA: CAS 73398-61-5

WoE:
RA: CAS 91845-19-1
RA: CAS 555-43-1
RA: CAS 91052-13-0

77538-19-3

Experimental result:
LD50 (female) >2000 mg/kg bw

RA: CAS 73398-61-5

RA: CAS 736150-63-3

91744-28-4

Experimental result:
LD50 (male/female) >5000 mg/kg bw

RA: CAS 73398-61-5

WoE:
RA: CAS 91052-13-0
RA: CAS 555-43-1
RA: CAS 736150-63-3

68606-18-8

RA: CAS 85536-06-7

RA: CAS 73398-61-5

WoE:
RA: CAS 620-67-7
RA: CAS 91052-13-0

65381-09-1

Experimental result:
LD50 (male/female) >5000 mg/kg bw

--

--

73398-61-5

Experimental result:
LD50 (female) >23625 mg/kg bw
RA: MLCT

Experimental result:
LC50 (male) >1.86 mg/L air

WoE:
RA: CAS 555-43-1
RA: CAS 620-67-7
RA: CAS 91052-13-0
RA: CAS 91845-19-1

85536-06-7

Experimental result:
LD50 (male/female) >2000 mg/kg bw

RA: CAS 73398-61-5

WoE:
RA: CAS 620-67-7
RA: CAS 555-43-1
RA: CAS 91052-13-0
RA: CAS 91845-19-1

67701-26-2

Experimental result:
LD50 (male/female) >2000 mg/kg bw
RA: MLCT

RA: CAS 73398-61-5

WoE:
RA: CAS 91845-19-1
RA: CAS 555-43-1
RA: CAS 91052-13-0

8001-78-3

Experimental result:
LD50 (male) >20000 mg/kg bw
RA: MLCT

RA: CAS 73398-61-5

WoE:
RA: CAS 91845-19-1
RA: CAS 555-43-1
RA: CAS 91052-13-0

97593-30-1 (C10 )

RA: 97593-30-1 (C12)

RA: CAS 73398-61-5

WoE:
RA: CAS 620-67-7
RA: CAS 91052-13-0
RA: CAS 736150-63-3

97593-30-1 (C12)

Experimental result:
LD50 (female) >5000 mg/kg bw

RA: CAS 73398-61-5

WoE:
RA: CAS 620-67-7
RA: CAS 91052-13-0
RA: CAS 736150-63-3

93572-32-8

WoE:
RA: CAS 85251-77-0
RA: CAS 91052-13-0

RA: CAS 73398-61-5

WoE:
RA: CAS 91052-13-0
RA: CAS 736150-63-3

91052-13-0

Experimental result:
LD50 (female) >2000 mg/kg bw
RA: MLCT

RA: CAS 73398-61-5

Experimental result:
LD50 (male/female) >2000 mg/kg bw

736150-63-3

--

--

Experimental result:
LD50 (male/female) >2000 mg/kg bw

no CAS

Short-, medium- and long-chain triglycerides (SCT, MCT, LCT) (c, d)

Experimental result:
LD50 (male/female) >5000 mg/kg bw

--

--

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

(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.

(c) Surrogate substances are either chemicals forming part of a related category of structurally similar fatty acid esters or precursors/breakdown products of category members (i.e. alcohol and fatty acid moieties). Available data on these substances are used for assessment of (eco )toxicological properties by read-across on the same basis of structural similarity and/or mechanistic reasoning as described below for the present category.

(d) Assessment of toxicological properties is conducted also taking into account available data on mixtures of synthetic and/or naturally occurring glycerides (e.g. vegetable oils), which cannot be identified by a (single) CAS/EC number. The test materials short-, medium- and long-chain triglycerides (SCT, MCT, LCT) and their combinations (e.g. MLCT, SALATRIM – a SLCT) comprise triesters of glycerol with fatty acid chain lengths of C2 and C4 (short-chain), C8 and C10 (medium-chain) and C18 saturated/unsaturated (long-chain). The substance “mixture of mono-, di-, and triglycerides of lauric acid” comprises mono-, di and triesters of glycerol with dodecanoic acid (C12). The substance “Modified triglyceride” contains main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol, comprising triesters of glycerol with hexadecanoic (C16) and (9Z)-Octadec-9-enoic acid (C18:1). Available data on identity and composition of the individual test material for a given study is provided in the technical dossier.

For all category members registered under REACh a full data set for each endpoint is provided. For substances not subject to the current REACh Phase-in registration, lack of data for a given endpoint is indicated by "--".

