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Diss Factsheets

Administrative data

Description of key information

Acute toxicity: Oral LD50 between 300 and 2000 mg/kg for rat (LD50 cut-off: 1000 mg/kg bw)No data is available on acute toxicity via inhalation or dermal route.

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:
5-30 June 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
reference to other study
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
Qualifier:
according to guideline
Guideline:
other: other guideline: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no
Specific details on test material used for the study:
Substance as described in Chapter 1.1
Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: approx. 9-11 weeks old
- Weight at study initiation: 173-204 grams. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: yes, overnight prior to dosing and until 3-4 hours after administration of the test substance
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material and paper as cage-enrichment.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period:at least 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4 – 21.0ºC
- Humidity (%): 40 - 79%
- Air changes (per hr): approx.15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 05 June 2009 To: 30 June 2009
Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 mg/kg: 30 mg/mL, and 2000 mg/kg: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor


MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg


DOSAGE PREPARATION (if unusual):
The formulations (w/w) were prepared within 4 hours prior to dosing, and were flushed with nitrogen. Homogeneity was accomplished to a visually acceptable level. In order to obtain homogeneity, the test substance formulations were heated in a water bath with a maximum temperature of 50ºC for a maximum of 11 minutes. The test substance (formulations) were allowed to cool down to a temperature of maximally 40ºC prior to dosing. Adjustment was made for specific gravity of the vehicle and for density of the test substance. 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 toxicity at 2000 mg/kg.
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
300 mg/kg: two groups of 3 females
2000 mg/kg: one group of 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. Weighing: Days 1 (pre-administration), 8 and 15 and at death (if found dead after Day 1).
- Necropsy of survivors performed: yes
- Other examinations performed: none.
Statistics:
Not applicable.
Preliminary study:
Not applicable.
Sex:
female
Dose descriptor:
LD50
Effect level:
>= 300 - <= 2 000 mg/kg bw
Mortality:
The incidence of mortality was as follows, presented in chronological order of treatment:
Dose level Mortality Date of treatment
300 mg/kg 0/3 05 June 2009
300 mg/kg 0/3 09 June 2009
2000 mg/kg 2/3 16 June 2009

The decedents were found on day 2 post-treatment.
Clinical signs:
other: Hunched posture, rales, salivation and/or piloerection were observed among all females at 300 mg/kg. Hunched posture, uncoordinated movements and piloerection were noted among all females at 2000 mg/kg. The surviving animals had recovered from the sympto
Gross pathology:
A beginning stage of autolysis was noted among the animals found dead at 2000 mg/kg.

No macroscopic abnormalities were noted among animals at 300 mg/kg, and in the surviving female at 2000 mg/kg.
Other findings:
None.

None.

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The oral LD50 value of Oleyl tripropylenetetramine in Wistar rats was established to be within the range of 300-2000 mg/kg body weight, with LD50 cut -off: 1000 mg/kg.
Executive summary:

The incidence of mortality was as follows, presented in chronological order of treatment:

Dose level                    Mortality                       Date of treatment

300 mg/kg                    0/3                               05 June 2009

300 mg/kg                    0/3                               09 June 2009

2000 mg/kg                  2/3                               16 June 2009

The decedents were found on day 2 post-treatment.

Hunched posture, rales, salivation and/or piloerection were observed among all females at 300 mg/kg. Hunched posture, uncoordinated movements and piloerection were noted among all females at 2000 mg/kg.

The surviving animals had recovered from the symptoms between Days 3 and 5, except for animal no. 1 (300 mg/kg) showing rales up to scheduled necropsy.

Animals found dead at 2000 mg/kg showed slight body weight loss. The surviving female at 2000 mg/kg showed a slightly reduced body weight gain between days 1 and 8.

The body weight gain shown by the animals at 300 mg/kg over the study period was considered to be normal.

A beginning stage of autolysis was noted among the animals found dead at 2000 mg/kg.

No macroscopic abnormalities were noted among animals at 300 mg/kg, and in the surviving female at 2000 mg/kg.

The oral LD50value of Oleyl tripropylenetetramine in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 1000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 000 mg/kg bw
Quality of whole database:
Guideline studies (OECD 423) under GLP. All data show consistent results over the group of polyamines.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Scientific and exposure related waiving: Corrosive and low likelihood for exposure via inhalation.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Scientific and exposure related waiving: Corrosive and low likelihood for exposure.

Additional information

Acute oral toxicity:

Three groups of Wistar rats, each comprising 3 females, received a single oral dose at 300, 300 and 2000 mg/kg body weight of Oleyl tripropylenetetramine respectively. The incidence of mortalities was 0/3, 0/3 and 2/3 respectively. Deaths occurred within 1 day of dosing.

