Registration Dossier

Administrative data

Description of key information

Oral: LD50 > 2000 mg/kg bw 
Dermal: LD50 > 2000 mg/kg bw
Inhalation: no data

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 Dec 2009 - 05 Jan 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP-Guideline study, tested with the source substance glycerides, C8-18 and C18-unsatd. mono- and di-, acetates (CAS 91052-13-0). According to the ECHA guidance document ‘Practical guide 6: How to report read-across and categories' (ECHA, 2012), the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No. 8147, November 2000
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: young adult animals (approx. 9-10 weeks old)
- Weight at study initiation: 160-190 g, body weight variation did not exceed ± 20% of the sex mean
- Fasting period before study: animals were deprived of food overnight prior to dosing and until 3-4 h after administration of the test substance, water was available
- Housing: group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, UK).
- Diet: pelleted rodent diet (SM R/M-Z from SSNlFF® Spezialdiaten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 (actual range: 18.4- 21.8)
- Humidity (%): 40-70 (actual range: 31 - 88)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: the vehicle was selected based on trial formulations performed at the testing labotatory and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: according to OECD guideline 423
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality: twice daily; clinical observations: daily; bodyweight: Day 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: According the OECD test guideline 423, Annex 2b, the LD50 was considered to exceed 5000 mg/kg body weight.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Hunched posture and/or piloerection was observed among all females on Day 1.
Body weight:
The body weight gain of the treated animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-03-25 to 1996-04-11
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP guideline study, tested with the source substance glyceryl citrate/lactate/linoleate/oleate (CAS 91744-23-9). According to the ECHA guidance document ‘Practical guide 6: How to report read-across and categories' (ECHA, 2012), the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adult
- Weight at study initiation: 146 - 161 g (male); 130 - 142 g (female)
- Fasting period before study: 16 hours
- Housing: 1 - 5 animals in Makrolon cages, type III
- Diet (e.g. ad libitum): R10 Complete feed for rats ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk, Haltern, Germany
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.004 cm³/kg
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Examination of clinical signs up to 6 hours after the treatment and daily observations thereafter; bodyweights were determined before treatment (day 0), and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
no statistics performed
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Mortality:
0/10 animals
Clinical signs:
none
Body weight:
normal body weight gain of all animals
Gross pathology:
no findings
Other findings:
none
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD0 of was greater than 2000 mg/kg bodyweight. No clinical symptoms occurred.
Executive summary:

The acute oral toxicity of the test substance CAS 91744-23-9, Glyceryl Citrate/Lactate/Linoleate/Oleate) to male and female Sprague-Dawley rats was investigated in a OECD 401 limit test under GLP conditions. The test substance was given to five animals per sex in a single dose of 2000 mg/kg bw.

Animals were examined for clinical signs up to 6 hours after the treatment. Thereafter, animals were daily observed for 14 consecutive days; bodyweights were determined before treatment (day 0), and 7 and 14 days after treatment. At the end of the 14 day observation period all animals were subject to necropsy.

During the study none of the animals died and animals did also not show clinical signs. Body weight gain was normal for all animals. Gross pathology did not result in any findings. Therefore, it can be concluded that the substance is practically non-toxic (LD50 > 2000 mg/kg bw).

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Reason / purpose:
read-across source
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: young adult animals (approx. 9-10 weeks old)
- Weight at study initiation: 160-190 g, body weight variation did not exceed ± 20% of the sex mean
- Fasting period before study: animals were deprived of food overnight prior to dosing and until 3-4 h after administration of the test substance, water was available
- Housing: group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, UK).
- Diet: pelleted rodent diet (SM R/M-Z from SSNlFF® Spezialdiaten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3 (actual range: 18.4- 21.8)
- Humidity (%): 40-70 (actual range: 31 - 88)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: the vehicle was selected based on trial formulations performed at the testing labotatory and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: according to OECD guideline 423
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality: twice daily; clinical observations: daily; bodyweight: Day 1, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: According the OECD test guideline 423, Annex 2b, the LD50 was considered to exceed 5000 mg/kg body weight.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Hunched posture and/or piloerection was observed among all females on Day 1.
Body weight:
The body weight gain of the treated animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Necropsy revealed no substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
refer to category justification report provided in IUCLID section 13
Reason / purpose:
read-across source
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adult
- Weight at study initiation: 146 - 161 g (male); 130 - 142 g (female)
- Fasting period before study: 16 hours
- Housing: 1 - 5 animals in Makrolon cages, type III
- Diet (e.g. ad libitum): R10 Complete feed for rats ad libitum, supplied by Ssniff Spezialfutter GmbH, Soest, Germany
- Water (e.g. ad libitum): Drinking water ad libitum, supplied by Gelsenwasser, Wasserwerk, Haltern, Germany
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.004 cm³/kg
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Examination of clinical signs up to 6 hours after the treatment and daily observations thereafter; bodyweights were determined before treatment (day 0), and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
no statistics performed
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Mortality:
0/10 animals
Clinical signs:
none
Body weight:
normal body weight gain of all animals
Gross pathology:
no findings
Other findings:
none
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD0 of was greater than 2000 mg/kg bodyweight. No clinical symptoms occurred.
Executive summary:

The acute oral toxicity of the test substance CAS 91744-23-9, Glyceryl Citrate/Lactate/Linoleate/Oleate) to male and female Sprague-Dawley rats was investigated in a OECD 401 limit test under GLP conditions. The test substance was given to five animals per sex in a single dose of 2000 mg/kg bw.

Animals were examined for clinical signs up to 6 hours after the treatment. Thereafter, animals were daily observed for 14 consecutive days; bodyweights were determined before treatment (day 0), and 7 and 14 days after treatment. At the end of the 14 day observation period all animals were subject to necropsy.

During the study none of the animals died and animals did also not show clinical signs. Body weight gain was normal for all animals. Gross pathology did not result in any findings. Therefore, it can be concluded that the substance is practically non-toxic (LD50 > 2000 mg/kg bw).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common precursors and breakdown products of hydrolysis and consistent trends in environmental fate, ecotoxicological and toxicological profile (refer to the endpoint discussion for further details).

Additional information

Justification for read-across

Reliable data on the acute oral, inhalation and dermal toxicity of glycerides, C16-18 and C18-unsaturated, mono-and di-citrates (CAS 91052-16-3) are not available. The assessment of acute toxicity by the oral and dermal route was therefore based on studies conducted with analogue substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity

CAS 91052-13-0

The acute oral toxicity of glycerides, C8-18 and C18-unsatd. mono- and di-, acetates was investigated in an OECD guideline 423 study under GLP conditions (Otterdijk, 2010a). In this study, female Sprague Dawley rats were exposed to a limit dose of 2000 mg/kg bw in a stepwise procedure (3 rats per step). 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.

CAS 91744-23-9

The acute oral toxicity of glyceryl citrate/lactate/linoleate/oleate to male and female Sprague-Dawley rats was investigated in an OECD 401 limit test under GLP conditions (Kruegar, 1996a). The test substance was given to five animals per sex in a single dose of 2000 mg/kg bw. Animals were examined for clinical signs up to 6 hours after the treatment. Thereafter, animals were daily observed for 14 consecutive days; bodyweights were determined before treatment (day 0), and 7 and 14 days after treatment. At the end of the 14 day observation period all animals were subject to necropsy.During the study none of the animals died and animals did also not show clinical signs. Body weight gain was normal for all animals. Gross pathology did not result in any findings. Therefore, it can be concluded that the substance is practically non-toxic (LD50 > 2000 mg/kg bw).

Acute dermal toxicity

CAS 91052-13-0

The acute dermal toxicity of glycerides, C8-18 and C18-unsatd. mono- and di-, acetates was investigated in a limit test according to OECD guideline 402 and in compliance with GLP (Otterdijk, 2010b). 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 91744-23-9

The acute dermal toxicity of glyceryl citrate/lactate/linoleate/oleate to male and female Sprague-Dawley rats was investigated in an OECD 402 limit test under GLP conditions (Kruegar, 1996b). The test substance was applied to the skin of five animals per sex in a single dose of 2000 mg/kg bw (semi-occlusive coverage). Total exposure was for 24h. Thereafter, the test substance was removed using warm water and cellulose. Animals were examined for clinical signs 0.5, 1, 2, 3, 4, 5 and 6 hours after treatment. Animals were thereafter daily observed for 14 consecutive days; bodyweights were determined before treatment (day 0), and 7 and 14 days after treatment. At the end of the 14 day observation period all animals were subject to necropsy. During the study none of the animals died and animals did also not show clinical signs. Body weight gain was normal for all animals. Gross pathology did not result in any findings. Therefore, it can be concluded that the substance is practically non-toxic (LD0 > 2000 mg/kg bw).

Overall conclusion for acute toxicity

The reliable data available for the read-across analogue substances indicate a very low level of acute toxicity following the oral and dermal route, as LD50 values were greater than the currently applied limit values. Therefore, as the available data did not identify any hazard for acute toxicity, glycerides, C16-18 and C18-unsaturated, mono-and di-citrates (CAS 91052-16-3) is not considered to be hazardous following acute exposure.


Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to glycerides, C16-18 and C18-unsaturated, mono-and di-citrates (CAS 91052-16-3) data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.Therefore, based on the analogue read-across approach, the available data on acute toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.