Acute oral toxicity

CAS No. 142-18-7

The acute oral toxicity of 2,3-dihydroxypropyl laurate was investigated in Wistar rats according to the national FDA guideline "Appraisal of the safety of chemicals in foods, drugs and cosmetics" (Sterner, 1977). In this experiment, 2 groups of 5 animals per sex and dose were administered the test material in 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.

In a further acute oral toxicity study performed similar to OECD 401, 31 male rats were gavaged with the test substance at unspecified dose levels (Eagle and Poling, 1955). Calculation of the LD50 was made by the method of Reed and Muench (1938). Based on this calculation, the oral LD50 value for male rats was 53.4 mL/kg bw, corresponding to 52866 mg/kg bw based on a density of 0.99 g/mL.

CAS No. 66085-00-5

In an acute oral toxicity study performed according to OECD guideline 401 and in compliance with GLP, Glycerol monoisostearate was administered via gavage to groups of 5 Sprague Dawley rats per sex at a limit dose of 2000 mg/kg bw (Saboureau, 1989). No mortalities and no clinical signs were observed in the animals up to the end of the 14-day observation period. The increase in body weight was within the normal range reported for animals of this strain. Gross pathology did not reveal any substance-related findings in the treated animals. Therefore, the oral LD50 value for male and female Sprague Dawley rats is > 2000 mg/kg bw.

CAS No. 620-67-7

An acute oral toxicity study similar to OECD guideline 401 was performed with Propane-1,2,3-triyl trisheptanoate (Sasol Germany GmbH, 1974). In this experiment, Wistar rats were allocated to groups of 5 per sex and treated with the test substance via gavage at a dose volume of 5 mL/kg bw, corresponding to a limit dose of 4820 mg/kg bw as calculated from a density of 0.964 g/mL. Up to the end of the 14-day observation period, no mortalities and no clinical signs of toxicity were observed. Body weight changes and gross pathology were not examined in this study. Based on these data, an oral LD50 greater than 4820 mg/kg bw was derived for male and female Wistar rats.

A further oral toxicity study similar to OECD guideline 401 was conducted in male NMRI mice (Dufour, 1993). A group of 5 animals received the undiluted test substance via gavage at a limit dose of 5000 mg/kg bw. No mortalities were observed up to the end of the 6-day observation period. Within the first hours post-administration, clinical signs included half closed eyes, shortness of breath and little displacement. However, these effects were fully reversible within 2 h after test substance administration. No effects on body weights were noted. Necropsy revealed no substance-related macroscopic findings. Therefore, the oral LD50 was determined > 5000 mg/kg bw for male NMRI mice.

CAS No. 122-32-7

The acute oral toxicity of 9-Octadecenoic acid (Z)-, 1,2,3-propanetriyl ester was investigated in a GLP-conform study according to OECD guideline 401 (Reijnders, 1988). Groups of 5 Wistar rats per sex received the test substance via gavage at a limit dose of 2000 mg/kg bw. No mortality and no signs of toxicity occurred during the 14-day observation period. All animals showed the expected gain in body weight. Macroscopic examination of animals at termination did not reveal any treatment-related findings. Based on the results of the study, an oral LD50 value > 2000 mg/kg bw was determined for male and female Wistar rats.

CAS No. 555-43-1

In an acute oral toxicity study performed similar to OECD guideline 401, 5 male and 5 female Sprague Dawley rats were administered Glycerol tristearate diluted in arachis oil at a limit dose of 20000 mg/kg bw via gavage (Collier, 1980). No mortality occurred up to the end of the 14-day observation period. Evidence of overt toxicity was confined to subdued activity and piloerection within 1 h of dosing, but these effects were fully reversible 4 h after test substance administration. No significant effect on body weights was observed. Gross necropsy revealed no abnormal macroscopic lesions. Under the conditions of this experiment, the oral LD50 for male and female Sprague Dawley rats is > 20000 mg/kg bw.

CAS No. 26942-95-0

An acute oral toxicity study with 1,2,3-propanetriyl triisooctadecanoate was performed in Sprague Dawley CFY rats according to OECD guideline 401 and under conditions of GLP (Jones, 1987). The test substance was administered via gavage at a limited dose of 2000 mg/kg bw to a group each consisting of 5 males and females. No mortality occurred during the study period and no signs of toxicity were noted up to the end of the 14-day observation period. No effect on body weight was noted and gross pathology did not reveal any abnormal findings related to treatment. Under the conditions of this study, the oral LD50 value for male and female Sprague Dawley CFY rats is considered to be > 2000 mg/kg bw.

