Registration Dossier

Administrative data

Description of key information

The substance 1,2,3 -Propanetricarboxylic acid, 2 -hydroxy-, tris(C12 -13-branched-alkyl) ester is practically non-toxic after acute exposition.
LD50 oral > 5000 mg/kg
LD50 dermal > 2000 mg/kg
This supported by studies of similar substances.

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:
June 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions, read-across.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Morino - S. Polo d'Enza (RE), italy
- Age at study initiation: not mentioned
- Weight at study initiation: 200 - 330 g (males: 306 ± 17.0 g, females: 225 ± 15.4 g)
- Fasting period before study: not mentioned
- Housing: in groups of five of the same gender in transparent polycarbonate cages (dimensions 425x266x180 mm)
- Diet: standard pellet complete diet ad libitum
- Water: filtered tap water from local network ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 25
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1992-06-02 To: 1992-06-16
Route of administration:
oral: gavage
Vehicle:
other: sesame seed oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 500 mg/ml
- Justification for choice of vehicle: sesame seed oil is non-toxic to used species
- Purity: not mentioned

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg b.w.
Doses:
5000 mg/kg b.w.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (5 days out of 7)
- Frequency of observations and weighing: daily observations of mortality, organic body functions, tegumentary apparatus, mucosae conditions, somamotor activity and sensorium conditions, weighing before the experiment, after 7 days and at the end of the study
- Necropsy of survivors performed: yes
Statistics:
not performed
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study.
Clinical signs:
No clincial symptoms were observed related to treatment.
Body weight:
Body weight gain was normal for the species and strain used in the study.
Gross pathology:
At the ante-mortem and post-mortem the animals showed no pathologic symptoms. Nothing abnormal was found in the autopsy on animals.
Interpretation of results:
GHS criteria not met
Conclusions:
In these experimental conditions the test material Cosmacol ECI did not provoke toxic effects. The LD 50 was greater than 5000 mg/kg body weight.
Executive summary:

An acute oral toxicity test was carried out on a group of 10 rats (5 male and 5 female) using Cosmacol ECI. The test material was administered at a dose of 5000 mg/kg oral by gavage. During the study the animals were observed daily for 14 days (5 out of 7) for signs of possible toxic symptoms and mortality. Body weight was noted weekly. At the end of the study necropsy was performed on all animals.

None of the animals died during the course of the study, no clincial symptoms were observed that could be related to treatment, the body weight gain was normal for the species and strain. At necropsy the animals showed no pathological symptoms or abnormalities ante- and post-mortem.

The test material Cosmacol ECI did not provoke toxic effects under the experimental conditions described and the LD50 was judged to be greater than 5000 mg/kg b.w.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
Klimisch 2

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
November 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with national standard methods with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: "Nossan" - Correzzana MI - ITALY
- Age at study initiation: no data
- Weight at study initiation: 180 - 200 g
- Fasting period before study: no data
- Housing: groups of 5 of the same sex in transparent polycarbonate cages (dimensions mm 425X266X180)
- Diet: standard pellet complete diet supplied by the breeder
- Water: Filtered tap water from local network ad libitum
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 25
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1993-11-17 To: 1993-12-1
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area
- % coverage: no data
- Type of wrap if used: The sample was put on a patch (Hansamed strips), the patch was then covered by an impermeable and hypoallergenic plastic adhesive tape (Blenderm 3M)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
Duration of exposure:
24 h
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: General conditions of the animals were controlled after 2, 6 and 24 h and daily thereafter for 14 days, observations included: mortality, clinical signs and behaviour (somatic motor activity, tegumentary apparatus, mucosae conditions, respiratory activity, sensorium conditions), weighing before the experiment, after 7 days and at the end of the study
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred during the study.
Clinical signs:
No clinical signs were observed.
Body weight:
Body weight gain was normal during the study.
Gross pathology:
No pathological symptoms were observed, no macroscopic abnormalities were seen at ante-mortem and post-mortem examination.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 was higher than 2000 mg/kg.
Executive summary:

The study was performed on a group of ten rats (5 male and 5 female). The test material was administered undiluted at a dose of 2000 mg/kg by dermal application under occlusive conditions for a exposure period of 24 hours. The animals were observed for 14 days thereafter. There were no deaths during the study. No clinical signs were detected during the experimental observation period. Body weight gain was considered normal for the species and strain of rats used in this study. No macroscopic abnormalities were seen at necropsy. The LD50 was higher than 2000 mg/kg. The results of the study indicate that the test material, 1,2,3 -Propanetricarboxylic acid, 2 -hydroxy-, tris(C12 -13 -branched-alkyl) ester can be considered practically non toxic.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Klimisch 2

Additional information

The LD50 oral of the test substance 1,2,3 -Propanetricarboxylic acid, 2 -hydroxy-, tris(C12 -13 -branched-alkyl) ester

was > 5000 mg/kg. This result was supported with data available from three different studies on analogues demonstrating a lack of toxic effects up to doses far above the limit dose as recommended by current regulatory guidelines. No mortalities or any toxic effects in rats after administration of doses up to 5000 mg/kg were observed.

The LD50 dermal of the test substance 1,2,3 -Propanetricarboxylic acid, 2 -hydroxy-, tris(C12 -13 -branched-alkyl) ester

was > 2000 mg/kg. This result was supported with data available from two different studies of analogues demonstrating a lack of toxic effects up to doses far above the limit dose as recommended by current regulatory guidelines. The substance 1,2,3 -Propanetricarboxylic acid, 2 -hydroxy-, tris(C12 -13 -branched-alkyl) ester has very low vapor pressure (< 0.1 Pa at 25 °C), so the potential for the generation of inhalable forms is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Furthermore rhe results of laboratory animal studies show low acute oral and dermal toxicity for the related substance Tri (hexyl, octyl, decyl) citrate. This intrinsic property/toxicity potential can be extrapolated to acute inhalative route administration.

Justification for selection of acute toxicity – inhalation endpoint
The substance 1,2,3 -Propanetricarboxylic acid, 2 -hydroxy-, tris(C12 -13-branched-alkyl) ester has very low vapor pressure (< 0.1 Pa at 25 °C), so the potential for the generation of inhalable forms is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Furthermore the results of laboratory animal studies show low acute oral and dermal toxicity for the test substance and all similar substances. This intrinsic property/toxicity potential can be extrapolated to acute inhalative route administration.

Justification for classification or non-classification

The substance 1,2,3 -Propanetricarboxylic acid, 2 -hydroxy-, tris(C12 -13 -branched-alkyl) ester is practically non-toxic after acute exposition with a LD50 oral > 5000 mg/kg and LD50 dermal > 2000 mg/kg.

No classification for acute toxicity is indicated according to the classification, labeling and packaging (CLP) regulation (EC) No 1272/2008.