Registration Dossier

Administrative data

Description of key information

All available subacute, subchronic and chronic repeated dose toxicity studies resulted in NOAELs ≥ 1000 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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 study available

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 Repeated dose toxicity

CAS

Repeated dose toxicity oral

Annex VIII

Repeated dose toxicity oral

Annex IX

142-18-7 (a)

WoE:
RA: CAS 91052-13-0
RA: CAS 97593-30-1 (C12)
RA: MLCT

WoE:
RA: mixture of mono-, di-, and triglycerides of lauric acid
RA: CAS 538-23-8
RA: CAS 736150-63-3
RA: MCT

111-03-5 (b)

Experimental result:
NOAEL (male/female) ≥1000 mg/kg bw/day

--

6284-43-1

RA: CAS 91845-19-1

WoE:
RA: CAS 8001-79-4
RA: CAS 736150-63-3

620-67-7

RA: CAS 538-23-8

RA: CAS 538-23-8

538-23-8

Experimental result:
NOAEL (male/female) = 1908 mg/kg bw/day

Experimental result:
NOAEL (male) = 4770 mg/kg bw/day

122-32-7

WoE:
RA: CAS 111-03-5
RA: MLCT

WoE:
RA: CAS 8001-79-4
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

555-43-1

WoE:
RA: CAS 91845-19-1
RA: MLCT

WoE:
RA: CAS 736150-63-3
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

91052-47-0

WoE:
RA: CAS 91845-19-1
RA: CAS 91052-13-0
RA: MLCT

WoE:
RA: CAS 736150-63-3
RA: CAS 8001-79-4
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

91744-09-1

WoE:
RA: CAS 91845-19-1
RA: CAS 91052-13-0
RA: MLCT

WoE:
RA: CAS 736150-63-3
RA: CAS 8001-79-4
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

85536-07-8

WoE:
RA: CAS 97593-30-1 (C12)
RA: CAS 538-23-8
RA: MLCT

WoE:
RA: CAS 538-23-8
RA: MCT

91052-49-2

WoE:
RA: CAS 91052-13-0
RA: CAS 97593-30-1 (C12)
RA: MLCT

WoE:
RA: CAS 736150-63-3
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

67701-33-1

WoE:
RA: CAS 91052-13-0
RA: CAS 91845-19-1
RA: MLCT

WoE:
RA: CAS 8001-79-4
RA: CAS 736150-63-3
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

67784-87-6

WoE:
RA: CAS 91052-13-0
RA: CAS 91845-19-1
RA: MLCT

WoE:
RA: CAS 8001-79-4
RA: CAS 736150-63-3
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

91845-19-1

Experimental result:
NOAEL (male/female) ≥1000 mg/kg bw/day

--

97358-80-0

--

RA: CAS 736150-63-3

31566-31-1

WoE:
RA: CAS 91845-19-1
RA: CAS 91052-13-0
RA: MLCT

WoE:
RA: CAS 736150-63-3
RA: CAS 8001-79-4
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

85251-77-0

WoE:
RA: CAS 91845-19-1
RA: CAS 91052-13-0
RA: MLCT

WoE:
RA: CAS 736150-63-3
RA: CAS 8001-79-4
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

91052-28-7

WoE:
RA: CAS 91052-13-0
RA: CAS 91845-19-1
RA: CAS 111-03-5
RA: MLCT

WoE:
RA: CAS 8001-79-4
RA: CAS 736150-63-3
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

91052-54-9

WoE:
RA: CAS 91052-13-0
RA: CAS 91845-19-1
RA: MLCT

WoE:
RA: CAS 736150-63-3
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

91744-20-6

WoE:
RA: CAS 91845-19-1
RA: CAS 91052-13-0
RA: MLCT

WoE:
RA: CAS 736150-63-3
RA: CAS 8001-79-4
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

97722-02-6

WoE:
RA: CAS 91845-19-1
RA: CAS 91052-13-0
RA: MLCT

WoE:
RA: CAS 736150-63-3
RA: CAS 8001-79-4
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

77538-19-3

WoE:
RA: CAS 112-85-6

WoE:
RA: CAS 736150-63-3
RA: CAS 56-81-5

91744-28-4

WoE:
RA: CAS 91052-13-0
RA: CAS 97593-30-1 (C12)
RA: MLCT

WoE:
RA: CAS 736150-63-3
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

68606-18-8

WoE:
RA: CAS 538-23-8
RA: CAS 91052-13-0
RA: CAS 97593-30-1 (C12)
RA: MLCT

WoE:
RA: CAS 538-23-8
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

73398-61-5

WoE:
Experimental result:
NOAEL (male) ≥10000 mg/kg bw/day
RA: CAS 538-23-8
RA: CAS 91052-13-0
RA: CAS 97593-30-1 (C12)
RA: MLCT

WoE:
Experimental result:
NOAEL (male/female) ≥5000 mg/kg bw/day
RA: CAS 736150-63-3
RA: CAS 8001-79-4
RA: CAS 538-23-8
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

85536-06-7

WoE:
RA: CAS 91052-13-0
RA: CAS 97593-30-1 (C12)
RA: CAS 538-23-8
RA: MLCT

WoE:
RA: CAS 538-23-8
RA: CAS 736150-63-3
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