CAS No. 67701-33-1

Two studies on the oral acute toxicity of Glycerides, C14-18 mono- and di- performed are available, but only limited data is given on test conditions. Thus, these studies were not considered reliable sources. In both studies, 10 male Wistar rats were exposed to the test substance at a limit dose of 5000 mg/kg bw, which did not result in any mortalities and clinical signs up to the end of the 8-day observation period (Gloxhuber, 1975 and 1977).

CAS No. 91845-19-1

The acute oral toxicity of Glycerides, C16-18 and C18-hydroxy mono- and di- was studied in male and female Sprague Dawley rats according to EU method B.1 and under the requirements of GLP (Potokar, 1984). Groups of 5 animals per sex were treated with the test substance diluted in arachis oil at a limit dose of 5000 mg/kg bw via gavage. No mortality occurred during the study period. All test animals showed reduced activity 10 min to 5 h after test substance application. Additionally, 3/5 males and 1/5 females showed diarrhoea 8 h after treatment. No further clinical sings were observed during the 14-day observation period. No adverse effects on body weight development were noted during the study. At necropsy, 2/5 males and all females showed pneumonia, which was not attributed to substance treatment. Based on the results of this study, the oral LD50 value for male and female Sprague Dawley rats is > 5000 mg/kg bw.

CAS No. 91744-13-7

In an acute oral toxicity study performed according to OECD guideline 401 and in compliance with GLP, 5 male and 5 female Wistar rats were orally exposed to 2000 mg/kg bw C14-18 and C16-22-unsatd. mono- and di- diluted in an aqueous solution of carboxymethyl cellulose (1%) and Cremophor (0.5%) (Sterzel, 1990). No mortalities and no clinical signs of toxicity occurred during the 14-day observation period. Body weight development was not affected in treated animals. Necropsy and histopathological examination revealed no substance-related findings. In one female, a bilateral hydrometra was observed which was not considered treatment-related but rather a by chance finding. Therefore, the oral LD50 value for male and female Wistar rats is > 2000 mg/kg bw.

CAS No. 85251-77-0

The acute oral toxicity of Mono and diglycerides of fatty acids (Glycerides, C16-18 mono- and di-) was investigated in Ico: OFA SD rats according to OECD guideline 401 and under conditions of GLP (Ruat, 1999). The test substance was diluted in olive oil and administered to 5 male and 5 female animals at a limit dose of 2000 mg/kg bw via gavage. No mortalities and no abnormal clinical signs were reported up to the end of the 14-day observation period. Body weights were not affected by treatment and no macroscopic findings were observed in the animals at necropsy. Based on these results, the oral LD50 value for male and female Ico: OFA SD rats is > 2000 mg/kg bw.

CAS No. 91744-32-0

In a study performed similar to OECD 401, the acute oral toxicity of Glycerides, C8-10 mono-, di- and tri- was investigated in male and female Sprague Dawley rats (Collier and Wilson, 1984). Groups of 5 animals per sex received the undiluted test substance at a limited dose of 5000 mg/kg bw. No mortalities occurred during the 14-day observation period. Clinical signs were observed 30 min to 5 h after treatment and persisted up to 1 day after application of the test substance. Signs of reaction to treatment included pilo-erection, hunched posture, lethargy and a decreased respiratory rate in all animals, whereas ptosis was only seen in 3 male rats. Body weight development was not affected by treatment and necropsy revealed no substance-related findings. Based on these result, the oral LD50 value for male and female Sprague Dawley rats > 5000 mg/kg bw.

CAS No. 31566-31-1

The acute oral toxicity of Stearic acid, monoester with glycerol was investigated in a study performed similar to OECD guideline 401 (Dufour, 1993). A groups of 5 female NMRI EOPS mice received the test substance orally at a limit dose of 5000 mg/kg bw. No mortality occurred during the 6-day observation period. Clinical signs during the first hour post-administration involved eyes half closed, shortness of breath and apathy, but these signs were fully reversible two hours after administration. All animals showed the expected gain in body weight. Macroscopic examination of animals at termination did not reveal any treatment-related findings. Based on the results of the study, an oral LD50 value > 5000 mg/kg bw was determined for female NMRI mice.

