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Description of key information

The oral toxicity of the substances was investigated according to OECD Guideline 401 in a read across approach. The test substance did not cause toxic symptoms in doses up to 50000 mg/kg b.w.

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:
from 1997-06-23 to 1997-08-25
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study, read-across
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland GmbH, Sulzfeld, Germany
- Age at study initiation: 39 days (males); 48 days (females)
- Weight at study initiation: 164 - 200 g (males); 155 - 184 g (females)
- Fasting period before study: approx. 16 hours
- Housing: in groups of 2 - 3 animals in Makrolon cages type III on granulated textured wood bedding
- Diet (e.g. ad libitum): Altromin 1324 (Standard diet for rats and mice) ad libitum, supplied by Altromin GmbH, Lage/Lippe, Germany
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 60 ± 20
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
other: 0.8 % aqueous hydroxypropylmethylcellulose gel (METHOCEL E 4 M, Synopharm, Barsbüttel, Germany)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: The test substance was diluted to the appropriate concentration for dose levels 1 - 4 (2000, 6000, 10000 and 20000 mg/kg), for group 5 (50000 mg/kg) the test substance was used as supplied), no further details mentioned.
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: not justified
- Lot/batch no. (if required): MM90100512E
- Purity: no data


MAXIMUM DOSE VOLUME APPLIED: group 1 - 4: 20 mL/kg bw; group 5: 50 mL/kg bw
Doses:
2000 / 6000 / 10000 / 20000 / 50000 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: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 h after administration and thereafter daily. Individual boy weights were recorded before administration of the substtance , thereafter in weekly intervalls.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs concerning changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern were examined, attention was also paid to possible tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Statistics:
No statistics performed, due to lack of mortality in this study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 50 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality occurred
Clinical signs:
no clinical signs observed
Body weight:
normal body weight gain achieved
Gross pathology:
no test substance related findings noted

Table: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]

 

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity(#/total)

Male

Female

Combined

Male

Female

Combined

2000

 0/5

 0/5

 0/10

 -

 0/5

 0/5

 0/10

6000

 0/5

 0/5

 0/10

 -

 0/5

 0/5

 0/10

10000

 0/5

 0/5

 0/10

 -

 0/5

 0/5

 0/10

20000

 0/5

 0/5

 0/10

 -

 0/5

 0/5

 0/10

50000

 0/5

 0/5

 0/10

 -

 0/5

 0/5

 0/10

 

Interpretation of results:
GHS criteria not met
Conclusions:
Under the present test condition a single oral administration of up to 50000 mg/kg b.w. to rats revealed no toxic symptoms. 50000 mg/kg equivalent to an application volume of 50 mL/kg was the highest reasonable application volume. The test substance was classified to be relatively non-toxic.
Executive summary:

The test item was investigated according to OECD Guideline 401. The test subsatnce was administered to once orally to male and female Sprague-Dawley rats by gavage a doses up to 50000 mg/kg b.w. Subsequently, observations of effects and deaths were made. All surviving animals were observed for a period of 14 days.

Under the present test condition a single oral administration of up to 50000 mg/kg b.w. to rats revealed no toxic symptoms. 50000 mg/kg equivalent to an application volume of 50 mL/kg was the highest reasonable application volume. The test substance was classified to be relatively non-toxic.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read across is based on the hypothesis that source and target substance have similar toxicological and ecotoxicological properties, because
- they are manufactured from similar/identical precursors under similar conditions
- they share structural similarities with common functional groups: ester bonds and fatty alcohol chains varying in length

Therefore, read across from the existing physical-chemical, toxicological and ecotoxicological studies on the source substance is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance , in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source substance 2-Hydroxypropan-1,2,3-tricarboxylic acid, tri (hexyl, octyl, decyl esters) is a UVCB substance manufactured from 2-Hydroxypropan-1,2,3-tricarboxylic acid and C6-10 fatty alcohols.
The target substance Reaction mass of didodecyl hydrogen citrate and tridodecyl 2-hydroxypropane-1,2,3-tricarboxylate is a multi constituent substance manufactured from 2-Hydroxypropan-1,2,3-tricarboxylic acid and 1-dodecyl alcohol.


3. ANALOGUE APPROACH JUSTIFICATION
The read-across hypothesis is based on structural similarity of the target and source substance. Based on available experimental data, including key physicochemical properties and a genotoxicity study, the read-across strategy is supported by a similar toxicological profile of the target and source substance.
The respective reliable data (RL 1 or 2) are summarized in the data matrix; robust study summaries are included in the Technical Dossier in the respective sections.
The read-across from the source substance is justified:
a) Based on the information given in section 1, it can be concluded that the substances are similar in structure, since they are manufactured from similar or identical precursors under similar conditions and all contain the same functional groups. Thus a common mode of action can be assumed.
c) The only difference within the two substances is a (minor) variation in the chain length of the alcohols used for manufacture, which is not expected to have a relevant impact on intrinsic toxic or ecotoxic activity and environmental fate.

4. DATA MATRIX
See document under "Attached justification".
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: 0.8 % aqueous hydroxypropylmethylcellulose gel (METHOCEL E 4 M, Synopharm, Barsbüttel, Germany)
Doses:
2000 / 6000 / 10000 / 20000 / 50000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 50 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality occurred
Clinical signs:
no clinical signs observed
Body weight:
normal body weight gain achieved
Gross pathology:
no test substance related findings noted

Table: Number of animals dead [and with evident toxicity] [and time range within which mortality occurred]

 

Dose
(mg/kg bw)

Mortality (# dead/total)

Time range of deaths (hours)

Number with evident toxicity(#/total)

Male

Female

Combined

Male

Female

Combined

2000

 0/5

 0/5

 0/10

 -

 0/5

 0/5

 0/10

6000

 0/5

 0/5

 0/10

 -

 0/5

 0/5

 0/10

10000

 0/5

 0/5

 0/10

 -

 0/5

 0/5

 0/10

20000

 0/5

 0/5

 0/10

 -

 0/5

 0/5

 0/10

50000

 0/5

 0/5

 0/10

 -

 0/5

 0/5

 0/10

 

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the present test condition a single oral administration of up to 50000 mg/kg b.w. to rats revealed no toxic symptoms. 50000 mg/kg equivalent to an application volume of 50 mL/kg was the highest reasonable application volume. The test substance was classified to be relatively non-toxic.
Executive summary:

The test item was investigated according to OECD Guideline 401. The test subsatnce was administered to once orally to male and female Sprague-Dawley rats by gavage a doses up to 50000 mg/kg b.w. Subsequently, observations of effects and deaths were made. All surviving animals were observed for a period of 14 days.

Under the present test condition a single oral administration of up to 50000 mg/kg b.w. to rats revealed no toxic symptoms. 50000 mg/kg equivalent to an application volume of 50 mL/kg was the highest reasonable application volume. The test substance was classified to be relatively non-toxic.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
50 000 mg/kg bw

Additional information

Justification for classification or non-classification

The acute oral toxicity was investigated according to OECD Guideline 401. Oral administration of up to 50000 mg/kg b.w. to rats revealed no toxic symptoms.

No data are available on inhalative toxicity. However, the very low vapour pressure of the substance does not indicate an inhalative hazard.

No data are available on dermal toxicity. However, taking into account the very low oral toxicity, a low dermal can be assumed as well.