67701-26-2

WoE:
RA: CAS 97593-30-1 (C12)
RA: MLCT
RA: CAS 91052-13-0

WoE:
RA: CAS 736150-63-3
RA: CAS 8001-79-4
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

8001-79-4

--

Experimental result:
NOAEL (rat; male/female) ≥5835/5725 mg/kg bw/day

8001-78-3

WoE:
RA: CAS 91845-19-1
RA: CAS 91052-13-0
RA: MLCT

WoE:
RA: CAS 736150-63-3
RA: CAS 8001-79-4
RA: MCT
RA: Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

97593-30-1 (C10 )

RA: CAS 97593-30-1 (C12)

WoE:
RA: CAS 538-23-8
RA: CAS 736150-63-3
RA: MCT

97593-30-1 (C12)

Experimental result:
NOAEL (male/female) ≥1000 mg/kg bw/day

WoE:
RA: CAS 538-23-8
RA: CAS 736150-63-3
RA: MCT

93572-32-8

WoE:
RA: CAS 91052-13-0
RA: CAS 97593-30-1 (C12)

RA: CAS 736150-63-3

91052-13-0

Experimental result:
NOAEL (male/female) ≥1000 mg/kg bw/day

RA: CAS 8001-79-4

736150-63-3

--

Experimental result:
NOAEL (male/female) ≥1333 mg/kg bw/day

no CAS

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

Experimental result:
NOAEL (rat; male) ≥16340 mg/kg bw/day

Experimental result:
NOAEL (dog; male/female) ≥3750 mg/kg bw/day;

no CAS

Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol (c, d)

--

Experimental result: NOAEL (male/female) ≥7500 mg/kg bw/day

56-81-5 (c)

--

Experimental result:
NOAEL (male/female) ≥10000 mg/kg bw/day

112-85-6 (c)

Experimental result:
NOAEL (male/female) ≥1000 mg/kg bw/day

--

(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 "--".

 

Repeated dose toxicity, oral, subacute

CAS No. 111-03-5

A GLP-compliant subacute oral toxicity study according to OECD 422 was performed with 2,3-dihydroxypropyl oleate at doses of 100, 300 and 1000 mg/kg bw/day (Yamaguchi, 2005). Male and female Sprague Dawley rats (12 per sex and group, except for 1000 mg/kg bw/day: only 7 males) received the test substance in corn oil once daily via gavage. A control group, consisting of 7 males and 12 females, was treated with the vehicle alone. The duration of treatment was 42 days (14 days prior to mating and 28 days thereafter) in males and 42-52 days (from 14 days before mating to day 4 of lactation) in females, respectively. Satellite groups of 5 animals per sex, each for the control and test groups, were used to investigate reversibility of effects during a 14-day post-exposure recovery period. No mortality and no clinical signs and effects on neurobehaviour were observed during the whole study period. No adverse effects on body weight development were observed during treatment and recovery period. The analysis of clinical, haematological and urinary parameters did not reveal any dose-dependent and toxicologically relevant changes in treated animals compared to controls. At 100 mg/kg bw/day, a significant decrease in absolute weight of seminal vesicles in males and a significant decrease in relative weight of spleen in females were observed at necropsy. Since these effects did not follow a dose-dependent relationship and were not accompanied by any histopathological changes in the respective organs, they were not considered to be toxicologically relevant. A decrease in relative weights of pituitary in males and thyroid in females was observed at 1000 mg/kg bw/day at the end of the recovery period. Since no abnormities were reported for these organs after the administration period, they were considered as not compound-related. No test substance-related changes were found at gross pathology. A low incidence of commonly found microscopic changes was observed, which was evenly distributed between all groups and therefore considered as incidental findings. Although one female showed a subcutaneous tumour of the mammary gland after 40 days exposure to 300 mg/kg bw/day, this benign fibroadenoma was considered to be generated naturally, since no effects were observed at the higher dose levels. Based on the overall effects observed in this subacute study, a NOAEL of 1000 mg/kg bw/day for male and female Sprague Dawley rats was derived.

CAS No. 538-23-8

A subacute oral toxicity study in Wistar rats was performed with Glycerol trioctanoate at dose volumes of 2, 5 and 10 mL/kg bw/day, corresponding to dose levels of 1908, 4770 and 9540 mg/kg bw/day, as calculated from a density of 0.954 g/mL (Ohta et al., 1970). The test substance was diluted in a mixture of 1.2% Tween 80/0.8% Span 80 in water and administered once daily to groups of 10 male and 10 female animals for a period of 31 days via gavage. A similar constituted control group received water as vehicle. After treatment with the test substance at 10 mL/kg bw/day, 2 males and females each died. Further, 2 males and 1 female of 5 mL/kg bw/day dose group died. No changes in body weight development and no changes in food consumption were noted between control and treated groups. At clinical chemistry and haematology, no treatment-related effects on the analysed parameters were observed, except for the concentration of urea nitrogen which was significantly lower in female rats dosed with 5 and 10 mL/kg bw. Urinary parameters were not altered in treated animals compared to controls. In males, a significant reduction in heart weight was observed over all dose groups compared to controls. At 5 and 10 mL/kg bw/day, a significant reduction in spleen and kidney weight was observed in males. The weight of the left testis was significantly decreased in all dose groups compared to controls. In addition, significant reduction in right testis weight was observed at 2 and 10 mL/kg bw/day. No changes in absolute and relative organ weights were found in treated females compared to controls. At necropsy, no treatment-related findings were reported. Histopathology revealed sporadic effects on liver, kidney, heart, lungs, spleen as well as extramedullary haematopoiesis, but these effects were also observed in animals of the control group and were thus not regarded to be treatment-related. Based on the results of the 31-day toxicity study, a NOAEL of 1908 mg/kg bw/day was derived for male and female Hsd Cpb:WU rats.

