Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral: LD50 > 5000 mg/kg bw 
Inhalation: LC50 > 1.86 mg/L
Dermal: LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 - 26 Dec 1988
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Comparable to guideline study with acceptable restrictions. Only 5 males were used in the limit test, the observation period was 7 days. no gross pathology examination was performed, the mouse was used instead of the preferred species the rat, the test substance purity was not specified.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted Feb 1987
Deviations:
yes
Remarks:
only 5 males were used in the limit test, no gross pathology examination was performed, observation period was 7 days, the mouse was used instead of the preferred species the rat, the test substance purity was not specified
Qualifier:
according to guideline
Guideline:
other: Pharmacopée Franҫaise IXe édition
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
mouse
Strain:
other: NMRI Han EOPS
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: EVIC CEBA, Blanquefort, France
- Weight at study initiation: on average 20 g
- Fasting period before study: approximately 4 h
- Housing: animals were housed in groups of 5 in polypropylene cages (46.5 x 15.5 x 14 cm)
- Diet: UAR 113 pellets, ad libitum
- Water: tapwater, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): minimum 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
5 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: The animals were observed for mortality and clinical signs during 2 hours after administration and twice daily thereafter during the study period; the body weight was recorded prior to administration and on day 7 prior to sacrifice
- Necropsy of survivors performed: no
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: No clinical signs of toxicity were observed up to the end of the 7-day observation period.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given (comparable to guideline study).
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
only male animals tested; lack of details on test substance
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Willi Gassner, Sulzfeld, Germany
- Weight at study initiation: approximately 170 g
- Housing: 2 animals per Makrolon Type 3 cage with Vermiculite pad
- Diet: standard pelled diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 60 ± 5
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindric inhalation chamber "INBIFO-MAKROLON-Tierrohre Typ 1" with stainless steel head cones, according to KIMMERLE apparatus with 20 animal tubes
- Exposure chamber volume: 40 L
- Method of holding animals in test chamber: cylindric tube
- Source and rate of air: 7.11 L air flow/min
- Method of conditioning air: 0.2 mL of test substance per min was pumped using a dosing pump (BRAUN, Melsungen, Germany)
- System of generating particulates/aerosols: aerosol nozzle, nozzle orifice 0.15 mm (BUNDSCHUH, Griesheim, Germany)
- Measured test substance concentration in inhalation chamber: 28.1 µL/ L air

"Zyklon" (BCRIA sampler) was used to sample precipitated particles with a particle size > 5 µm
A cambridge filter was used to sample respirable particles.
Gravimetric analyses were performed to determine the respirable test substance concentration.

TEST ATMOSPHERE
- Brief description of analytical method used: during exposure every hour the aerosol concentration was measured in the inhalation chamber directly in the area of animals noses (head cones)
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.97 µL test substance / L air was < 5 µm diameter
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Gravimetric analyses were performed to determine the respirable test substance concentration.
Duration of exposure:
6 h
Concentrations:
28.1 µL/L air (calculated concentration)
measured respirable test substance concentration: 1.97 µL/ L air (< 5 and < 10 µm diameter particle size)
No. of animals per sex per dose:
10
Control animals:
other: yes, sham-exposed
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: during exposure, after exposure and thereafter daily
- Frequency of weighing: at beginning, directly after exposure and at the end of 14 days observation period
- Necropsy of survivors performed: yes, 3 test animals and 1 control animal were euthanized 1 h after exposure, all other animals were necropsied 14 days after exposure
- Other examinations performed: Trachea and lungs of all animals were histopathologically analysed.
Sex:
male
Dose descriptor:
LC50
Effect level:
> 1.97 other: µL/L air (analytical)
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: max. attainable concentration
Sex:
male
Dose descriptor:
LC50
Effect level:
> 1.86 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: converted from µL/L by using a mean specific gravity value of 0.947
Mortality:
No mortality occured during the study period.
Clinical signs:
other: No clinical signs toxicity were observed in any of the animals during the 14-day observation period.
Body weight:
No effect on body weight was noted.
Gross pathology:
No abnormal findings.
Other findings:
Histopathology: No abnormal findings in lungs or tracheae.
Microscopically no deposits of oily test substance could be detected in the respiratory tissues.

