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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:
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 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:
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.
Body weight:
Slightly depressed body-weight gain in survivors during the first week.
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.