CAS No. 91845-19-1

To assess the subacute toxicity of Glycerides, C16-18 and C18-hydroxy mono- and di-, a GLP-conform study according to EU method B.7 was performed in Sprague Dawley rats at doses of 100, 500 and 1000 mg/kg bw/day (Potokar, 1985). The test substance in peanut oil or the vehicle alone was administered once daily to groups of 10 animals per sex via gavage for a period of 28 days. A satellite group of 5 males and 5 males, each for the control and 500 mg/kg bw/day dose groups, was included in the study to investigate reversibility of effects during a 33-day post-exposure recovery period. No mortality and no clinical signs were observed during the whole study period. At ophthalmological examination no adverse effects were reported. Body weight gain and food consumption were not altered between treated and control groups. Haematology and clinical chemistry analysis did not reveal any treatment-related changes in the animals. At macroscopic examination of the animals, no abnormal findings were observed. Histopathological examination of animals treated with 500 and 1000 mg/kg bw/day revealed non-inflammatory dilatation of lymph vessels in the small intestine as well as foreign body giant cells and vacuolization in Peyer Plaques. However, these findings were considered as adaptive responses to treatment, but not as adverse effects. Based on the study results, a NOAEL of≥ 1000 mg/kg bw/day was set for male and female Sprague Dawley rats.

CAS No. 97593-30-1

A subacute oral toxicity study according to OECD 407 and in compliance with GLP was performed with C12: Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates at doses of 100, 300 and 1000 mg/kg bw/day (Reißmüller, 2008). The test substance dissolved in corn oil or the vehicle alone was applied once daily to groups of 5 male and 5 female Hsd Cpb:WU rats via gavage for a period of 28 days. No mortalities and no clinical signs were observed, except for one female which showed increased motility and loss of hair which was considered as incidental finding. The analysis of functional observation battery parameters as well as motor and locomotor activity confirmed the effects of increased motility, but the quantification of results did not reveal a treatment-related effect when compared to controls. Body weight development was not affected in male rats, whereas mean bodyweights in females were marginally to slightly lower at 300 and 1000 mg/kg bw/day compared to controls. However, food consumption was unaffected and body weight gain of treated male and female animals was comparable to controls. Thus, effects on body weights in treated females were considered to be of no toxicological relevance. Water consumption was also not affected by treatment and comparable to controls. Treatment with the test-substance did not result in toxicologically relevant changes in clinical chemistry and haematology parameters. No effects on absolute and relative organ weights were observed in treated animals. At necropsy, observed findings were not attributable to treatment and considered to be incidental, since no dose-dependent effects were observed. Consistent with this, histopathological examination did not reveal any treatment-related findings but spontaneous in nature and considered common for rats of this strain and age. Based on the results of the 28-day toxicity study, a NOAEL of ≥ 1000 mg/kg bw/day was derived for male and female Hsd Cpb:WU rats.

CAS No. 91052-13-0

The subacute oral toxicity of Glycerides, C8-18 and C18-unsatd. mono- and di-, acetates was investigated in Crl:WI (Han) rats according to OECD guideline 422 and in conformity with GLP (Otterdijk, 2010). Dilutions of the test substance in polyethylene glycol were administered once daily to groups of 10 male and 5 female rats at doses of 100, 300 and 1000 mg/kg bw/day for 28 days via gavage. A similar constituted group received the vehicle and served as control. In addition, satellite groups of 5 males and 5 females each for the control and high dose group were used to investigate reversibility of effects during a 14-day post-exposure recovery period. No substance-related mortalities and clinical signs occurred during the whole study period. All parameters assessed at neurobehavioural examination were found to be normal and comparable to controls. Food consumption was similar between treated and control animals and no toxicologically relevant changes in body weights and body weight gain were noted up to 1000 mg/kg bw/day. Any statistically significant changes in clinical biochemistry and haematology parameters were considered to be of no toxicological relevance as these occurred in the absence of a clear treatment-related trend and remained within the range considered normal for rats of this age and strain. Any statistically significant changes in organ weights and organ to body weight ratios were considered to be of no toxicological relevance as these occurred in the absence of a clear treatment-related trend. Further, organ weight changes were within the range considered normal for rats of this age and strain and/or were present at the end of the recovery period only. In addition, no histopathological correlates were noted which could support organ weight changes. At necropsy, all incidental findings remained within the background range of findings that are encountered among rats of this age and strain. Since no dose-related trend was observed, these findings were considered to be of no toxicological relevance. Based on the results of this subacute toxicity study, the NOAEL for Crl:WI rats was considered to be ≥ 1000 mg/kg bw/day.

