reaction mass of N1,N3-bis(3-aminopropyl)-2-methyl-cyclohexane-1,3-diamine and N1,N3-bis(3-aminopropyl)-4-methyl-cyclohexane-1,3-diamine

Endpoint summary

Description of key information

LD50, oral, rat >300 < 2000 mg/kg bw (BASF, 2018)

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:

Jan 2018 - May 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Specific details on test material used for the study:

Batch identification: Bähr63/Dest/F4-5
Test item No.: 17/0592-1
Physical state / color: Liquid / colorless to yellowish, clear

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Young adult animals (female animals approx. 10 weeks)

Acclimatization period of at least 5 days before the beginning of the experimental phase; during the acclimatization period, the animals were accustomed to the environmental conditions of the study and to the diet

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Route of administration: Single oral administration by gavage.
Fasting period: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
Time of day of administration: In the morning
Observation period: 14 days

Doses:

300, 2000 mg/kg bw/d

No. of animals per sex per dose:

3 females/dose

Control animals:

no

Details on study design:

For the high dose, the liquid test item was administered unchanged. For the lower dose, an administration volume of 2 ml/kg bw of suitable test item preparations was used to facilitate administration.

Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and on the day of death on study day 1.
Clinical observations: Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
Mortality: A check for any dead or moribund animals was made at least once each workday; these records are archived by Bioassay.
Pathology: Necropsy with gross-pathology examination was performed on the last day of the observation period after sacrifice by CO2-inhalation in a chamber with gradually increasing concentrations. Necropsy of all animals that died as early as possible after death.
Histology: No histological examinations were performed.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

In the 2000 mg/kg bw test group all animals died within hour 1, 4 or day 1 after administration, respectively.

No mortality occurred in both 300 mg/kg bw test groups.

Clinical signs:

In the 2000 mg/kg bw test group impaired general state was seen in all animals at hour 0, hour 1 or from hour 1 until hour 2 after administration. Impaired general state progressed to poor general state was seen in two out of three animals at hour 3 or from hour 2 until hour 5.
Dyspnoea and piloerection were observed in all animals at hour 0 or from hour 1 until hour 3 or 5 after administration.
Abdominal position was seen in one animal at hour 3, while cowering position was seen noted in another animal from hour 2 until hour 5. In this animal apathy was noticed from hour 4 until hour 5 after administration.

In the first 300 mg/kg bw test group impaired general state and piloerection were noticed observed in all animals from hour 3 until hour 4 or 5 after administration.

In the second 300 mg/kg bw test group impaired general state, dyspnoea and piloerection were noticed in all animals from hour 1 or 2 until hour 5 after administration. Cowering position was seen in two of these animals at hour 4 and persisted in one of these animals until hour 5 after administration.

Body weight:

The body weight of the surviving animals increased within the normal range throughout the study period.

Gross pathology:

The following macroscopic pathologic findings were observed in the animals that died in the 2000 mg/kg bw test group:
o Red discoloration of the glandular stomach in all animals
o Red discoloration of the stomach contents in all animals
o Red discoloration of the small intestine in two animals
o Dark spotted discoloration of the liver in all animals
o Congestion of the kidneys in one animal
o Dark discoloration of the spleen in two animals

There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period (300 mg/kg bw: 6 females).

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

Under the conditions of this study the median lethal dose of Reaction mass of N1,N3-bis(3-aminopropyl)-2-methyl-cyclohexane-1,3-diamine and N1,N3-bis(3-aminopropyl)-4-methyl-cyclohexane-1,3-diamine after oral administration was found to be greater than 300 mg/kg bw and less than 2000 mg/kg bw in rats.

Executive summary:

Under the conditions of this study the median lethal dose of Reaction mass of N1,N3-bis(3-aminopropyl)-2-methyl-cyclohexane-1,3-diamine and N1,N3-bis(3-aminopropyl)-4-methyl-cyclohexane-1,3-diamine after oral administration was found to be greater than 300 mg/kg bw and less than 2000 mg/kg bw in rats (BASF, 2018).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In an acute oral toxicity study performed according to the Acute Toxic Class Method, doses of 2000 and 300 mg/kgbw of the testitemReaction mass of N1,N3-bis(3-aminopropyl)-2-methyl-cyclohexane-1,3-diamine and N1,N3-bis(3-aminopropyl)-
4-methyl-cyclohexane-1,3-diamine(undiluted orpreparations in deionized water) were administered by gavage to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 3 females, 300 mg/kg bw in 6 females).

Under the conditions of this study the median lethal dose ofReaction mass of N1,N3-bis(3-aminopropyl)-2-methyl-cyclohexane-1,3-diamine and N1,N3-bis(3-aminopropyl)-4-methyl-cyclohexane-1,3-diamineafter oral administration was found to begreater than 300 mg/kg bw and less than 2000 mg/kg bw in rats.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance need to be classified and labelled as acute oral category 4 under Regulation (EC) No 1272/2008