Registration Dossier

Administrative data

Description of key information

Oral
Female rats (n=5) received a single oral dose of 2000 mg/kg bw of the test substance. No effects on clinical signs, body weight and macroscopic examinations were observed. Since no mortalities were observed the LD50 was found to be> 2000 mg/kg bw.
Dermal
Rats (5/sex) were treated dermally with 2000 mg/kg bw of the test substance. No mortality, effects on body weight, abnormal clinical observations or macroscopic effects were found in the 14 days observation period. The LD50 is therefore > 2000 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:
15-10-2013 - 18-11-2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to the guideline and GLP
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Female rats, obtained from Charles River Canada, Montreal, Quebec (body weight range 200.2 - 208.0 g [after fasting]) were individually housed in solid bottom cages. Individual animals were identified by colour coding; the animal number and group number also appeared on the outside of each cage to preclude mix-up. The animal room environment was controlled (targeted ranges : temperatures 19 - 25 degrees C, relative humidity 30 - 70%, minimum 10 air changes per hour) and monitored. The photo-cycle was 12 hours light and 12 hours dark. Upon arrival all animals were submitted to a general physical examination and all were found healthy and were admitted. Teklad Certified Rodent Diet and water were offered ad libitum throughout the acclimatization (7 days).

The cage cleaning schedule, air filtration and recirculation, health checks and facility maintenance were carried out in accordance with the applicable Nucro-Technics' Standard Operating Procedures, and such activities were recorded in the animal room records.

Animals were housed and maintained according to the AAALAC International Guide for Care and Use of Laboratory Animals (https://www.aaalac.org/about/guidelines.cfm), CCAC Guidelines for Care and Use of Experimental Animals (http://www.ccac.ca/en_/standards/guidelines) and Nucro-Technics Standard Operating Procedures.

All animals used for the Limit test were fasted overnight. Food, but not water, was withheld beginning at 4.00 pm on the day preceding dosing, and was returned to the cages approximately 1 hour after dosing.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.0 mL/kg bw
Schedule: Since this animal survived, four additional animals were sequentially dosed at 2-day intervals. A total of 5 animals were dosed.
Doses:
2000 mg/kg (limit test)
No. of animals per sex per dose:
5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: individally once during the first 30 minutes of dosing, periodically during the first 24 hours following dosing. Observations were subsequently carried out once daily for the remainder of the study. Cageside observations focused upon any changes in the skin and fur; eyes and mucous membranes; respiratory, circulatory, autonomic and central nervous system and also somatomotor and behavior patterns. Special attention was given to any observation of tremours, convusions, salivation, diarrhoea, lethargy sleep and/or coma.
The body weights were determined prior to test item administration (Day 0), on Day 7 and on Day 14. Body weights gains were calculated.
- Necropsy of survivors performed: yes
This included examination of:
External surfaces of the body, All orifices, Cranial cavity, External surfaces of the brain and spinal cord, Nasal cavity and paranasal sinuses, Thoracic, abdominal and pelvic cavities and viscera.





Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
None
Body weight:
Body weights increased by 65 +/- 16.2 g over 14 days post dosing.
Gross pathology:
No pathalogical findings were observed.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 after oral administration of the test substance is > 2000 mg/kg.
Executive summary:

Female rats (n=5) received a single oral dose of 2000 mg/kg bw of the test substance. No effects on clinical signs, body weight and macroscopic examinations were observed. Since no mortalities were observed the LD50 was found to be> 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Klimisch 1 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:
26 Oct 2014 to 10 Nov 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study according to the guidelines, under GLP
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, NC
- Age at study initiation: ca. 10 weeks
- Weight at study initiation: Males 322-340 g; Females 217-266 g
- Fasting period before study: NA
- Housing: individually in stainless steel, wire-mesh cages suspended above cage-board
- Diet: PMI Nutrition International, LLC, Certified Rodent LabDiet ® 5002 ad libitum
- Water: Municipal water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.3ºC to 21.4ºC
- Humidity (%): 34.8% to 49.2%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Details on dermal exposure:
TEST SITE
- Area of exposure, coverage: 10% of body surface
- Type of wrap if used: gauze binders (<8 ply) that were secured with nonirritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with disposable paper towels moistened with tepid tap water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.01 mL/kg, 2000 mg/kg bw (density 0.997)

VEHICLE: none
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males + 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality 1, 2, and 4 hours post-application on study day 0 and twice daily thereafter
- Necropsy of survivors performed: yes (macroscopy)
- Other examinations performed:
clinical signs: 1, 2, and 4 hours post-application on study day 0 and daily thereafter (includes signs of irritation)
body weight: on day 0, 7 and 14
Statistics:
NA
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
no treatment related effects (no signs of irritation, brown discoloration of the application site)
Body weight:
within normal ranges
Gross pathology:
no abnormalities detected
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the substance after dermal application is > 2000 mg/kg bw.
Executive summary:

Rats (5/sex) were treated dermally with 2000 mg/kg bw of the test substance. No mortality, effects on body weight, abnormal clinical observations or macroscopic effects were found in the 14 days observation period. The LD50 is therefore > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Klimisch 1 study

Additional information

Justification for selection of acute toxicity – oral endpoint
LD50 > 2000 mg/kg bw

Justification for selection of acute toxicity – inhalation endpoint
waiver based on low vapour pressure and no formation of aerosols during use

Justification for selection of acute toxicity – dermal endpoint
LD50 > 2000 mg/kg bw

Justification for classification or non-classification

The available data on acute toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.