CAS 73398-61-5

A 30-day oral gavage study was performed with Glycerides, mixed decanoyl and octanoyl in male Wistar rats (Klimmer, 1971). Groups of 10 animals received daily doses of up to approx. 10 g/kg bw/day. No treatment related abnormalities were observed based on clinical signs, body weight gain, food consumption, urine analysis and gross pathology at any dose level. No other parameters were analysed. Based on the study results, a subacute NOAEL of ≥10000 mg/kg bw/day was found for male Wistar rats.

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

A subacute oral feeding study with medium- and long-chain triglyceride was performed in Wistar rats (Matsuo and Takeuchi, 2004). The effects of structured medium- and long-chain triacylglycerols (MLCT) in diets containing 50, 100, 150 or 200 g test substance/kg on body fat accumulation were compared with those of long-chain triacylglycerols (LCT). The concentrations of the test substance in the diet corresponded to mean doses of 4.09, 8.17, 12.26 and 16.34 g/kg bw/day, as calculated from the reported mean body weight and mean food intake values. The diets were fed daily to groups of 6 young adult male Wistar rats for a period of 56 days. No mortality and no clinical signs occurred during the study period. No adverse effects on body weights and body weight gain were observed in animals treated with the MLCT-containing diet compared to animals receiving the LCT-containing diet, which also corresponded to respective data on food consumption. No effects on liver weights were observed after treatment with the test substance compared to the LCT-fed groups. Perirenal adipose tissue weight and intra-abdominal adipose tissue weight was significantly lower in the 150 and 200 g/kg MLCT dose groups, when compared to the 150 and 200 g/kg LCT dose groups, but this changes were not considered to be adverse effects. The analysis of clinical chemistry parameters revealed a significant increase in serum triacylglycerol concentration in MLCT-fed rats compared to LCT-fed rats. Furthermore, hepatic capacities of the citrate synthase and cytochrome oxidase were significantly higher in rats fed the test substance, when compared to LCT-fed rats. However, these effects were not considered to be toxicologically relevant. Based on the overall effects observed in this study, the NOAEL for male Wistar rats was found to be ≥ 16.34 g/kg bw/day.

In a further subacute oral feeding study, male Wistar rats were administered medium- and long-chain triglycerides (MLCT) at a dietary concentration of 70g/kg diet, corresponding to approx. 3500 mg/kg bw/day (Matulka, 2006). Twenty animals received the test substance for a period of 6 weeks, whereas a further group of 20 animals was administered an isocaloric diet containing 7% long-chain triglycerides (rapeseed oil) and served as controls. No data on mortality and clinical signs were reported. There was no difference in body weight changes between the control and MLCT-treated group, although food consumption and caloric intake were significantly increased in the treatment group compared to control. Clinical chemistry analysis of MLCT-treated animals revealed a statistically significant decrease in total serum cholesterol. Other findings reported involved a statistically significant decrease in total body fat and body fat ratios (g body fat/energy intake) and a statistically significant increase in total carcass protein in MLCT-treated animals compared to controls. Based on these results, a NOAEL ≥ 3500 mg/kg bw/day was derived for male Wistar rats. However, due to lacking data on organ weights, gross pathology and histopathology, the results of this study were not taken into account for hazard assessment.

CAS No. 112-85-6

In a GLP-compliant subacute oral toxicity study performed according to OECD 422, male and female Sprague Dawley rats were exposed to docosanoic acid at doses of 100, 300 and 1000 mg/kg bw/day (Nagao et al., 2002). The test substance dissolved in corn oil was orally administered to 13 animals per sex and dose. Males were treated for a period of 42 days, whereas females were exposed to the test substance 14 days prior to mating and until Day 3 of lactation. A similar constituted group received the vehicle and served as control. No mortality and no clinical signs were observed during the study period. Body weights were not adversely affected by treatment. The body weight gain in males was slightly increased at 100 mg/kg bw/day compared to the other dose groups and the controls, which corresponded to higher food intake in these animals. A significant decrease in food consumption was observed in females of the same dose group during lactation. Since both effects were not dose-related, they were regarded to be of no toxicological relevance. A significant increase in absolute and relative liver weight in males and a significant decrease in absolute and relative kidney weights in females was observed at 100 mg/kg bw/day. Due to the absence of a dose-relationship, these effects were considered to be non-adverse. At necropsy, all dose groups showed sporadic effects on adrenal gland, thyroids, thymus, lung, liver, kidney and spleen in a few males and females without any dose-relationship, and were thus regarded as not treatment-related. Consistent with the findings at gross pathology, microscopic examination revealed sporadic changes in brain, heart, liver, spleen, kidney, adrenals, thymus and testes. The effects on heart, liver, spleen and kidney found in males of the highest dose (1000 mg/kg bw/day) group were comparable to males of the control group. In females, one case of thalamus mineralisation in the brain was found at the high dose level. Thus, effects observed at histopathology were not considered to be treatment-related. Based on these results, a NOAEL ≥ 1000 mg/kg bw/day was derived for male and female Sprague Dawley rats.