A further oral toxicity study similar to OECD guideline 401 was conducted in male NMRI EOPS mice (Dufour, 1992). A group of 5 animals received the undiluted test substance orally at a limit dose of 5000 mg/kg bw. No mortalities and clinical signs were observed up to the end of the 6-day observation period. No effects on body weights were noted. No gross pathology examination was performed. Based on the study results, the oral LD50 was determined > 5000 mg/kg bw for male NMRI EOPS mice.

CAS No. 91052-54-9

An acute oral toxicity study with Glycerides, C16-18 mono-, di- and tri- was performed in Sprague Dawley rats according to OECD guideline 401 and under conditions of GLP (Jones, 1988). The animals (5 per sex) were exposed to the test substance in arachis oil at a limit dose of 2000 mg/kg bw. No mortalities and no signs of systemic toxicity were observed up to the end of the 14-day observation period. The animals showed normal gain in body weight and no adverse findings were noted at necropsy. Based on these results, the oral LD50 for male and female Sprague Dawley rats is > 2000 mg/kg bw.

CAS No. 77538-19-3

In an acute oral toxicity study performed similar to OECD guideline 401, Docosanoic acid ester with 1,2,3-propanetriol was administered via gavage to 5 female Swiss mice at a limit dose of 2000 mg/kg bw (Bouffechoux, 1996). No mortalities and no clinical signs were observed in the animals up to the end of the 14-day observation period. No effects on body weights were noted during the study. Based on these results, the oral LD50 value female Swiss mice is > 2000 mg/kg bw.

CAS No. 91744-28-4

The acute oral toxicity of Glycerides, C12-18 di- and tri- was investigated in a GLP-conform study performed according to OECD guideline 401 (Jones, 1989). Groups of 5 Sprague Dawley rats per sex received the undiluted test substance via gavage at a limit dose of 5000 mg/kg bw. No mortality and no signs of toxicity occurred during the 14-day observation period. All animals showed the expected gain in body weight. Macroscopic examination of animals at termination did not reveal any treatment-related findings. Based on the results of the study, the oral LD50 value for male and female Sprague Dawley rats is > 5000 mg/kg bw.

CAS No. 65381-09-1

A GLP-compliant acute oral toxicity study with Decanoic acid, ester with 1,2,3-propanetriol octanoate was performed in Sprague Dawley rats according to OECD guideline 401 (Jones, 1988). Groups of 5 animals per sex were treated with the undiluted test substance at a limit dose of 2000 mg/kg bw via gavage. No mortalities and no clinical signs were observed up to the end of the 14-day observation period. All animals showed the expected gains in body weight over the study period. Gross examination did not reveal any treatment-related effects in the animals. Based on these results, the oral LD50 value for male and female Sprague Dawley rats is greater than 2000 mg/kg bw.

CAS No. 73398-61-5

The acute oral toxicity of Triglycerides, mixed decanoyl and octanoyl was investigated in Tyler's Original Strain mice in an early study similar to OECD guideline 401 (Poole, 1977). Ten female animals per dose were gavaged with the undiluted test substance at volumes of 12.5, 20 and 25 mL/kg bw, which were equivalent to doses of 11812.5, 18900 and 23625 mg/kg bw as calculated from a density of 0.945 g/mL. Mortality was observed within 24-48 h in animals receiving the test substance at 20 and 25 mL/kg bw (number of dead animals not reported). Ataxia, lethargy, dyspnoea and diuresis were observed within 15 min of treatment. Complete loss of activity was observed in several animals within 2 h after administration, although other individuals were found to become more active at this time. All survivors appeared asymptomatic from Day 3 up to the end of the study period. Some individuals showed a slight loss in body weight at Day 7. Based on these results, the oral LD50 value for female Tyler's Original Strain mice was determined to be > 23625 mg/kg bw.

CAS No. 85536-06-7

In a GLP-compliant study performed according to OECD guideline 401, the acute oral toxicity of Glycerides, C8-18 was investigated in male and female Sprague Dawley rats (Higton, 1988). The animals (5 per sex and dose) received the test substance in arachis oil at a limit dose of 2000 mg/kg bw and were observed for a period of 14 days. During the whole study, no mortalities and no signs of systemic toxicity were observed. The animals showed the expected gain in body weight and no abnormalities were noted at necropsy at the end of the study. Under the conditions of this study, the oral LD50 for male and female Sprague Dawley rats is > 2000 mg/kg bw.