According to the descriptions in this study report it can be assumed that the maximum attainable concentration of the test substance was used for aerosol inhalation exposure.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable (Klimisch score 2) study from a reference substance 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).
The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
22 Mar - 07 Apr 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP-Guideline study, tested with the source substance Propane-1,2,3-triyl trisheptanoate (CAS 620-67-7). 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-aross substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted in 1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Bor: WISW
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Weight at study initiation: 250-260 g (males), 209-238 g (females)
- Housing: up to 5 animals per cage in Makrolon type III
- Diet: Ssniff R 10 - Complete feed for rats (Ssniff, Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsum
- % coverage: 10%
- Type of wrap if used: gauze and acrylastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: residual test material was removed with warm water and gauze
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2.08 cm³/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on Day 0, thereafter daily
- Frequency of weighing: Days 0, 7 and 14
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
other: No signs of systemic toxicity observed.
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
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies from 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).
The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for read-across

Data on the acute inhalation and dermal toxicity of glyceryl undecylenate (CAS 123759-97-7) are not available. The assessment of acute toxicity was therefore based on studies conducted with the target substance and with source substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Acute oral toxicity

CAS 123759-97-7

In an acute oral toxicity study performed according to protocol similar to OECD guideline 401, 5 male NMRI mice were administered 5000 mg/kg bw glyceryl undecylenate by gavage (Catroux, 1988). No mortality occurred, and no clinical signs were observed in the animals during the 7-day observation period. The increase in body weight was within the normal range reported for animals of this strain. Therefore, the oral LD50 value for male mice is > 5000 mg/kg bw.

Acute inhalation toxicity

CAS No. 73398-61-5

The acute inhalation toxicity of triglycerides, mixed decanoyl and octanoyl was assessed according to OECD guideline 403 and in compliance with GLP (Reminghaus, 1976). A group of 10 male rats was exposed to a calculated concentration of 28.1 µL/L air for 6 h using a nose-only exposure system. The measured respirable test substance concentration was 1.97 µl/L (particles with a diameter below 10 µm), corresponding to an atmosphere concentration of the test aerosol of 1.86 mg/L. This was considered to be 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, or during the 14-day observation period. The body weight 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 air (analytical).

Acute dermal toxicity

CAS 620-67-7

The acute dermal toxicity potential of Glycerol triheptanoate was assessed in a study performed according to OECD guideline 402 and in compliance with GLP (Mürmann, 1993). Five rats/sex were dermally exposed to the test substance at a limit dose of 2000 mg/kg bw. The undiluted test substance was applied to the shaved skin of the test animals for 24 h under semiocclusive conditions. After the exposure period, residual test substance was removed and the 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. All the rats showed the expected gain in body weight throughout the study. During 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 91845-19-1

The dermal effects of Glycerides, C16-18 and C18-hydroxy mono- and di- were investigated in an acute dermal toxicity study performed according to a protocol similar to OECD guideline 402 and in compliance with GLP (Potokar, 1985). In a limit test, 2000 mg/kg bw of the undiluted test substance was applied to the shaved skin of 5 rats/sex for 24 h under occlusive conditions. After the exposure period, residual test substance was removed and the animals were observed for a period of 14 days. No mortality occurred and no clinical signs were observed during the observation period. Male and female rats showed the expected gain in body weight. The necropsy and histopathological examination did not reveal any substance-related findings. One male and two female animals showed a reddening of the ileum mucosa, which was not considered to be treatment-related. No local skin effects were observed. The dermal LD50 value for male and female rats is considered to be > 2000 mg/kg bw.

 

Overall conclusion for acute toxicity

The reliable data available for the target and source substances indicate a very low level of acute toxicity following the oral, inhalation and dermal route, as LD50 values were greater than the currently applied limit values and the LC50 value was the maximum attainable value. Therefore, as the available data did not identify any hazard for acute toxicity, glyceryl undecylenate is not considered to be hazardous following acute exposure.


Justification for selection of acute toxicity – oral endpoint
The reliable study was selected.

Justification for selection of acute toxicity – inhalation endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is most adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance 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 a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between the source and target substance 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 glyceryl undecylenate (CAS 123759-97-7), data will be generated from information available on reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

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