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Administrative data

Description of key information

Two recent GLP studies that were performed according to OECD guidelines are present for acute toxicity oral and acute toxicity dermal (Salvador, 2014 and 2014a). Both studies did not show any adverse effects up to a concentration of 2000 mg/kg bw.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Recent GLP study according to international guidelines.
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
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy s.r.l, San Pietro al Natisone (UD) Italy
- Age at study initiation: 7 weeks old
- Weight at study initiation: 157-163 grams
- Fasting period before study: food was removed from the cage overnight prior to dosing
- Housing:Polisulphone solid bottomed cage measuring 59,5x38x20 cm with nesting material provided into suitable bedding bags
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +- 2°C
- Humidity (%): 55% +- 15%
- Air changes (per hr): 15 to 20/ hour
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200mg/mL
MAXIMUM DOSE VOLUME APPLIED: 10mL/kg
Doses:
2000mg/kg
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 2x/day
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality occured
Clinical signs:
no clinical signs were observed in the 2 groups of animals initially dosed at 2000mg/kg
Body weight:
body weight observed during the study were within the expected range for this strain and age of animals
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute toxicity for Trimethylolpropane Tripelargonate is expected to be greater than 2000 mg/kg body weight.
Executive summary:

The acute toxicity of Trimethylolpropane Tripelargonate was investigated following a single oral administration to the Sprague Dawley rat followed by a 14-day observation period. A first group of 3 female animals was initially dosed at 2000 mg/kg (Step 1). No mortality occurred and no clinical signs were observed. A second group of 3 female animals was then dosed at the same dose level (Step 2). No death occurred and no clinical signs were noted. Body weight changes recorded during the study were within the expected range for this strain and age of animals. No abnormalities were observed at necropsy examination performed at the end of the observation period on animals of both groups. These results indicate that the test item Trimethylolpropane Tripelargonate did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg body weight. European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC) No. 1272/2008 and subsequent revisions) would indicate the following:

- Classification: not required

- Signal word: not required

- Labeling: not required

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Recent OECD guideline study following GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Species and strain:
Rat, Hsd: Sprague Dawley SD

Sex:
Males and females (nulliparous and non-pregnant)

Age:
6 to 8 weeks old

Weight at order:
176 to 200 grams

Supplier:
Harlan Italy s.r.l., San Pietro al Natisone (UD), Italy

Weight range at arrival:
171 to 181 grams

Acclimatisation period:
At least 5 days

Animals per cage:
Up to 5 of one sex to a cage

Housing:
Clear polysulphone H-Temp solid bottomed cages (Techniplast Gazzada S.a.r.l., Buguggiate, VA, Italy) measuring 59.53820 cm during acclimatisation
period and 42.526.618.5 cm during the study with stainless steel mesh lid and floor.

Cage control:
Daily inspected and changed as necessary (at least 3 times/week)

Water:
Drinking water supplied to each cage via a water bottle

Water supply:
Ad libitum

Diet:
4 RF 18 (Mucedola S.r.l., Via G. Galilei, 4, 20019, Settimo Milanese (MI) Italy)

Diet supply:
Ad libitum throughout the study

Room lighting:
Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

Air changes:
Approximately 15 to 20 air changes per hour

Temperature range:
22 ± 2 °C

Relative humidity range:
55 ± 15%
Type of coverage:
semiocclusive
Details on dermal exposure:
Selection/Allocation:
Random at arrival. The body weight of each individual was within 20% of the mean and within the range of 200-300 grams. Animals were unequivocally numbered within the study. The animal number together with the study number ensured a unique animal numbering for any study employing computerised data collection.

Animal identification:
Animals were permanently identified, following arrival, by a combination of ear notch (units) and tattoo on the hind feet. Males and females were
identified by even and odd numbers, respectively.

Frequency of treatment:
Animals were dosed once only on Day 1.

Treatment area preparation:
On the day before dosing (Day –1), a single area was clipped free of hair (by an electric clipper equipped with a suitable blade) on the dorsal surfaces of the trunk of each animal (approximately 10% of body surface). Care was taken to avoid damage to the skin.

Dose calculation:
On the day of dosing (Day 1), the aliquots were weighed according to the body weight of each animal measured prior to dosing.

Dosing procedure:
An aliquot of the supplied test item was spread evenly over an area of approximately 10% of the body surface area. A patch of surgical gauze
covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a
length of elastic adhesive bandage, this forming a semi-occlusive barrier.

Washing procedure
After exposure, the adhesive bandage and gauze patch were removed. The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with lukewarm water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
A single group of 5 male and 5 female animals was dosed at a level of 2000 mg/kg.
Control animals:
not required
Details on study design:
In vivo observations

Mortality and morbidity:
Throughout the study all animals were checked twice daily.

Clinical signs:
Animals were observed for clinical signs as indicated below (and daily after a total of 14 days)

Day of dosing
– Session 1: on dosing
– Session 2: approximately 1 hour after dosing
– Session 3: 2 hours after dosing
– Session 4: 4 hours after dosing

Body weight
All animals were weighed at allocation to the study (Day -1), on the day of dosing (Day 1) and on Days 8 and 15. Body weight change calculated for Days 8 and 15 of the dosing phase was relevant to Day 1 of the phase.

Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
These results indicate that the test item, Trimethylolpropane Tripelargonate, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg.The dermal LD50 of Trimethylolpropane Tripelargonate was determined to be > 2000 mg/kg.
Executive summary:

The acute toxicity of Trimethylolpropane Tripelargonate was investigated following dermal administration of a single dose to the rat. A single dose of 2000 mg/kg was administered to a group of 5 male and 5 female animals for 24 hours. After 14 days, all animals were killed and subjected to necropsy examination. No mortality occurred and no signs of toxicity were observed in male or female animals during the observation period. The body weight changes observed during the study were within the expected range for this species and age of animals. No abnormalities were found at necropsy in the animals at termination of the study, nor at the treated site. These results indicate that the test item, Trimethylolpropane Tripelargonate, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
There is only one study available but this study is a well documented, and performed recent GLP study according to international guidelines.

Justification for selection of acute toxicity – inhalation endpoint
Data on toxicity via the oral and dermal route is available. Futhermore, the substance is a viscous oil and the inhalation route of exposure is not considered to be the most relevant one.

Justification for selection of acute toxicity – dermal endpoint
There is only one study available but this study is a well documented, and performed recent GLP study according to international guidelines.

Justification for classification or non-classification

Based on the acute toxicity results, showing LD50 values > 2000 mg/kg bw for oral and dermal administration,the substance should not be classified as acute toxic according to the criteria described in EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP) or Directive 67/548/EEC (Dangerous Substances Directive).