2-Propenenitrile, reaction products with 3-amino-1,5,5-trimethylcyclohexanemethanamine

Endpoint summary

Description of key information

The test substance is considered to be of low acute oral toxicity with LD50 value 2,600 mg/kg bw .

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

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.

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

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

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.

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:

other: 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 ani

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.

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 600 mg/kg bw

Quality of whole database:

High quality

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute toxicity: oral

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).

Acute toxicity: dermal and inhalation

As per Annex VIII of the REACH regulation, acute toxicity studies do not generally need to be conducted if the substance is classified as corrosive to the skin. In this case, the test substance has been classified as corrosive, hence the requirements for dermal and inhalation studies are being waived.

Justification for selection of acute toxicity – oral endpoint
Guideline-compliant study conducted according to GLP

Justification for classification or non-classification

Oral route:

Based on the results of an acute oral toxicity study, the test substance does not need to be classified for this endpoint according to the EU CLP criteria (EC 1272/2008).