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Description of key information

The test substance was tested in an acute oral fixed dose test in rats. No mortality was observed at 2000 mg/kg bw. The LD50 is >2000 mg/kg bw. An analogue of the test substance was tested in an acute dermal toxicity study in rats. The LD50 is >2000 mg/kg bw. No inhalation study is available as exposure via the inhalation route is expected to be negligible.

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:
21-08-2012 to 12-09-2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study under GLP
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 156-174 g
- Fasting period before study: 24 hours before dosing and 3-4 hours thereafter
- Housing: 4/cage in solid-floor polypropylene cages furnished with woodflakes
- Diet: 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK ad libitum
- Water: ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25°C
- Humidity (%): 30-70%
- Air changes (per hr): >15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
DMSO
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
DOSE VOLUME APPLIED: 10 mL

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
1 female in the pre-test (2000 mg/kg bw), 4 females in the main study
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality twice daily; body weight on day 0 (before treatment), day 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs ½, 1, 2, and 4 hours after dosing and daily thereafter
Statistics:
NA, limit test
Preliminary study:
No mortality at 2000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
Hunched posture and lethargy in one animal on day 0
Body weight:
within normal ranges
Gross pathology:
no effects
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 after oral application of the test substance is > 2000 mg/kg bw
Executive summary:

Female rats (n=5) received a single oral dose of 2000 mg/kg bw of the test substance. No effects on clinical signs, body weight and macroscopic examinations. No mortality was observed. The LD50 is > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
A study with a analogue (Stillmeadow, 2001) is available, that shows and LD50 after oral application of >2020 mg/kg bw. This value is as expected similar to the value found in the key study with the test substance.

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:
March 23 - April 7, 2010
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (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: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: females: 8-9 weeks, males: 8-9 weeks old
- Weight at study initiation: females: 216-225 g, males 237-254 g
- Housing: The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): Free access to Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): Free access to tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological control at regular intervals)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark

Type of coverage:
semiocclusive
Vehicle:
cotton seed oil
Duration of exposure:
The test item was held in contact with the skin throughout a 24-hour period.
Doses:
The test item was applied at a single dose of 2000 mg/kg body weight to each animal.
No. of animals per sex per dose:
Number of animals: 5 male and 5 female.
Control animals:
yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was seen.
Clinical signs:
No treatment related effects were observed.
Body weight:
The body weight development of all male and female animals was within the expected range, except for 1 out of 5 female animals
Gross pathology:
With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal

Erythema grade 1 was observed in 3 out of 5 female animals and 2 out of 5 male animals. Desquamations were observed in all the animals. Eschar was observed in 1 out of 5 female and 3 out of 5 male animals. Scratches were observed in 3 out of 5 male animals. All signs of irritation were reversible within the observation period.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 was determined to be > 2000 mg Fatty acids, tall-oil, reaction products with diethylenetriamine, maleic anhydride, tetraethylenepentamine and triethylenetetramine /kg body weight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Study with analogue recently performed according to the guidelines and under GLP

Additional information

Female rats (n=5) received a single oral dose of 2000 mg/kg bw of the test substance. No effects on clinical signs, body weight and macroscopic examinations. No mortality was observed. The LD50 is > 2000 mg/kg bw (Harlan 2012g).

The analogue substance was evaluated for its acute oral toxicity potential when administered to albino rats. The acute oral LD50, as indicated by the data, is greater than 2020 mg/kg in males and females (Stillmeadow 2001).

The dermal LD50 was determined to be > 2000 mg /kg body weight for the stuctural analogue (BSL 2001a).

The rationale for read-across is documented under chapter 13. Based on the similarity and the similar outcome of the results of the bridging studies (phys-chem, ecotoxicity and toxicity studies), the read-across is considered valid and the data on the analogue can be used for the test substance.

Justification for selection of acute toxicity – oral endpoint
Study according to the guideline and GLP

Justification for selection of acute toxicity – inhalation endpoint
In view of the low vapour pressure (1.9E-03 Pa at 25 °C) and the extreme viscosity of the test substance, exposure via the inhalation route is expected to negligible.

Justification for selection of acute toxicity – dermal endpoint
Study with analoguous compound as indicated in the document on read-across in chapter 13. As the outcome of the bridging studies (acute oral toxicity, sensitization) provide similar results, it is concluded that this study is sufficient to adequately assess the acute dermal toxicity of the test compound, that is expected to be in a similar range. Local irritant effects were reported to be fully reversible.

Justification for classification or non-classification

The test substance does not need to be classified for acute toxicity.