Hunched posture, rales, salivation and/or piloerection were observed among all females at 300 mg/kg. Hunched posture, uncoordinated movements and piloerection were noted among all females at 2000 mg/kg. The surviving animals had recovered from the symptoms between Days 3 and 5, except for one animal at 300 mg/kg showing rales up to scheduled necropsy.

The animals found dead at 2000 mg/kg showed slight body weight loss. The surviving female at 2000 mg/kg showed a slightly reduced body weight gain between days 1 and 8. The body weight gain shown by the animals at 300 mg/kg over the study period was considered to be normal.

A beginning stage of autolysis was noted among the animals found dead at 2000 mg/kg.

No macroscopic abnormalities were noted among animals at 300 mg/kg, and in the surviving female at 2000 mg/kg.

The oral LD50value of Oleyl tripropylenetetramine in Wistar rats was established to be within the range of 300-2000 mg/kg body weight, and the LD50 cut-off value was considered to be 1000 mg/kg body weight.

 

Comparable other triamines (alkyl dipropylenetriamine) and tetramines (alkyl tripropylenetatraamine) show similar results, where those with on average shorter alkyl chains show a somewhat higher toxicity compared to those with longer alkyl chain lengths:

Acute toxicity Triamines:

           Coco   50-300 mg Cat.3; cut off 200

           Tallow  300-2000 mg Cat.4; cut-off 500

           Oleyl    300-2000 mg Cat.4; cut-off 500

Acute toxicity Tetraamines:

           Tallow  300-2000 mg Cat.4; cut-off 500

           Oleyl    300-2000 mg Cat.4; cut-off 1000

 

In conclusion, there is little effect of the actual number propylene amine groups between linear triamine and linear tetraamine. With increasing length of the alkyl chain, the acute toxicity decreases.

 

Acute dermal toxicity:

Polyamines are corrosive to the skin. Testing for acute dermal toxicity is therefore not justified. Toxicity following dermal exposure is characterised by local tissue damage, rather than the result of percutaneously absorbed material.

Dermal absorption of cationic surfactants can be expected to be low. The stratum corneum consists of many membrane layers in which these surface active cationics are easily bound.

The situation can be compared to the situation for hydrocarbons, where those ≥ C14 are only poorly absorbed through the skin and do not penetrate beyond the stratum corneum. Whereas the hydrocarbon can freely move through the lipid layers, the surfactants have besides a large apolar tail in the lipid layer, a polar, cationic charged head sticking out, which basically keeps them trapped in the lamellar lipid layers of the corneum. In case of excess substance, it will be distributed evenly throughout the whole stratum corneum. However, the fraction adsorbed is rather fixed in the membrane structure and the substance bound in the stratum corneum is not mobile.

 

Acute inhalation toxicity:

Physical-chemical properties of Oleyl tripropylenetetramine indicate a low likelihood for exposure via inhalation. The paste has a boiling point > 300 °C and a low vapour pressure (4.7 x 10-5 Pa at 20°C for the coco dipropylene triamine, with the shortest average alkyl chain length representing the highest vapour pressure for the group of tri- and tetramines). Its use is limited to industrial and professional users and does not involve the forming of aerosols, particles or droplets of an inhalable size. So exposure to humans via the inhalation route will be unlikely to occur. Furthermore, as the substance is classified as corrosive, such testing should normally not be conducted.

Justification for classification or non-classification

Acute oral exposure of Oleyl tripropylenetetramine leads to harmful effects, with a LD50 between 300 and 2000 mg/kg bw, with an LD50 cut-off level of 1000 mg/kg bw. The substance therefore need to classified as “ Cat.4 harmful if swallowed” for acute oral toxicity for GHS.

 

Acute dermal testing with these very corrosive materials is not justified. As a consequence no classification can be made for acute dermal toxicity. Effects will be characterised by local tissue damage. Systemic uptake via skin is likely to be very limited.

 

Also for acute inhalation toxicity information for classification is lacking, and is testing not justified. The likelihood of exposure via inhalation is low.

 

No classification STOT-SE Cat.3 needed:

Polyamines are not structurally related to any known class of neurotoxic chemicals. In addition, repeated dose studies did not show indications of specific neurotoxicity, in specific neurotoxicity measures as sensory activity, grip strength, and motor activity assessment.

 

Polyamines do not contain containing aliphatic, alicyclic and aromatic hydrocarbons and so do not indicate an immediate concern for aspiration hazard. Besides, Oleyl tripropylenetetramine is a solid.