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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study according to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Noram O

Test animals

Species:
rat
Strain:
other: Sprague-Dawley, ICO: OFA-SD (IOPS Caw)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Crédeo, 69210 L´Arbresle, France
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: 175 ± 9 g (males); 153 ± 9 g (females)
- Fasting period before study: The day before treatment, the animals were fasted for a period of approx. 18 hours
- Housing: 5 animals of the same sex during the study; they were housed in polycarbonate cages (48x27x20 cm) with stainless steel lid.
- Diet (e.g. ad libitum): ad libitum (except fasting period)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): The air was non-recycled and filtered.
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): The test substance in solution in corn oil was administered at a volume of 10 mL/kg (at the dose levels of 200, 500 and 1000 mg/kg). During the limit test (2000 mg/kg; first experiment), the test substance was administered in its original form (volume: 2.5 mL/kg).
- Lot/batch no. (if required): A 24899 91552
- The test substance was heated at approx. 30 °C and then dissolved in corn oil.



Doses:
First experiment (limit test): 2000 mg/kg
Second experiment: 200, 500, 1000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days or 28 days (at the dose level of 1000 mg/kg) after treatment
- Frequency of observations and weighing: The animals were observed at least once day for 14 days. The animals were individually weighed just before treatment and then on days 5, 8 and 15.
- Necropsy of survivors performed: yes; on day 15 after treatment
- Other examinations performed: clinical signs, body weight, macroscopic examination of the main organs (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen)
Statistics:
The LD50 was calculated according to a Probit Analysis, Finney´s method.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 689 mg/kg bw
95% CL:
472 - 99 999
Sex:
male
Dose descriptor:
LD50
Effect level:
1 200 mg/kg bw
95% CL:
1 027 - 9 110
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 2 000 mg/kg bw
Mortality:
For males:
At 200 mg/kg: 20%
At 500 mg/kg: 0%
At 1000 mg/kg: 40%
At 2000 mg/kg: 80%

For females:
At 200 mg/kg: 0%
At 500 mg/kg: 0%
At 1000 mg/kg: 0%
At 2000 mg/kg: 60%
Clinical signs:
At 200 mg/kg: hypokinesia or/and sedation, piloerection and dyspnoea during 4 hours in all animals; between days 8 and 10, abdominal swelling with associated clinical signs in one male animal
At 500 mg/kg: hypokinesia or sedation, piloerection and dyspnoea during 4 hours; hypokinesia until day 5 in all animals; between days 11 and 13, abdominal swelling in one male and one female animal
At 1000 mg/kg: hypokinesia, sedation, piloerection and dyspnoea during the first two weeks of observation and abdominal swelling from day 4; the clinical signs persisted until day 13 in the females and until day 29 in one male animal
At 2000 mg/kg: hypokinesia, sedation and dyspnoea until day 4 in all surviving animals; from day 5, abdominal swelling and associated clinical signs were observed and regressed totally on day 15
Body weight:
At the doses of 200 and 500 mg/kg, the body weight gain of the surviving animals was slightly lower than normal between days 1 and 5. It returned to normal except in one male and one female animal at the dose of 200 mg/kg.
At the dose of 1000 mg/kg, a body weight loss of the animals was noted between days 1 and 5 and it returned to normal on day 8 in the surviving animals.
At the dose of 2000 mg/kg, a body weight loss of the animals was noted between days 1 and 8 and it returned to normal on day 15 in the surviving animals.
Gross pathology:
Macroscopic examination of the main organs of the animals (found dead during the study or sacrificed at the end of the study) revealed no abnormalities. Due to the absence of macroscopic lesions, no samples were taken for histological examinations.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of this study, the test material is considered to be harmful if swallowed
Executive summary:

In an OECD TG 401 study, the test substance "Noram O" (oleylamine), an opaque, non-homogenous liquid (purity 97.9%), was orally applied to Sprague Dawley rats at a doses of 2000, 1000, 500 and 200 mg/kg bw. In a pre-test (limit test) with 2000 mg/kg bw, no vehicle was used. The substance was heated to approximately 30°C and mixed with corn oil for the lower dose groups in the main test. Mortalities were 70, 20, 0, and 10% in the respective dose groups. Males (LD50 approximately 1200 mg/kg bw) were more sensitive compared to females (LD50 approximately 2000 mg/kg bw); the LD50 for both sexes was established at 1689 mg/kg (probit analysis). Clinical signs included: hypokinesia and/or sedation, piloerection and dyspnea, abdominal swelling. Decreases in body weight gain were noted between day 1 to 5 at 200 and 500 mg/kg bw, persisting in one male and one female at 200 mg/kg bw; and at 1000 mg/kg and returning to normal by day 8. Body weight gain was also decreased at 2000 mg/kg bw from day 1 to 8, returning to normal by day 15. No abnormalities were noted at necropsy