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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-07-16 to 2012-11-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
(Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, München, Germany)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Fatty acids, C16-18, reaction products with diethanolamine
EC Number:
293-014-3
EC Name:
Fatty acids, C16-18, reaction products with diethanolamine
Cas Number:
91032-08-5
Molecular formula:
C22H45NO3 to C52H101NO5
IUPAC Name:
Fatty acids, C16-18, reaction products with diethanolamine
Details on test material:
Name: Fatty acids, C16-18-, reaction products with diethanolamine
Product: Cepreton AT liq. conc.
Specification: Amide Intermediate of Cepreton AT (REACH)
CAS No.: 91032-08-5
Batch No.: ITA0058330
Physical State: solid
Colour: yellow
Molecular Weight: ca. 610-872
pH: 7-8
Active Components: > 99%
Storage Conditions: at room temperature, protected from light
Date of Analysis: 01.02.2012
Expiry Date: 11.01.2013
Safety Precautions: The routine hygienic procedures were sufficient to assure personnel health and safety.

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
Housing and Feeding Conditions
- Full barrier in an air-conditioned room
- Temperature: 22 +/- 3 °C
- Relative humidity: 55 +/- 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: 10 x / hour
- Free access to Altromin 1324 maintenance diet for rats and mice
- 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)
- The animals were kept in groups / individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Adequate acclimatisation period (at least five days) under laboratory conditions

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The animals were marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.
The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 10 mL/kg body weight.
Doses:
Dose Level:
The starting dose was selected to be 2000 mg/kg body weight. No compound-related mortality was recorded for any animal of step 1 or 2. Based on these results and according to the acute toxic class method regime no further testing was required.
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:

All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15. 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). As soon as symptoms were noticed they were recorded. 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. At the end of the observation period the surviving animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally (Narcoren®, Merial; lot no.: 221022; expiry date: 02/2015) at a dosage of approximately 8 mL/kg bw. All animals were subjected to gross necropsy. All gross pathological changes were recorded.
Statistics:
According to OECD guidelines, the biological relevance of the results is the criterion for the interpretation of results, a statistical evaluation of the results is not regarded as necessary.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
All animals survived until the end of the study without showing any signs of toxicity.
Clinical signs:
None.
Body weight:
Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain.
Gross pathology:
At necropsy, no macroscopic findings were observed in any animal of any step.

Any other information on results incl. tables

Table: Clinical Signs - Individual Data


 















































Animal
No. / Sex



Time of
Observation
Post-Dose



Observations



Step 1 (2000 mg/kg Body Weight)



1 / female



during the whole observation period



no signs of toxicity



2 / female



during the whole observation period



no signs of toxicity



3 / female



during the whole observation period



no signs of toxicity



Step 2 (2000 mg/kg Body Weight)



4 / female



during the whole observation period



no signs of toxicity



5 / female



during the whole observation period



no signs of toxicity



6 / female



during the whole observation period



no signs of toxicity



 


Table: Body Weight Development - Absolute Body Weights in g and Body Weight Gain in %


 





























































Animal No. /
Sex



g
Day 1



g
Day 8



g
Day 15



%
Day 1-15



Step 1 (2000 mg/kg Body Weight)



1 / female



166



191



197



19



2 / female



183



204



226



23



3 / female



170



195



206



21



Step 2 (2000 mg/kg Body Weight)



4 / female



171



192



200



17



5 / female



159



177



185



16



6 / female



162



185



197



22



 


Table: Findings of Necropsy - Individual Data


 















































Animal No./
Sex



Organ



Macroscopic Findings



Step 1 (2000 mg/kg Body Weight)



1 / female



-



nsf



2 / female



-



nsf



3 / female



-



nsf



Step 2 (2000 mg/kg Body Weight)



4 / female



-



nsf



5 / female



-



nsf



6 /female



-



nsf



nsf = no specific findings


 


Table: LD50 Cut-Off


 


















Dose
(unit)



Number of
Animals
Investigated



Number of Intercurrent Deaths



LD50 Cut-Off



2000 mg/kg bw



6



0



unclassified



bw = body weight

Applicant's summary and conclusion

Conclusions:
Under the conditions of the present study, a single oral application of the test item Fatty acids, C16-18-, reaction products with diethanolamine to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.
The median lethal dose of Fatty acids, C16-18-, reaction products with diethanolamine after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): unclassified
Executive summary:

1.1.           Summary Results


Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was suspended in the vehicle aqua ad injectionem (sterile water) at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.


All animals used in the study after their entrance at BSL were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15.All animals were necropsied and examined macroscopically.


Table: Results per Step



























Step



Sex/No.



Dose (mg/kg)



Number of Animals



Number of Intercurrent Deaths



1



female/1-3



2000



3



0



2



female/4-6



2000



3



0



All animals survived until the end of the study without showing any signs of toxicity.


Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain.


At necropsy, no macroscopic findings were observed in any animal of any step.


LD50cut-off:                                                     unclassified


Species/strain:                                                   WISTAR Crl: WI(Han) rats


Number of animals:                                           3 per step / 2 steps performed


Vehicle:                                                            aqua ad injectionem


Method:                                                             OECD 423
          EC 440/2008, Method B.1 tris
          OPPTS 870.1000
          OPPTS 870.1100


 


 


Conclusion


Under the conditions of the present study, a single oral application of the test item Fatty acids, C16-18-, reaction products with diethanolamine to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.


The median lethal dose of Fatty acids, C16-18-, reaction products with diethanolamine after a single oral administration to female rats, observed over a period of 14 days is:


LD50cut-off (rat): unclassified