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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 October 2016 - 21 March 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 2008; including the most recent amendments
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147
Version / remarks:
November 2000; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Reference substance 001
Cas Number:
210420-85-2
Constituent 2
Chemical structure
Reference substance name:
N-methyldidecylamine
EC Number:
230-990-1
EC Name:
N-methyldidecylamine
Cas Number:
7396-58-9
Molecular formula:
C21H45N
IUPAC Name:
N-decyl-N-methyldecan-1-amine
Constituent 3
Chemical structure
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
Dihydrogen oxide
impurity 1
Reference substance name:
Unknown impurities
Molecular formula:
Not available
IUPAC Name:
Unknown impurities
Test material form:
solid
Details on test material:
- Appearance: Slightly yellow gel- Storage conditions: At room temperature; container flushed with nitrogen
Specific details on test material used for the study:
Correction for purity: 1.081

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS- Source: Charles River Deutschland, Sulzfeld, Germany- Females nulliparous and non-pregnant: yes- Age at study initiation: 9-11 weeks old- Weight at study initiation: 160-199 g- Fasting period before study: yes- Housing: group housing of 3 animals per cage in labeled Makrolon cages containing sterilized sawdust as bedding material and paper as cage-enrichment. - Diet: pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum- Water: tap water, ad libitum- Acclimation period: at least 5 days ENVIRONMENTAL CONDITIONS - Temperature (°C): 18-24 - Humidity (%): 43-52 - Air changes (per hr): 10 - Photoperiod (hrs dark / hrs light): 12/12 IN-LIFE DATES: From: 10 October 2016 To: 25 October 2016

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE - Concentration in vehicle: variable to allow constant dosage volume per kg body weight. - Amount of vehicle: 10 mL - Justification for choice of vehicle: the vehicle was selected based on trial preparations performed at Charles River Den Bosch and on test item data supplied by the sponsor. MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight DOSAGE PREPARATION: Formulations were kept at room temperature and dosed within 4 hours after adding the vehicle to the test item. Homogeneity was obtained by heating the formulations in a water bath with a maximum temperature of 40.7ºC for a maximum of 63 minutes. The formulations were allowed to cool to a temperature of maximally 40ºC prior to dosing. CLASS METHOD - Rationale for the selection of the starting dose: the starting dose was according to OECD guideline 423 (2000 mg/kg body weight). However, because no correction for the water content and impurities was made at dosing of the intended dose of 2000 mg/kg, the actual dose applied was 1850 mg/kg. The presence of mortality determined the dosing in the next step (300 mg/kg body weight).
Doses:
The study was performed in a stepwise manner with a starting dose of 1850 mg/kg. The presence of mortality determined the dose of 300 mg/kg for the next steps.
No. of animals per sex per dose:
3 females per test (9 in total)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days - Frequency of weighing: on days 1, 8 and 15 and at death- Frequency of observations: Mortality/viability: twice daily Clinical signs: at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 1 850 mg/kg bw
Based on:
test mat.
Mortality:
At 1850 mg/kg, one animal was found dead on day 2 and two animals were euthanized moribund on day 2.At 300 mg/kg, one animal was found dead on day 14 and one animal was euthanized moribund on day 9. The remaining four animals survived until the end of the observation period.
Clinical signs:
At 1850 mg/kg, hunched posture, uncoordinated movements and piloerection were noted for all animals on days 1 and 2 and lethargy, flat posture, laboured respiration, shallow respiration, diarrhoea, salivation, pale appearance and ptosis were noted for all animals onday 2.At 300 mg/kg, hunched posture, piloerection, salivation, distended abdomen (with gas) and/or ptosis were noted for all animals between days 1 and 15. Additionally, for the animal found dead, diarrhoea and gasping were noted on day 6 and rales were noted between days 7 and 14.
Body weight:
The mean body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
At 1850 mg/kg, many abnormalities of the stomach gastrointestinal tract and liver were found at post mortem examination.At 300 mg/kg, many abnormalities of the stomach, spleen, thymus and liver were found and growing together of organs in the abdominal cavity was found at post mortem examination. Cannibalism was noted for the animal found dead (300 mg/kg).

Any other information on results incl. tables

Results of chemical analysis of dose formulations:

Chemical analysis showed that the test item formulations can be considered stable as used under the conditions during the study.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Category 4 according to Regulation (EC) No 1272/2008
Conclusions:
In an acute oral toxicity study with rats, performed according to OECD guideline 423 and GLP principles, the oral LD50 of 1-Decanaminium, N-decyl-N,N-dimethyl-, heaxanedioate (2:1) was established to be within the range of 300-1850 mg/kg body weight. Based on these results, the test substance is classified as Category 4 according to GHS and as Category 4 (labeled as H302) according to Regulation (EC) No 1272/2008.

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