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Toxicological information

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:
From October 12, 1983 to October 27, 1983
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD Guideline 401.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-Propenenitrile, reaction products with 3-amino-1,5,5-trimethylcyclohexanemethanamine
EC Number:
292-053-3
EC Name:
2-Propenenitrile, reaction products with 3-amino-1,5,5-trimethylcyclohexanemethanamine
Cas Number:
90530-15-7
Molecular formula:
C10 H22 N2 . C3 H3 N1
IUPAC Name:
2-Propenenitrile, reaction products with 3-amino-1,5,5-trimethylcyclohexanemethanamine
Test material form:
other: liquid

Test animals

Species:
rat
Strain:
other: BOR: WISW (SPF TNO)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Mean body weight at study initiation: Males - 102.3 g; Females - 101.1 g
- Fasting period before study: 16 h
- Housing: 1 - 5 animals in Type III Makrolon cages
- Diet: RIO complete feed for rats, Ssniff Versuchstier-Diaten GmbH, 4770 Soest, ad libitum
- Water: Tap water ad libitum
- Acclimation period: 4 - 8 d

ENVIRONMENTAL CONDITIONS
- Temperature: 20±1°C
- Humidity: 60%±5%
- Air changes: 15 times/h
- Photoperiod: 12 h light/dark rhythm

IN-LIFE DATES: From: Oct. 12, 1983 To: Oct. 27, 1983

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- Fasting before exposure: 16 h
- Dose volume used: 1.6-3.3 mL/kg
- Rationale for the selection of the starting dose: a preliminary investigation with a small number of animals was carried out from Oct. 3 to Oct. 18, 1983
Doses:
1,580, 1,990, 2,510 and 3,160 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: The onset, type and duration of all symptoms of poisoning, and the time of death, were noted up to 6 h after treatment, and then daily.The animals were weighed before treatment and 1, 7 and 14 d after treatment.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight
Statistics:
LD50 was determined by the method of Litchfield and Wilcoxon, and reported with 95% confidence limits.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 600 mg/kg bw
Based on:
test mat.
95% CL:
> 2 319 - < 2 915
Mortality:
No mortality was observed in animals dosed at 1,580 and 1,990 mg/kg bw, while the next two groups dosed at 2,510 and 3,160 mg/kg bw had 50% and 90% mortality respectively.
Clinical signs:
All the trated animals showed sypmtoms of toxicity. The symptoms which appeared about 30 minutes after administration were ruffled fur, ataxia, prone position, squatting and sedation, together with loss of appetite and reduced body temperature. In the animal at the highest dose which survived the treatment, the symptoms had not completely disappeared at the end of the investigation.
Body weight:
At the two highest doses, the treatment showed a retarding or inhibiting effect on the increase in body weight.
Gross pathology:
On dissection postmortem, reddened mucosa of the stomach and small intestine were found, together with, in some animals, marked paleness of the small intestinal mucosa, and discoloration (sometimes mottled) of the liver, spleen and lung. In the animals which survived the treatment, some of the animals showed mottling of the lungs and reddening of the small intestinal mucosa after the end of the observation period.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results of the study, the oral LD50 of the test substance was 2,600 mg/kg bw .
Executive summary:

A study was conducted to assess the acute toxicity of the test substance to rats according to OECD Guideline 401. The test substance was administered at the following doses: 1,580, 1,990, 2,510 and 3,160 mg/kg bw. The substance was administered by gavage to fasted animals. The administration volume was 1.6-3.3 mL/kg. The observation period following treatment lasted for 14 d. The onset, type and duration of all symptoms of poisoning, and the time of death, were noted up to 6 h after treatment, and then daily. The animals were weighed before treatment and 1, 7 and 14 d after treatment. All the animals sacrificed at the end of the investigation for each dose were dissected and subjected to gross examination, and the findings were recorded. All the treated animals showed symptoms of toxicity. The symptoms which appeared about 30 min after administration were ruffled fur, ataxia, prone position, squatting and sedation, together with loss of appetite and reduced body temperature. In the animal at the highest dose which survived the treatment, the symptoms had not completely disappeared at the end of the investigation. No mortality was observed in animals dosed at 1,580 and 1,990 mg/kg bw, while the next two groups dosed at 2,510 and 3,160 mg/kg bw had 50% and 90% mortality respectively. At the two highest doses, the treatment showed a retarding or inhibiting effect on the increase in body weight. On dissection post-mortem, reddened mucosa of the stomach and small intestine were found, together with, in some animals, marked paleness of the small intestinal mucosa, and discoloration (sometimes mottled) of the liver, spleen and lung. In the animals which survived the treatment, some of the animals showed mottling of the lungs and reddening of the small intestinal mucosa after the end of the observation period. Based on the results of the study, the oral LD50 of the test substance was 2,600 mg/kg bw (Murmann P, 1983a).

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