Registration Dossier

Administrative data

Description of key information

Under the conditions of an OECD 423 compliant GLP study the median lethal dose of the test item after oral administration was found to be greater than 500 mg/kg and less than 2000 mg/kg body weight in female rats.

LD50 (oral) > 500 mg/kg < 2000 mg/kg bw/d (OECD 423, BASF 2005)

LD50 (dermal) > 2000 mg/kg bw/d (OECD 402, BASF 2018)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
500 mg/kg bw
Quality of whole database:
GLP and guideline study.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03/2018 - 06/2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Specific details on test material used for the study:
Test item No.: 13/0241-4
Batch identification: 16315004
CAS No.: 93940-97-7
Purity: 96.1 area-% (mixture of isomers)
Homogeneity: The test item was homogeneous by visual inspection.
Storage stability: The stability of the test item under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
Expiry date: May 01, 2019
Storage conditions: Ambient (RT)
Physical state/ color: Liquid / yellowish, clear
Density [g/mL]: 0.986 (determined by Bioassay Laboratories)
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Age on day 0: Young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks)
Body weight on day 0: Animals of comparable weight (± 20% of the mean weight)

Room temperature / relative humidity: The animals were housed in fully air-conditioned rooms. Central air-conditioning guaranteed a range of 22°C  3°C for temperature and of 30 – 70% for relative humidity. There were no deviations from these ranges, which influenced the results of the study.
Air changes per hour: Approx. 10
Day / night rhythm: 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)
Type of cage: Makrolon cage, type III
Number of animals per cage: Single housing
Feeding: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
Drinking water: Tap water ad libitum
Bedding: H 15005-29; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)
Enrichment: Wooden gnawing blocks (Type NGM E-022) ; ABEDD® LAB & VET Service GmbH, Hasnerstraße 84/6; 1160 Wien – Austria
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Route of application: Single application to the clipped skin (dorsal and dorsolateral parts of the trunk); covering of the application site with a semi-occlusive dressing* for 24 hours. Afterwards removal of the semi-occlusive dressing, rinsing of the application site with warm water
Application area: About 40 cm² (corresponds to at least 10% of the body surface)
Duration of exposure:
24 hours
Doses:
limit dose: 2000 mg/kg bw
No. of animals per sex per dose:
5
Details on study design:
Observation period: 14 days

Body weight determination: Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation.

Clinical observations: Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter.

Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter /several times until the last day of observation / and on the last day of observation.

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.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Systemic effects:
No systemic clinical signs were observed during clinical examination in male and female.

Local effects:
Male: moderate erythema (grade 2) was seen in four male animals from study day 1 until study day 3 and persisted in one of these animals until study day 10. Furthermore, incrustations were observed in four male animals from study day 2 until study day 3 and persisted in one of these animals until study day 10.

Female: Moderate erythema (grade 2) was seen in four female animals from study day 1 until study day 3 and persisted in one of these animals until study day 10. Furthermore, incrustations were observed in three female animals from study day 2 until study day 3, while in one of these animals scaling was noticed from study day 6 until study day 10.
Body weight:
All animals gained weight in a normal range throughout the study period.
Gross pathology:
No macroscopic pathologic abnormalities were noted in any animal examined on the last day of observation (5 males and 5 females).
Conclusions:
In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item 3-[[3-[[(2-cyanoethyl)amino]methyl]-3,5,5- trimethylcyclohexyl]amino]propiononitrile to the clipped application site (dorsal and dorso-lateral parts of the trunk and covered by semi-occlusive dressing during the 24-hour exposure period. The application area comprised at least 10% of the total body surface. The animals were observed for 14 days.
- No mortality occurred
- No signs of systemic toxicity were observed
- The following test item-related local skin effects were recorded during the course of the study, local effects occurred within 10 days after application:
- Well-defined erythema (grade 2)
- Incrustations
- Scaling
- All animals gained weight in a normal range throughout the study period.
- No macroscopic pathologic abnormalities were noted in any animal examined at the end of the study (5 males and 5 females).
Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw
Executive summary:

Under the conditions of this study the median lethal dose (LD50) of 3-[[3-[[(2-cyanoethyl)amino]methyl]-3,5,5- trimethylcyclohexyl]amino]propiononitrile after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
GLP and guideline study.

Additional information

Acute toxicity oral:

The study was performed to assess the acute toxicity following oral administration of the test item in Wistar rats. Single doses of 2000 and 500 mg/kg body weight of test material preparations in olive oil Ph.Eur./DAB were given to 3 administration groups of three fasted female animals, each, (2000 mg/kg in 3 females, 500 mg/kg in 6 females) by gavage in a sequential manner. Two animals of the 2000 mg/kg administration group were found dead, one on study day 1 and one on day 8. No mortality occurred in the 500 mg/kg administration groups. Clinical observation in the 2000 mg/kg bw administration group revealed impaired general state, dyspnoea, staggering, tremor, piloerection, smeared fur, salivation and red clammy snout. Findings were observed from hour 0 until including study day 9 after administration. No clinical signs and findings were observed in the 500 mg/kg bw administration groups. The body weight of the surviving animal of the 2000 mg/kg bw administration group and the mean body weights of the animals of the 500 mg/kg bw administration groups increased throughout the study period. No macroscopic pathologic abnormalities were noted in the animals that died and in the surviving animals of all administration groups examined at the end of the observation period. Under the conditions of this study the median lethal dose of the test item after oral administration was found to be greater than 500 mg/kg and less than 2000 mg/kg body weight in rats.

Acute toxicity dermal:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item 3-[[3-[[(2-cyanoethyl)amino]methyl]-3,5,5- trimethylcyclohexyl]amino]propiononitrile to the clipped application site (dorsal and dorso-lateral parts of the trunk and covered by semi-occlusive dressing during the 24-hour exposure period. The application area comprised at least 10% of the total body surface. The animals were observed for 14 days.

- No mortality occurred

- No signs of systemic toxicity were observed

The following test item-related local skin effects were recorded during the course of the study, local effects occurred within 10 days after application:

- Well-defined erythema (grade 2)

- Incrustations

- Scaling

- All animals gained weight in a normal range throughout the study period.

- No macroscopic pathologic abnormalities were noted in any animal examined at the end of the study (5 males and 5 females).

Accordingly, the acute dermal median lethal dose (LD50) was determined to be LD50, dermal, rat > 2000 mg/kg bw

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 needs to be classified and labelled as harmful after acute oral administration (GHS, cat. 4, H302) under Regulation (EC) No 1272/2008.