Dimethyl(octyl)amine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 January 1996 - 13 September 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl(octyl)amine

EC Number:

230-939-3

EC Name:

Dimethyl(octyl)amine

Cas Number:

7378-99-6

Molecular formula:

C10H23N

IUPAC Name:

dimethyl(octyl)amine

Details on test material:

Name: AD 1
Chemical Name: N, N-Dimethyloctylamine
CAS No.: 7378-99-6
Batch No.: 13602808
Expiry Date: not applicable
Physical State at Room Temperature: liquid
Colour: clear
Volatility: volatile
Density: 0.765
Molecular Weight: 157.3
Active Components: > 95%
Structure Formula of
Active Component: C8H17-N-(CH3)2
Storage Conditions: at room temperature

Specific details on test material used for the study:

The test material was prepared at appropriate concentrations in maize oil to permit administration at a constant volume-dosage of 10 ml/kg bodyweight
Dosages were calculated and expressed gravimetrically in terms of the material as received. Fresh formulations of the test material were prepared on the morning of administration and any surplus remaining after dosing was disposed of on the same day.
No analyses were undertaken to assess the stability, homogeneity or achieved concentrations of the test material in the vehicle.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

The animals were housed in stainless steel grid cages (RS Biotech, Northants, England). The grid floor ensured rapid removal of waste material to undertrays which were cleaned as necessary. Five animals of the same sex were accommodated in each cage, unless reduced by mortality. The cages were suspended in mobile stainless steel racks.
The animals were held in a limited-access facility. All rooms were kept at slight positive pressure relative to the outside and each had its own filtered air supply giving at least 10 complete air changes per hour without re-circulation. Target values for temperature and humidity were 21°C (range 19°-25°C) and 55% R.H (range 40%-70% R.H.), respectively. The achieved values were monitored daily. Electric time-switches regulated a lighting cycle of 12 hours of artificial light per day. An emergency generator was available to maintain the electricity supply in the event of a power failure. All personnel entering the building changed into clean protective clothing and wore an oversuit, gloves, plastic over-shoes and face mask to service animal holding areas. A commercially-available complete pelleted rodent diet (RMl(E) SQC, from Special Diets Services Limited, Witham, Essex, England) was fed ad libitum. The manufacturer supplied analytical data with each batch of diet which included concentrations of nutritional components, aflatoxins and selected
heavy metals, pesticides and micro-organisms. The diet contained no added antibiotic or other chemotherapeutic or prophylactic treatment. Samples of diet were taken for analysis at six-monthly intervals to detect potential contaminants by a laboratory independent of the supplier. Results of these analyses are retained in the archives.
Animals had free access to tap water taken from the public supply; in England the supply and quality of this water is governed by Department of the Environment regulations. Certificates of analysis were routinely received from the supplier (Essex and Suffolk Water pie). At approximately six-month
intervals water was routinely sampled for analysis, by a laboratory independent of the supplier, for selected chlorinated and organophosphorus pesticides, polychlorinated biphenyls and lead and cadmium contaminants; it was also examined for coliform bacteria. Results of these analyses are retained in the archives.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

maize oil

Details on oral exposure:

A preliminary study was carried out using two groups of one male and one female rat given an oral administration of AP-1 at dosages of 500 and 2000 mg/kg, at a constant volume-dosage of 10 ml/kg in maize oil.

Dose-volume was determined for each animal according to the fasted bodyweight on the morning of dosing. The dose was administered on Day 1 at a constant volume-dosage of 10 ml/kg bodyweight.
A flexible catheter was passed down the oesophagus allowing instillation of the dose into the lumen of the stomach. Each animal was returned to its cage and food hoppers were re-filled approximately three hours after dosing.

Doses:

the main study was carried out using a single group of five male and five female rats given an oral administration of AP-1 at the dosage of 50 mg/kg, at a constant volume dosage of 10 ml/kg in maize oil. Since no animal died a further group of five male and five female rats were treated at 500 mg/kg.

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

Three separate recordings of signs were made during the first hour after dosing and two further recordings during the remainder of Day I. From Day 2 onwards, the animals were inspected twice daily and recordings were made once daily. The circumstances of any death were recorded. Any animal showing severe or enduring signs of pain or distress was humanely killed. The bodyweight of each animal was recorded on the day before dosing and on Days I, 8 and 15. The test was terminated on the morning of Day 15.

Results and discussion

Preliminary study:

A preliminary study was carried out using two groups of one male and one female rat given an oral administration of AD-1 at dosages of 500 and 2000 mg/kg, at a constant volume-dosage of 10 ml/kg in maize oil.

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

ca. 162 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Slope - 80 degrees

Effect levels 2

Key result

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

ca. 382 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Slope - 72 degrees

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

ca. 342 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Slope - 73°

Mortality:

Four male and five female animals treated at 500 mg/kg died on the day of dosing. There was no death amongst the animals treated at 50 mg/kg.

Clinical signs:

other: Ante mortem signs were restricted to prone posture in one female animal. The surviving animal treated at 500 mg/kg showed underactivity, staggering gait, hunched posture and piloerection; it was overtly normal after the first over night period. There was

Gross pathology:

Necropsy of the decedents revealed areas of fur staining and cases of distension of the small intestine by a yellow viscous fluid. There was no macroscopic abnormality detected amongst the surviving animals.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The test article, when administered by gavage, oral to male albino rats, has an estimated acute oral LD50 of 382 mg/kg bw with a slope of 72°.
The test article, when administered by gavage, oral to female albino rats, has an estimated acute oral LD50 of 162 mg/kg bw with a slope of 80°.
162 mg/kg bw is used for catergorising under GHS.

Executive summary:

The acute oral toxicity of AD-1 was investigated in two groups of five male and five female CD rats. The animals were starved overnight prior to dosing. The test material was administered at dosages of 50 and 500 mg/kg, at a constant volume-dosage of 10 ml/kg in maize oil. Mortality and signs of reaction to treatment were recorded during a subsequent 14-day observation period; the surviving animals were killed on the following day. All animals were subjected to necropsy.

The mortality distribution was as 4/5 males and 5/5 at 500 mg/kg bw. No mortality at 50 mg/kg bw. The deaths occurred on on the day of dosing.

Ante mortem signs comprised prone position. Signs of reaction in the surviving animal treated at 500 mg/kg comprised underactivity, staggering gait, hunched posture and piloerection. There was no sign of reaction to treatment amongst the animals treated at 50 mg/kg.

All surviving animals achieved anticipated bodyweight gains.

Necropsy findings for the decedents were unremarkable. There was no macroscopic abnormality evident amongst animals treated at 50 mg/kg.

Under the conditions of this study the acute oral median lethal dosage (LD50), of the test material was approximately 162 mg/kg in female animals.

Accordingly, AD-1 was assigned to Catergory 3.