Registration Dossier

Administrative data

Description of key information

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:
19.01.2015 - 19.02.2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed according to international accepted testing guideline, well documented
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 10-12 weeks
- Weight at study initiation: female: 155 - 171 g
- Fasting period before study: 16 - 19 h (access to water was permitted)
- Housing: in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 02102140831)
- Diet: ad libitum, Altromin 1324 maintenance diet for rats and mice (lot no. 1239)
- Water: ad libitum, tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least 5 days
The animals were non-pregnant and nulliparous.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10x
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/ml
- Amount of vehicle (if gavage):10 mL/kg bw
- Justification for choice of vehicle: The vehicle was chosen due to its non-toxic characterics
- Lot/batch no. (if required): Sigma, lot no. MKBQ546V, expiry date: 31 March 2015
- Purity: not mentioned

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION: 2 g of the test item were suspended in 10 mL of the vehicle. Test item in the vehicle was maintained by vortexing the prepared suspension thoroughly before each dose administration.

CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose was selected to be 2000 mg/kg bw, no toxicity was expected.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6 (3 in each of 2 steps)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful clinical examination was made several times on the day of dosing (at least once) during the first 30 minutes and with special attention given during the first 4 hours post-dose. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded. Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The animals were weighed on day 1 prior to the administration and on days 8 and 15.
- Necropsy of survivors performed: yes, at the end of the observation period the animals were sacrified by an over-dosage of phenobarbital injected intraperitoneally.
Statistics:
not performed
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred throughout the study.
Clinical signs:
No specific findings.
Body weight:
None of the animals showed weight loss during the observation period.
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.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No animal died. In the study performed the dosis letalis media (LD50) to rats was found to be > 2000 mg/kg bodyweight.
Executive summary:

Under the conditions of the present study, a single oral application of the test item 2 -decyltetradecanoic acid to rats at a dose 2000 mg/kg body weight was associated with no signs of toxicity or mortality. The median lethal dose of 2 -decyltetradecanoic acid after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): >5000 mg/ kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Klimish 1

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:
04.02.2015 - 18.02.2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
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: males: 09 -10 weeks old; females: 12 -13 weeks old
- Weight at study initiation:237 - 244 g (males); 217 - 227 g (females)
- Housing: The animals were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 1239)
- Diet (e.g. ad libitum): Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 02102140831)
- Water (e.g. ad libitum): Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 ° C
- Humidity (%): 45 -65
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: 2015-01-29 To: 2015-02-18
Type of coverage:
semiocclusive
Vehicle:
other: Aqua ad injectionem (AlleMan Pharma, lot no. 260813_1, expiry date: 31 July 2016)
Details on dermal exposure:
TEST SITE
- Area of exposure: uniformly over an area
- % coverage: 10
- Type of wrap if used: The test item was held in contact with the skin by a dressing throughout a 24-hour period. The dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, at the end of the exposure period the residual test item was removed using aqua ad injectionem
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: in order to ensure good skin contact, the test item was moistened with the vehicle.

VEHICLE
- Lot/batch no. (if required): 260813_1,
Duration of exposure:
24 hours
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: Observations for mortality and clinical/behavioral signs of toxicity were made at least three times on the day of dosing (day 0) and at least once daily thereafter.
- Necropsy of survivors performed: yes, at the end of the observation period the all animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally (Narcoren® Merial; lot no.: 236014; expiry date: 31 January 2016) at a dosage of 250-400 mg/kg bw.
- Other examinations performed: Individual body weights were recorded just prior to dosing and on days 1; 8 and 15. Observations for evidence of dermal irritation were made all days.

Individual reactions of each animal were recorded at each time of observation.
Toxic response data were recorded by sex and dose level.
Nature, severity and duration of clinical observations were described.
The body weight changes were summarised in a tabular form.
Necropsy findings were described.
With few exceptions, data were captured using the validated departmental computerized system E-WorkBook (version 9.4.0, ID Business Solutions Ltd.).
Statistics:
not performed
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no mortality occurred
Clinical signs:
The test item showed no signs of acute dermal toxicity and no signs of dermal irritation after a single dose application.
Body weight:
No specific findings
A slight weight loss was recorded for 1 out of 5 female animals during the first week, but all of the female animals showed weight gain during the second week. The effects on weight development might be secondary to the dressing, and toxicological relevance of this finding cannot clearly be concluded.
The male animals showed weight gain during the first and the second week of the observation.
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
Other findings:
none
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 was greater than 2000 mg/kg bodyweight in male and female rats.
Executive summary:

Under the conditions of the present study, single dermal application of the test item 2 -decyltetradecanoic acid to rats at a dose of 2000 mg/kg body weight was associated with no mortality and neither signs of toxicity nor signs of irritation. The dermal LD50 was determined to be > 2000 mg 2 -decyltetradecanoic acid / kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
Klimish 1

Additional information

Justification for classification or non-classification

All acute studies (oral, dermal) showed that the target substance is practically not toxic with LD50 > 2000 mg/kg. Therefore the substance is not classified.