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Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
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

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction products of acrylonitrile and 2-methylcyclohexane-1,3-diamine and 4-methylcyclohexane-1,3-diamine, hydrogenated
EC Number:
948-816-4
Molecular formula:
C13H30N4
IUPAC Name:
Reaction products of acrylonitrile and 2-methylcyclohexane-1,3-diamine and 4-methylcyclohexane-1,3-diamine, hydrogenated
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

Test animals

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

Administration / exposure

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Fasting period: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.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.

Results and discussion

Effect levels
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).

Applicant's summary and conclusion

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).

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