Repeated dose toxicity, oral, subchronic

CAS 73398-61-5

A 90-day oral feeding study was performed in young Wistar rats with mixed decanoyl and octanoyl glycerides (Klimmer, 1971). The test substance was mixed to the diet at concentrations of 10,000 and 50,000 ppm. 20 animals per dose were fed ad libitum. No treatment-related abnormalities were observed concerning clinical signs, body weight increase, food consumption, haematology, clinical chemistry, urine analysis and gross pathology. Thus, the NOAEL was found to be 5000 mg/kg bw/day assuming 1 ppm in food being equivalent to 0.1 mg/kg bw/day for young rats.

CAS No. 8001-79-4

The subchronic oral toxicity of Castor oil was investigated in male and female Fischer 344 rats in a GLP-conform study similar to OECD guideline 408 (NTP, 1992). The test substance was administered daily ad libitum for a period of 13 weeks to groups of 20 animals per sex at dietary concentrations of 0.62, 1.25, 2.50, 5 and 10% (w/w), corresponding to reported doses of 404, 809, 1583, 3067 and 5835 mg/kg bw/day in males and 401, 797, 1569, 3045, 5725 mg/kg bw/day in females, respectively. A similar constituted control group received the plain diet. Ten of the 20 animals per sex and group were used to analyse haematological and clinical chemistry parameters on Days 5 and 21 and at the end of the study. During the study period, no mortalities and no clinical signs were observed. Body weights and food consumption in treated animals were comparable to controls. No biologically relevant changes were observed in parameters of clinical chemistry and haematology on Days 5 and 21, and at the end of the study. The absolute and relative liver weights were increased at a dose level of 5835 mg/kg bw/day. An increase in relative heart weight in males was noted at 404, 1583 and 5835 mg/kg bw/day. Furthermore, a slight decrease in epididymal weight was observed in male animals of the middle and high dose groups. However, these effects were not considered to be treatment-related, since they occurred in the absence of dose-dependency and any correlating histopathological changes. Macroscopic and microscopic examinations did not reveal any substance-related effects in animals of all dose groups. Based on the overall effects of the study, a NOAEL of ≥ 5835 and 5725 mg/kg bw/day for male and female Fischer 344 rats, respectively, was derived.

In a further subchronic oral toxicity study performed similar to OECD guideline 408, the test substance was administered to B6C3F1 mice at dietary concentrations of 0.62, 1.25, 2.50, 5 and 10% (w/w), corresponding to reported doses of 917, 2022, 3800, 7823, 15017 mg/kg bw/day in males and 1153, 2282, 5009, 9627, 16786 mg/kg bw/day in females, respectively (NTP, 1992).20 animals per sex and group received the test substance in the diet or plain diet (controls) daily ad libitum for 13 weeks. Ten of the 20 animals per sex and group were used to analyse haematological and clinical chemistry parameters on Days 5 and 21. At study termination, no mortalities, no clinical signs and no biologically relevant changes in body weights and food consumption were observed in all treated animals compared to controls. No effects on parameters of clinical chemistry and haematology were observed in treated all animals compared to controls. At 9627 and 16786 mg/kg bw/day, liver weights were increased in both sexes, whereas at the same dose levels kidney weights were only increased in females. Since the effects were marginal and not supported by histopathological findings, they were considered as non-adverse. Gross pathology and histopathology did not reveal any substance-related findings in animals of all dose groups. Based on the results of this study, the NOAEL for male and female B6C3F1 mice was set at ≥ 15017 and 16786 mg/kg bw/day, respectively.

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

A subchronic oral toxicity study with medium chain triglycerides (MCT) was performed similar to OECD guideline 409 in beagle dogs at concentrations of 5, 10 and 15 % in the diet, corresponding to 1250, 2500 and 3750 mg/kg bw/day, as calculated from an assumed food consumption of 25 g/kg bw/day (Matulka et al., 2009). Four animals per sex and dose received the test substance once daily during a 3-h feeding regimen for a period of 91 days, whereas a control group was administered the plain diet. No signs of toxic effects and no mortality were observed in any of the animals during the study period. The mean body weight was not altered between control and treated animals. As compared to the control group, all three MCT groups had several consecutive days of reduced food consumption at the beginning and near the end of study. These periods of reduced food intake were not significant to the overall food consumption rates, but were thought to be related to palatability of MCT in feed. No treatment-related effects were found at ophthalmological examination of the animals. In addition, alterations in urinary, serum clinical and haematological parameters were observed in the mid and high dose group. These effects were assumed to be non-adverse and adaptive responses as a result of protein sparing effects due to the high levels of MCT intake at 2500 and 3750 mg/kg bw/day. Based on the overall effects of this study, a NOAEL of ≥ 3750 mg/kg bw/day was derived for male and female beagle dogs.

Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol

The subchronic oral toxicity of Modified triglyceride. Main components: 1,3-dioleoyl 2-palmitoyl triacylglycerol and 1,2-dipalmitoyl 3-oleoyl triacylglycerol was investigated in a combined repeated dose, reproductive and postnatal developmental toxicity study in male and female Crl: CD® (SD) BR VAF/Plus rats (Spurgeon, 2003). The test substance was administered daily ad libitum for a period of 24 weeks to groups of 32 animals per sex and dose at dietary concentrations of 1.5, 7.5 and 15%, corresponding to calculated doses of 750, 3750 and 7500 mg/kg bw/day. Two similar constituted control groups were included in the study, either receiving the plain diet (negative control group) or a commercial diet enriched with 15% palm oil (reference oil control group) in order to distinguish between differences due to high oil content in the test diets and differences specifically related to the test material. No treatment-related mortalities were observed during the entire study period. Clinical signs involved pale faecal pellets in the reference oil control and test groups, which were presumably related to high fat content in both diets. No significant differences in body weights were observed between animals of the test groups and the respective control groups. Animals receiving the plain diet (negative control group) showed higher food consumption compared to test groups, but no significant differences in body weights were observed between these groups. Similarly, water consumption was also higher in animals of the negative control group compared to the treatment groups. Haematology analysis in both the reference oil control and treatment groups revealed a shorter clotting time compared to animals receiving the control diet. However, this effect was not considered to be treatment-related, since it occurred both in the test and reference oil control groups. At necropsy, liver findings, including pale, mottled, enlarged, swollen, accentuated lobular markings and, most frequent of all, pale sub-capsular areas, were observed among all groups, and were thus not related to treatment with the test substance. The weights of most organs were reported to be comparable and consistent across all groups. The most consistent difference from the reference oil and negative control groups was a higher absolute ovary weight in the group receiving the test material at 15% in diet. Microscopic examinations revealed a dose-dependent increase in incidence of fat deposition and vacuolation in liver of treated animals compared to the negative control. However, these effects were only slight and not observed in the corresponding F1 generation of the animals, and thus considered to be rather a physiological change than a toxicologically relevant effect. Based on the overall effects of the study, a NOAEL of ≥ 7500 mg/kg bw/day was derived for male and female Crl: CD® (SD) BR VAF/Plus rats.

Repeated dose toxicity, oral, chronic

CAS No. 538-23-8

Oral chronic toxicity of Glycerol trioctanoate was investigated in a GLP-conform study in male Fischer 344/N rats (NTP, 1994). Sixty animals per test group received the undiluted test substance via gavage at dose volumes of 2.5, 5, 10 mL/kg bw/day, corresponding to doses of 2390, 4770, 9540 mg/kg bw/day, as calculated from a density of 0.954 g/mL. A group of 60 animals remained untreated and served as control group. The animals were treated for a period of 104 weeks, except for 10 animals of each group which were already sacrificed after 15 months for interim examinations. A total of 30 animals died or were humanely killed in extremis after treatment with 9540 mg/kg bw/day. Based on these data, the two-year survival rate was significantly lower in animals of the highest dose compared to controls (31/50 survivors in controls vs. 23/53 survivors in the 9540 mg/kg bw/day dose group). Clinical findings of dyspnoea, ataxia and lethargy were observed in 50/60 animals of the high-dose group. Most of the animals generally recovered prior to the next daily dosing and the incidence of clinical findings declined during the second half of the study. However, 8 of 30 rats died between weeks 45 to 49 when the incidence of clinical findings (dyspnoea, ataxia and lethargy) was highest. In addition, these animals revealed a significantly lower body weight than the mean group body weight (316 g vs. 360 g) after 11 months (44 weeks) of treatment. Mean body weights of high dose group animals were decreased when compared to controls throughout the study, although the difference was less than 5% after week 61. A dose-dependent decrease in food consumption was determined, which was most probably due to the fact that rats received more than 10% of their caloric intake from the test item. Thus, the effects on food consumption were considered to be non-adverse. No changes in clinical chemistry parameters were observed in treated animals compared to controls. Significant changes in haematological parameters (increase in the haematocrit, haemoglobin and erythrocyte levels) were only observed in the high dose group when compared to controls. Statistically significant lower absolute kidney weights were only noted in animals of the mid dose (4770 mg/kg bw/day). Since no dose-dependency occurred, these effects were considered to be incidental and not treatment-related. No adverse effects were reported at gross pathology. Histopathological examination revealed a significant decrease in the incidence of nephropathy between animals of the high dose group and controls, which was due to the lower protein intake as a result of lower food consumption A dose-related increase in the incidences of pancreatic exocrine hyperplasia and adenoma as well as proliferative lesions of the forestomach was observed in the treated animals. Based on the results of this study, the NOAEL for male Fischer 344/N rats was set at 4770 mg/kg bw/day.

CAS No. 736150-63-3

A 52-week chronic oral toxicity study with Glycerides, castor-oil, mono, hydrogenated, acetates was performed in Wistar HsdHan™:WIST rats according to OECD guideline 452 and in compliance with GLP (Dunster, 2011). The animals (21 per sex and dose) were exposed daily to the test substance at dietary concentrations of 1500, 6000 and 15000/25000 (from Week 10)/30000 (from Week 41) ppm, corresponding to mean achieved dose levels of 98, 392 and 1333 mg/kg bw/day in males and females, respectively. A control group, consisting of 21 animals per sex, received diets enriched with Arachis oil to achieve comparable calorific intake than treated animals. On Day 280, one unscheduled death occurred in one male animal of the high dose group which showed multifocal necrosis in the liver as well as acanthosis and hyperkeratosis of the forestomach. As no further deaths occurred and the findings were not confirmed at scheduled sacrifice in any treated animal, the cause of mortality was not related to treatment. Furthermore, there were no toxicologically significant clinical signs and neurobehavioural changes detected throughout the treatment period. The overall bodyweight gain for all treatment groups was comparable to controls.There were no treatment-related effects on food consumption or food efficiency in the animals of any dose group compared to controls. Urinalysis did not show any treatment-related effects on the parameters examined. Changes in clinical chemistry and haematological parameters in males were not dose-related and therefore considered to be not toxicologically relevant. Absolute and relative organ weights of kidneys in both sexes and thyroid/parathyroid glands in females among different dose groups were increased. Since no dose-dependency and no histopathological correlates in these organs were observed, the effects were considered not to be of toxicological relevance.. At macroscopic examination, no treatment-related findings were observed in animals of any dose group. All other lesions observed were considered to be incidental and characteristic for aging animals of this strain. Histopathology did not reveal any substance-related effects in the treated animals. All morphological findings were those commonly observed in rats of this age and strain. Based on the results of this study, the NOAEL for male and female Wistar HsdHan™:WIST rats was established at ≥1333 mg/kg bw/day.

