Reaction mass of pentadecylamine and tridecylamine and 2-Methyldodecylamine and 2-Methyltetradecylamine

Endpoint summary

Description of key information

The LD50 for oral toxicity is 1300 mg/kg bw (RL2, rat).

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study based on national and scientific standards, basic data given, acceptable for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: CFY strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 100 - 120 g
- Fasting period before study: overnight

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 4 mL/kg bw

Doses:

0, 1.0, 1.6, 2.5, and 4 mL/kg bw (~800, 1300, 2000, and 3200 mg/kg bw)

No. of animals per sex per dose:

3

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Calculation of the LD50 and 95% C.I. based on Litchfield and Wilcoxon, J. Pharmac. Exp. Ther., 96, 99-113 (1949)

Preliminary study:

Preliminary range finding study was conducted on 2 animals per dose group (one male and one female) at 0, 1.0, and 4.0 mL/kg bw. Only in the highest dose group mortality was observed in both rats < 21 hourse after dosing.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1.6 mL/kg bw

Based on:

test mat.

95% CL:

>= 1.1 - <= 2.2

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 300 mg/kg bw

Based on:

test mat.

95% CL:

ca. 880 - ca. 1 760

Remarks on result:

other: Estimates using a density of 0.8 g/mL

Mortality:

Death occurred from within 21 to 70 h of treatment. Autopsy revelaed darkenning of the liver and kidneys and injection of mesenteric blood vessels.

Clinical signs:

other: Shortly after dosing: lethargy, piloeerection, diuresis, diarrhea, increased salivation, and fine body tremor; later on: additionally ataxia at 1.6 and 2.5 mL/kg bw and lacrimation at 2.5 mg/kg bw.

Gross pathology:

Darkening of livers and kidney and injection of mesenteric blood vessels.

Summary of Mortality Data (from Report, Tab. 2)

Dose [mL/kg bw]	Male rats	Female rats	Total
	Absolute number of deaths
0	0/3	0/3	0/6
1.0	0/3	1/3	1/6
1.6	2/3	1/3	3/6
2.5	3/3	3/3	6/6
4.0	3/3	3/3	6/6

Time of death after dosing:

Men:

1.6 mg/kg: < 70 h

2.5 mg/kg; < 46 h

4.0 mg/kw: < 22 h

Women:

1.0 mg/kg: < 46 h

1.6 mg/kg: < 22 h

2.5 mg/kg; < 51 h

4.0 mg/kw: < 22 h

Evaluation of Bodyweight after dosing in g

Sex	Dosage in mL/kg	Bodyweight at Dosing in g	Bodyweight after 1 week in g	Bodyweight after 2 weeks in g
male	0	107	185	231
	1.0	113	153	209
	1.6	112	152	210
	2.5	111	Died	-
	4.0	111	Died	-
femal	0	106	162	185
	1.0	111	139	174
	1.6	112	136	167
	2.5	115	Died	-
	4.0	110	Died	-

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Based on the experimental data an oral LD50 of 1.6 mL/kg bw was calculated for males and females resulting in an LD50 of around 1300 mg/kg bw.

Executive summary:

The acute toxicity of the test item was investigated (n= 3 males and females per dose group). Rats received single undiluted oral doses of the test item by oral intubation and were observed for 14 days thereafter. Clinical signs like lethargy, piloeerection, diuresis, diarrhea, increased salivation, and fine body tremor were observed shortly after dosing. These signs were later accompanied by ataxia at 1.6 and 2.5 mL/kg bw and by increased lacrimation at 2.5 mg/kg bw.

Death occured from within 21 to 70 hours of treatment. Autopsy revealed darkening of the liver and kidneys and injection of mesenteric blood vessels.

Recovery of survivors, as judged by external appearance and behaviour, was apparently complete within five days of treatment. Slightly depressed bodyweight gains were observed during the first week of observation, but returned to normal during the second week, compared with controls.

Terminal autopsy findings were normal.

Based on the experimental data an oral LD50 of 1.6 mL/kg bw was calculated for males and females resulting in an LD50 of around 1300 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 300 mg/kg bw

Additional information

In one experimental study male CFY rats (3 rats/sex/dose) were subjected to test acute oral toxicity. The test item (purity not mentioned) was administered by gavage to animals in 4 different dose levels and were observed for further 14 days. The results obtained led to a LD50 = 1300 mg/kg bw (Kynoch et al., 1975). This reliable study was selected as key study.

Another reliable experimental study performed (RL 1; according to OECD 401, limit dose test) in rats result in a slightly higher LD50 of > 2000 mg/kg bw (Jensch, 1997). Here the oral toxicity of the test item was tested only at a dose level of 2000 mg/kg bw. The animals received the compound as a 20 % solution in sesame oil, the administration volume being 10 mL/kg bw.

Justification for classification or non-classification

Based on the requirements of Regulation (EC) No 1272/2008 and an oral LD50 of 1300 mg/kg bw in experimental animals C13/C15 amine should be classified as acutely oral toxic category IV, H302.