N-[3-(isodecyloxy)propyl]propane-1,3-diamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study according GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(isodecyloxy)propyl]propane-1,3-diamine

EC Number:

276-432-0

EC Name:

N-[3-(isodecyloxy)propyl]propane-1,3-diamine

Cas Number:

72162-46-0

Molecular formula:

C16H36N2O

IUPAC Name:

(3-aminopropyl)({3-[(2-methylnonyl)oxy]propyl})amine

Test material form:

other: liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Italy
- Age at study initiation: 6 - 7 weeks
- Weight at study initiation: 150 - 174 g
- Fasting period before study: overnight
- Housing: solid bottomed cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 2°C
- Humidity (%): 55% +/- 15%
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12 hours periodically

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% aqueous solution of carboxymethylcellulose

Doses:

300 mg/kg body weight, 50 mg/kg body weight

No. of animals per sex per dose:

6 female animals (300 mg/kg group)
6 female animals (50 mg/kg group)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality / morbidity twice daily, clinical signs daily, body weights on day 1, 2, 8 and 15
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 50 - < 300 mg/kg bw

Based on:

test mat.

Mortality:

mortality rate at 300 mg/kg body weight: 4 out of 6 females [1 of 3 female animal from subgoup 1 (300 mg/kg body weight) plus 3 of 3 female animals from subgroup 2 (300 mg/kg body weight)];
mortality rate at 50 mg/kg body weight: 0 out of 6 females

Clinical signs:

other: 300 mg/kg body weight: hunched posture, piloerection, reduced activity 50 mg/kg body weight: salivation, rales, reduced activity, piloerection

Gross pathology:

No abnormalities at necropsy (neither at 300 mg/kg body weight nor at 50 mg/kg body weight)

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category III

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median letal dose (LD50) after oral administration of the registration substance to rats is between 50 mg/kg body weight (0% mortality) and 300 mg/kg body weight (67% mortality). Based hereupon the registration substance is considered to be toxic if swallowed (category 3 according to GHS-CLP).

Executive summary:

The acute toxicity of the registration substance was investigated following a single oral administration to the Sprague Dawley rat followed by a 14-day observation period. The study was performed according to OECD TG 423 (acute toxic class method) and followed the principles of GLP. Two doses in 4 different testong steps (subgroups) had been investigated.

 

300 mg/kg (Steps 1 and 2)

A sub-group of 3 female animals was initially dosed at 300 mg/kg (Step 1). One animal was found dead on Day 8 of the study. Hunched posture, piloerection, thin appearance, reduced activity, brown staining on the muzzle and semi-closed eyes were observed before death. No mortality nor significant clinical signs were observed in the remaining two animals. A second sub-group of 3 female animals was then dosed at the same dose level (Step 2). All animals were found dead between Day 2 and 3 of the study. The following signs were noted before death: salivation, piloerection, hunched posture, soft faeces, reduced activity and semi-closed eyes. No abnormalities were observed at necropsy examination performed on all animals at the end of the observation period, including the early decedent animals.

50 mg/kg (Steps 3 and 4)

A third sub-group of 3 females was dosed at 50 mg/kg (Step 3). No deaths occurred and clinical signs observed on the day of dosing were limited to salivation and rales. Two out of three animals recovered by 2 hours after dosing. A single animal generally showed clinical signs like salivation, rales, reduced activity, piloerection, brown staining on the muzzle, swollen abdomen, difficulty in respiration and pallor until the last day of the observation period. Body weight losses or reduced body weight gain were noted in these animals during the observation period. No mortality occurred in the 3 females subsequently dosed at 50 mg/kg (Step 4). Piloerection, hunched posture and reduced activity were observed up to Day 3. Recovery occurred by Day 4. Body weight and body weight changes observed in these animals were within the expected range for this strain and age of animals at the end of the study. No abnormalities were observed at necropsy examination performed in animals treated at 50 mg/kg (Steps 3 and 4) at the end of the observation period. Abnormal shape (swelling and/or distention) and/or abnormal content (gas) of stomach, duodenum, jejunum, ileum, caecum and colon, as well as small spleen, were observed only in a single animal.

These results indicate that the test item has some toxic effects (including mortality) in the rat following oral administration of a single dose at 300 mg/kg. No mortality nor severe signs of toxicity were observed following dosing at 50 mg/kg. These results indicate the LD50 to be greater than 50 but lower than 300 mg/kg body weight.