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

In a chronic oral study investigating the effects of long-term exposure to medium chain triglycerides (MCT) on growth, the test substance was administered daily at a limit concentration of 19.6% via diet to 15 male and female Wistar rats each for a period of 47 weeks, corresponding to a dose level of approximately 9800 mg/kg bw/day assuming a food intake of 50 g/kg bw/day (Harkins and Sarett, 1968). Two similar constituted control groups either received 21% safflower oil or 21% corn oil as dietary fats. In addition, three further groups consisting of 15 animals per sex were treated with diets containing conventional dietary fats (18.5% oleo oil, butter fat or coconut oil, respectively) and served as positive controls. During the study period, three males and two females died in the group receiving the diet containing MCT. However, no marked differences in mortality were observed between the MCT group and the other dietary fat groups. Body weight gain in animals of the MCT group was moderately lower compared to the groups receiving other dietary fats. A significant difference was only observed between the body weight gain of males from the MCT group and males of the coconut oil group. The weights of liver, kidney, spleen, heart, adrenals, femurs, and testes were similar between all tested groups and no gross pathological lesions were observed at necropsy. Epididymal fat pads showed lower absolute and relative weights in the MCT group compared to groups receiving the other dietary fats (statistically significant difference between MCT and coconut oil group). At histopathology, no differences in MCT-treated group compared to the groups receiving the other dietary fats were observed. Total plasma cholesterol levels after 7, 14, 21 and 35 weeks were lower in male rats receiving the MCT diet compared to the rats fed with other dietary fats. In females, no effects on total plasma cholesterol were observed during these measurement intervals. At study termination, MCT values were similar or higher compared to the other groups and were not considered to be of toxicological relevance. Levels of total lipids, cholesterol and the fraction of triglycerides in liver were lower in animals on the MCT diet compared to those receiving the other dietary fats. Phospholipid levels were not affected by the type of dietary fat administered to the animals. Other investigations including caloric efficiency, dietary and epididymal fat composition and net absorption of dietary fat, protein and calcium showed no effects of toxicological relevance. Based on the study results, the level for no adverse effects in male and female Wistar rats was set at a concentration of 19.6% (ca. 9800 mg/kg bw/day) of the test substance in the diet.

Mixture of mono-, di-, and triglycerides of lauric acid

A chronic feeding study in rats with a mixture of mono-, di-, and triglycerides of lauric acid was performed in male and female Osborne-Mendel rats at a dietary concentration of 25%, corresponding to calculated dose levels of 10000 and 12500 mg/kg bw/day in males and females, respectively (Fitzhugh, 1960). Twenty-four animals per sex received the test substance daily ad libitum for a period of 2 years. Two similar constituted groups of animals were administered the plain diet or hydrogenated cottonseed oil at 25% in the diet, respectively, and served as controls. After 2 years exposure to the test substance via the diet, no significant differences in the total number of mortalities in the dose group compared to the groups fed either hydrogenated vegetable oil or the basal diet was observed. There was no significant difference in weight gains after 26 or 52 weeks between treated animals and the control group receiving hydrogenated cottonseed oil. However, weight gains were greater in animals treated with the test substance compared to those fed the basal diet, which corresponded to the higher caloric intake of treated animals and animals of the control group receiving hydrogenated cottonseed oil. No gross pathology findings attributable to treatment with the test substance were observed at necropsy of the animals compared to the control groups. Detailed histological examination of all three groups of rats revealed a slight excess of hepatic cell fatty change as the only effect compared to only a small effect observed in the controls fed with basal diet. However, the effects in the treatment group only occurred at incidences not greater than those observed in the control group fed the hydrogenated cottonseed oil. A similar correlation, but to a lesser degree, was also observed for intrahepatic bile duct proliferation in treated animals and control animals administered the hydrogenated cottonseed oil. Based on the results of this study, the NOAEL for Osborne-Mendel rats was established at 10000 and 12500 mg/kg bw/day for males and females, respectively.

