Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03 July 2015 - 04 August 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous
Details on test material:
- Name of test material (as cited in study report): di-C16-C18 (evennumbered) alkyl tripropylenetetramine
- Substance type: Viscous liquid
- Physical state: Liquid
- Storage condition of test material: At room temperature container flushed with nitrogen
- Batch/Lot number: B1; batch inspection lot no.:890000394200
- Expiration date of the lot/batch: 22 October 2017
- Purity: 100% (UVCB substance)
- pH: 8.5-10.5 (1% solution)
- specific gravity: 0.83 at 60°C

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8-9 weeks old)
- Weight at study initiation: 155-164 g (1st group); 159-172 g (2nd group); 153-156 g (3rd group)
- Fasting period before study: Animals were deprived of food overnight prior to dosing
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): set to maintain 18 – 24
- Humidity (%): set to maintain 40 - 70
- Air changes (per hr): set to maintain at least 10
- Photoperiod (hrs dark / hrs light): set to maintain 12/12
Temporary deviations from the maximum and minimum level of daily mean relative humidity occurred. As laboratory historical data do not indicate an effect of the deviations, the study integrity was not adversely affected.

IN-LIFE DATES: From: 03 July 2015 to 04 August 2015

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Remarks:
(Fagron Capelle a/d IJssel, The Netherlands) (specific gravity 0.92)
Details on oral exposure:
GAVAGE METHOD: plastic feeding tubes

Frequency: single dosage, on Day 1

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial preparations performed at WIL Research Europe

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION
- The preparations (w/w) were kept at room temperature and were dosed within 4 hours after adding the vehicle to the test substance
- Homogeneity was assessed by visual inspection of the solutions and the formulations were stirred during dosing, which ensures homogeneity sufficient for these kinds of studies
- Adjustment was made for specific gravity of the vehicle
- The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of mL/kg body weight

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on anticipated mortality at the next higher dose
Doses:
- 300 mg/kg bw
- 2000 mg/kg bw
No. of animals per sex per dose:
- 300 mg/kg bw: 3
- 2000 mg/kg bw: 6 (2 groups of three females)
Control animals:
no
Details on study design:
- The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 300 mg/kg bw. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.
- Animals were deprived of food until 3-4 hours after administration of the test substance
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
No mortality occurred.
Clinical signs:
- At 300 mg/kg bw, the animals showed no clinical signs
- At 2000 mg/kg bw, hunched posture and/or piloerection were noted for the animals between Days 1 and 3
Body weight:
The body weight gain shown by the 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:
No test substance related abnormalities were found.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study with di-C16-C18 (evennumbered) alkyl tripropylenetetramine in rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.
Executive summary:

The acute oral toxicity of di-C16-C18 (evennumbered) alkyl tripropylenetetramine was determined in accordance with OECD 423 (2001) and according to GLP principles. Initially, the substance was administered by oral gavage to a group of three female Wistar rats at 300 mg/kg bw. In a stepwise procedure two additional groups of three females were dosed at 2000 mg/kg bw. No mortality occurred. At 300 mg/kg bw, the animals showed no clinical signs. At 2000 mg/kg bw, hunched posture and/or piloerection were noted for the animals between Days 1 and 3. Body weight gain and necropsy did not show any abnormality. The acute oral toxicity (LD50) was determined to be >2000 mg/kg bw. Based on this result, di-C16-C18 (evennumbered) alkyl tripropylenetetramine does not need to be classified for acute toxicity by the oral route according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg bw.