Registration Dossier

Administrative data

Description of key information

Female rats (n=1) received a single dose of the test substance at 300 and 2000 mg/kg bw in a sighting study. In absence of mortality or signs of toxicity, additional 4 females were dosed at 2000 mg/kg bw. No mortality was observed in these females and no effects on body weight, clinical signs or gross examination were noted. The study followed the fixed dose procedure without any deviations from the guideline. The LD50 is > 2000 mg/kg bw.

Wistar rats (5/sex) were dermally exposed to the substance for 24 hours (semi occlusion) at 2000 mg/kg bw. No mortality, clinical signs or macroscopic changes were seen. Body weight gain was within normal ranges. Most animals showed signs of irritation. The LD50 is > 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:
28-07-2014 to 03-09-2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: guideline study under GLP
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd.,Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 155-195 g
- Fasting period before study: overnight and 3-4 hours after docing
- Housing: ≤ 4 in solid floor polypropylene cages
- Diet: 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK, ad libitum:
- Water: ad libitum:
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): > 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE: arachis oil BP
- Concentration in vehicle: 30 and 200 mg/L
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: test substance did not dissolve/suspend in distilled water

Doses:
sighting dose: 300 and 2000 mg/kg bw
main study: 2000 mg/kg bw
No. of animals per sex per dose:
sighting study: 1 female/dose
main study: 4 females at 2000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Body weight: at study start and weekly thereafter
- Clinical signs: ½, 1, 2, and 4 hours after dosing and then daily for 14 days
- Mortality/morbidity: twice daily
- Necropsy : macroscopic examination
Statistics:
NA
Preliminary study:
No mortality or signs of toxicity in females at 300 and 2000 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
none
Clinical signs:
1 female at 300 mg/kg bw: hunched posture 2 hours after dosing
Body weight:
within expected ranges
Gross pathology:
no abnormalities
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the testsubstance is > 2000 mg/kg bw
Executive summary:

Female rats (n=1) received a single dose of the test substance at 300 and 2000 mg/kg bw in a sighting study. In absence of mortality or signs of toxicity, additional 4 females were dosed at 2000 mg/kg bw. No mortality was observed in these females and no effects on body weight, clinical signs or gross examination were noted. The study followed the fixed dose procedure without any deviarions from the guideline. The LD50 is > 2000 mg/kg bw.

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

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:
21-01-2015 to 04-02-2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: study according to the guideline under GLP
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Strain: Wistar (RccHan™:WIST)
- Age at study initiation: 8-12 weeks
- Weight at study initiation: males: 234-250 g; females 206-220 g
- Housing: during 24 h exposure period individually, thereafter 5/sex/cage (suspended solid floor polypropylene cages furnished with woodflakes)
- Diet: 2014C Teklad Global Rodent diet ad libitum
- Water: ad libitum
- Acclimation period: ≥ 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): 30-70%
- Air changes (per hr): ≥ 15/hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure ( % coverage) : 10%
- Type of wrap if used: surgical gauze semi-occluded with a piece of self-adhesive bandage

REMOVAL OF TEST SUBSTANCE: after 24 h exposure treated skin and surrounding hair was wiped with cotton wool moistened with arachis oil BP

Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Body weight: at study start and weekly thereafter
- Clinical signs: 1/2, 1, 2, and 4 hours after exposure and then daily for 14 days
- Irritation: after removal of the dressing and daily for 14 days
- Mortality/morbidity: twice daily
- Necropsy : macroscopic examination
Statistics:
NA
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
None
Body weight:
body weight gain within normal ranges
Gross pathology:
no effects
Other findings:
Signs of skin irritation in 3 males and all females (very slight to well-defined erythema, very slight oedema, crust formation, hemorrhage of dermal capillaries, small superficial scattered scabs and scab lifting to reveal glossy skin)
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 for dermal toxicity is > 2000 mg/kg bw
Executive summary:

Wistar rats (5/sex) were dermally exposed to the substance for 24 hours (semi occlusion) at 2000 mg/kg bw. No mortality, clinical signs or macroscopic changes were seen. Body weight gain was within normal ranges. Most animals showed signs of irritation. The LD50 is > 2000 mg/kg bw

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

Additional information

No toxicity was observed after a single exposure to the test substance. The LD50 values after oral and dermal exposure were > 2000 mg/kg bw.

Justification for classification or non-classification

Based on the outcome of the available studies the substance is not classified as hazardous accordingto Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.