CAS No. 56-81-5

The chronic oral toxicity of Glycerol was investigated in a two-year feeding study in male and female Long-Evans rats (Hine et al., 1953). Natural or synthetic glycerine was administered 7 days/week ad libitum for a period of 105 weeks to groups of 22 animals per sex at dietary concentrations of 5 and 10, corresponding to calculated doses levels of 2500 and 5000 mg/kg bw/day, respectively. A control group of 26 animals received the plain diet. A further treatment group of 22 animals per sex was included in the study, which received natural or synthetic glycerine for a period of 52 weeks at a dietary concentration of 20%, corresponding to 10000 mg/kg bw/day. No information on mortalities and clinical signs was provided. Body weights and body weight gains in treated animals of all dose groups were comparable to those of controls. A slight (statistically significant) increase in food consumption was reported for males fed 5 and 10% of natural test substance, in comparison with the corresponding group administered the synthetic test substance. Haemoglobin determinations conducted after 3, 6, 12, 18 and 24 months of treatment did not demonstrate any difference between control and test groups. At urinalysis, a high incidence of albuminuria was reported among all dose groups and was also found at high incidence in the control group. Due to the random distribution and wide variation in degree of albuminuria throughout the experimental groups, no significance could be attributed to these effects. Statistically significant increases and decreases in relative organ weights of liver, lung, heart, kidney and spleen were incidentally observed in almost all treatment groups compared to controls. Since there was no apparent relationship to treatment, these changes were not considered to be toxicologically relevant. At necropsy, no gross lesions attributable to treatment were noted. At histopathological examination, non-neoplastic findings involved inflammatory lesions in a total of 27 animals evenly distributed among groups. The most frequent abnormalities were bronchiectasis, pneumonia and pulmonary abscesses. Taenia infestation of the liver was rarely observed. In several animals, hydronephrosis and pyelonephritis were noted. Neoplastic lesions involved the incidence of malignant and benign tumours in almost all groups (control and treatment) without clear evidence for a treatment-related increase in the incidence of neoplastic lesions. The determination of glycogen and lipid content in the liver did not reveal any differences between animals given 20% natural and synthetic glycerine for a period of 52 weeks. However, the relevance of these findings was unclear as no control values were available. Based on the overall effects of the study, a NOAEL of ≥ 10000 mg/kg bw/day was derived for male and female Long-Evans rats.

 

Repeated dose toxicity, dermal, subacute and subchronic

CAS 73398-61-5

A subchronic dermal repeated dose toxicity study was performed with Triglycerides, mixed decanoyl and octanoyl in female rats (Elder, 1980). A perfumed skin softener formulation containing 4% Caprylic/Capric Triglyceride was applied to the shaved skin of 15 female rats at a dose of 2 mL/kg five days per week for 13 weeks, equivalent to 75 mg/kg bw/day. This treatment had no effects on the body weight, clinical appearance or behaviour. All blood-cell and serum chemistry parameters measured one week before termination of the study were within normal limits and comparable to those seen in an equal group at controls. At necropsy, organ weights and gross finding revealed no effects of the test substance, and no histopathological changes were observed. There were no localized effects on the skin. Based on this study results the subchronic dermal NOAEL for female rats was found to be 75 mg/kg bw/day (highest dose tested, 4% of the test substance in formulation).

An additional study with a tanning butter formulation containing 22% Caprylic/Capric Triglyceride was applied to the clipped backs of three male and three female New Zealand stain albino rabbits at a dose of 2000 mg/kg bw five times per week for 28 days (Elder, 1980). Throughout the test, no effects attributable to the treatment were noted on body weight, physical appearance and behaviour. Blood samples taken 23 days after initiation of the test showed no effects on haematocrit, haemoglobin concentration, cell counts, urea nitrogen, alkaline phosphatase or glutamic pyruvic transaminase activites, or glucose concentration. At the end of the test, no systemic, gross or histopathologic changes referable to the test material were observed. On the treated area of the skin there was slight to moderate erythema and slight peeling and cracking regardless of whether the skin was abraded or left intact. Based on the study results a subacute (28-day) dermal NOAEL of 2000 mg/kg bw/day for the tanning butter formulation containing 22% Caprylic/Capric Triglyceride was found for male and female rabbits.

However, only a single dose was tested in both studies and only basic data very provided, which do not allow a complete assessment of the potential subacute and subchronic dermal repeated dose toxicity of glycerides, mixed decanoyl and octanoyl. Therefore, the results of both studies were not further taken into account for hazard assessment of repeated dose toxicity of the substance via the dermal route.

Overall conclusion for repeated dose toxicity

The available data on the repeated dose oral toxicity of Glycerides comprise a number of subacute, subchronic and chronic studies in rats, mice and dogs. Available data from surrogate substances including the hydrolysis products glycerol and docosanoic acid are likewise taken into account for assessment. Adverse effects (if any) have only been reported in studies in which animals have been given high doses of the test substance. Nevertheless, in all available studies NOAEL values for oral repeated dose toxicity were all at or well above the currently applied limit dose value of 1000 mg/kg bw/day. Thus, no hazard after repeated oral exposure was identified.

Similarly, no effects were observed in subacute and subchronic dermal repeated dose toxicity studies with the category member glycerides, mixed decanoyl and octanoyl (73398-61-5). However, as only basic data were provided in these studies and only single doses of the diluted test substance were applied, these data were not taken into account for hazard assessment of repeated dose toxicity via the dermal route.

Based on the available data and following the category approach, all members of the Glycerides category are considered to have no long-term toxic effect by the oral route.

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 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.