CAS No. 67701-26-2

An acute oral toxicity study with Glycerides, C12-18 was performed in Sprague Dawley rats according to OECD guideline 401 and under conditions of GLP (Jones, 1988). The animals (5 per sex) were exposed to the test substance in arachis oil at a limit dose of 2000 mg/kg bw. No mortalities and no signs of systemic toxicity were observed up to the end of the 14-day observation period. The animals showed normal gain in body weight and no adverse findings were noted at necropsy. Based on these results, the oral LD50 for male and female Sprague Dawley rats is > 2000 mg/kg bw.

Furthermore, an acute oral toxicity study similar to OECD guideline 401 was performed with Glycerides, C12-18 (Sasol Germany GmbH, 1976). In this experiment, Tyler's Original Strains mice were allocated to groups of 5 per sex and treated with the undiluted test substance or a dilution of the test substance in arachis oil at a limit dose of 5000 mg/kg bw via oral gavage. Up to the end of the 14-day observation period, no mortalities were observed. Based on these data, an oral LD50 greater than 5000 mg/kg bw was derived for male and female Tyler's Original Strains mice.

A further acute oral toxicity study with Glycerides, C12-18 was performed in albino rats similar to OECD guideline 401 (Sasol Germany GmbH, 1972). Based on a preliminary range finding study, ten animals received the undiluted test substance via gavage at a dose volume of 5 mL/kg bw, corresponding to a limit dose of 4500 mg/kg bw as calculated from a density of 0.9 g/mL. Up to the end of the 14-day observation period, no mortalities and no clinical signs of toxicity were observed. Body weight changes and gross pathology were not examined in this study. Based on these data, an oral LD50 greater than 4500 mg/kg bw for rats was derived.

The low potential for acute toxicity of Glycerides, C12-18 was further supported in a study with 10 male Wistar rats showing no mortalities after receiving a dose of 10000 mg/kg bw. After administration of the test substance, temporary symptoms of apathy were observed and some animals suffered from a reduction in their general state of health, a coarsening of the fur and diarrhoea. However, all clinical signs rapidly and fully declined within the 8-day observation period. Therefore, an oral LD50 greater than 10000 mg/kg bw was derived for male Wistar rats.

CAS No. 8001-78-3

The acute oral toxicity of Castor oil was examined in 10 male Wistar rats in a study performed similar to OECD guideline 401 and in compliance with GLP (Gloxhuber, 1969). The animals received the test substance in Cremophor EL at a limit dose of 20000 mg/kg bw via oral gavage. No mortalities were observed up to the end of the 14-day observation period. After treatment, all animals showed clinical signs involving increased respiration rate, ruffled fur and diarrhoea. No effects on the body weight were observed during the study and no treatment-related findings were noted at necropsy. Based on these results, the oral LD50 value for male Wistar rats is > 20000 mg/kg bw.

CAS No. 97593-30-1

The acute oral toxicity of C12: Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates was studied in female HsdCpb:Wu rats at a limit dose of 2000 mg/kg bw according to the acute toxic class method (OECD guideline 423) and under the requirements of GLP (Gillissen, 2008). In two sequential steps, 3 animals each received formulations of test substance in corn oil via gavage. During the study period, no animal died and no clinical signs were observed. The body weights and gain were not affected by treatment and necropsy revealed no substance-related findings at study termination. Therefore, the oral LD50 value for female HsdCpb:Wu rats is > 2000 mg/kg bw. In accordance with OECD guideline 423, the oral LD50 cut-off of the test substance is considered to be > 5000 mg/kg bw.

CAS No. 91052-13-0

In a GLP-compliant gavage study investigating the acute oral toxicity of Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates, female Sprague Dawley were exposed to a limit dose of 2000 mg/kg bw in a stepwise procedure (3 rats per step) according to OECD guideline 423 (Otterdijk, 2010). No mortality was observed up to the end of the14-day observation period. Clinical signs involved hunched posture and/or piloerection in all females on Day 1 of the observation period. All animals showed the expected gain in body weights during the study and necropsy revealed no substance-related findings. Based on the results, the oral LD50 value for female Sprague Dawley rats is > 2000 mg/kg bw. In accordance with OECD guideline 423, the oral LD50 cut-off of the test substance is considered to > 5000 mg/kg bw.

Short-, medium- and long-chain triglycerides (SCT, MCT, LCT)

The acute oral toxicity of medium- and long-chain triacylglycerols (MLCT) was examined in Wistar rats in a study performed similar to OECD guideline 401 (Matulka, 2006). Five animals per sex received the undiluted test substance at a limit dose of 5000 mg/kg bw via oral gavage. No mortalities and no clinical signs of toxicity were observed up to the end of the 14-day observation period. No effects on the body weight were observed during the study and no treatment-related findings were noted at necropsy. Based on these results, the oral LD50 value for male Wistar rats is > 5000 mg/kg bw.

Acute inhalation toxicity

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.

Acute dermal toxicity

CAS No. 620-67-7

The acute dermal toxicity of propane-1,2,3-triyl trisheptanoate was tested in accordance with OECD guideline 402 and in compliance with GLP (Mürmann, 1993). In this study, 5 male and 5 female 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 semiocclusive 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 No. 555-43-1

In an acute dermal toxicity study, Glycerol tristearate was investigated in rats in accordance with OECD guideline 402 and in compliance with GLP (Krueger, 1998). The animals (5 per sex) were dermally exposed to the test substance at a limit dose of 2000 mg/kg bw. The powdery test substance was suspended in corn oil at a concentration of 40 g/100 m³ and applied onto the shaved skin of the test animals (5 cm³/kg bw) for 24 h under semiocclusive conditions. After exposure, residual test substance was removed and animals were observed for a period of 14 days. No treatment-related mortalities occurred and no signs of systemic toxicity were observed during the study. Male rats showed the expected gain in body weight throughout the study. Minimal body weight gain was recorded in 2/5 females, whereas 1/5 females showed no gain in body weight. However, this finding was not considered to be treatment-related, since it was considered a physiological finding in rats of this age. At necropsy, macroscopic examination revealed no test substance-related abnormalities. Based on these results, the dermal LD50 value for male and female rats is > 2000 mg/kg bw.

CAS No. 91845-19-1

The acute dermal toxicity of Glycerides, C16-18 and C18-hydroxy mono- and di- was tested in accordance with EU method B.3 and in compliance with GLP (Potokar, 1985). The study was performed as a limit test in rats (5 males and 5 females) at a dose level of 2000 mg/kg bw. The test substance was applied unchanged to the clipped skin of the test animals for 24 h under occlusive conditions. After removal of the test substance, animals were observed for a period of 14 days. No mortalities and no local dermal signs were noted during the course of the study. No clinical signs of toxicity were observed. Body weight gain was within the normal range in males and females during the whole study period. Necropsy and histopathological examination revealed no substance-related findings. One male and two female animals showed a reddening of the ileum mucosa, which was not considered to be related to treatment. Based on these results, the dermal LD50 value for male and female rats is > 2000 mg/kg bw.

CAS No. 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 and in compliance with GLP (Otterdijk, 2010). In this study, 5 male and 5 female 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 LD50 in male and female rats is > 2000 mg/kg bw.

CAS No. 736150-63-3

The acute dermal toxicity of Glycerides, castor-oil.mono, hydrogenated, acetates was tested in accordance with OECD guideline 402 and in compliance with GLP (Ott, 2003). In this study, 5 male and 5 female rats were exposed to a limit dose of 2000 mg/kg bw for 24 h under semiocclusive conditions. The test substance was dissolved in corn oil and applied to the clipped skin at a dose volume of 4 mL/kg bw. No mortality and no clinical signs of toxicity were observed up to the end of the 14-day observation period. Body weight gain was not affected by treatment with the test substance in male and female animals. No macroscopic findings were observed at necropsy. Thus, a dermal LD50 greater than 2000 mg/kg bw was derived for male and female rats.

Overall conclusion for acute toxicity

The acute oral toxicity of Glycerides has been extensively studied and data are available for numerous category members. Toxicologically relevant effects including mortality have been reported only in at very high dose levels exceeding the currently applicable limit dose value of 2000 mg/kg bw.

Inhalation is not a relevant route of exposure for Glycerides given the very low vapour pressure of all category members. Exposure to aerosols, particles or droplets of inhalable size cannot be excluded for formulated products intended for use in spraying applications. Acute inhalation studies with the substance Triglycerides, 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.

Several members of the Glycerides category have been tested for acute dermal toxicity. No mortality occurred in any of the available studies resulting in dermal LD50 values > 2000 mg/kg bw. No toxicologically relevant signs of systemic toxicity were reported.

Based on the available data and following the category approach, all members of the Glycerides category are considered to be not toxic after acute exposure by the oral, inhalation and dermal routes.

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 group concept is applied to the members of the Glycerides category, data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the group concept, the available data on acute 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.