Registration Dossier

Administrative data

Description of key information

The LD50(rat, oral) was determined to be between 200 and 2000 mg/kg for males and females.

The LD50(rat, dermal) was determined to be > 2000 mg/kg for males and females.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
Bi-distilled water.
Details on oral exposure:
Concentration in vehicle: 0.2 g/mL or 0.02 g/mL
Total volume applied: 10 mL/kg bw
Doses:
3 females dosed at 2000 mg/kg bw; 3 females dosed at 200 mg/kg bw; 3 males dosed at 200 mg/kg bw.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
All animals were fasted sixteen to twenty hours before dosing and three hours after dosing.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 200 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
3 f at 2000, 0 f+m at 200 mg/kg dw
Clinical signs:
In females administered 2000 mg/kg bw, ventral recumbency and marked sedation were observed in one animal during the first hour after treatment. This animal died two hours after treatment. A second animal showed slight sedation during the first two hours after treatment and moderate sedation during the second hour. The same animal showed slight and moderate ruffled fur in the second and third hours after treatment, respectively, hunched posture in the third hour after treatment, and died four hours after treatment. The third animal showed mild sedation during the first through fifth hour after treatment and ruffled fur from the second through fifth hour after treatment, and was found dead on the second day after treatment.
No clinical signs were observed in females administered 200 mg/kg bw.
In males give a dose of 200 mg/kg bw, one animal showed mild ruffled fur during the second and third hours after treatment. No other clinical signs were observed.
Body weight:
All bodyweights were within the range commonly recorded for this strain and age.
Gross pathology:
Females at 2000 mg/kg bw: Animals that died in the first and fifth hour showed distended stomach and black-brown contents of jejunum. The animal found dead on the second day showed distended stomach.
Females and males at 200 mg/kg bw: No macroscopic findings were observed.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 for both males and females was between 200 and 2000 mg/kg bw.
Executive summary:

The test substance was administered once by gavage to three groups of three rats each following approximately 16 to 20 hours of fasting. Dose levels were 2000 mg/kg bw and 200 mg/kg/bw to females and 200 mg/kg bw to males, all in 10 mL/kg bw. Clinical observations were made 1, 2, 3, and 5 hours after dosing and daily thereafter until termination on Day 15. Bodyweights were recorded on days 1, 8, and 15. Gross necropsies were performed on all animals.

All animals died at 2000 mg/kg bw, no mortality was observed at 200 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed

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:
2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: HanBrl:WIST (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
Age at study initiation: Males, 9 weeks; Females, 12 weeks.
Weight at study initiationMales: 229.3 to 248.9 g. Females: 197.5 to 216.5 g.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Area covered: Approximately 10% of body surface.
Duration of exposure:
Duration of exposure 24 hours.
Postexposure period: 14 days. Skin flushed with lukewarm tap water and dried with disposable paper towels.
Doses:
2.0 mL/kg bw.
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
Clinical signs and mortality
Mortality: Animals were observed twice daily from Day 1 (pre-administration) through Day 15.
Clinical Signs: Animals were observed at least four times on Day 1 after administration, and once daily on Days 2 through 15.

Irritation: Animals were observed at least four times on Day 1 after administration, and once daily on Days 2 through 15.
Bodyweight: Day 1 (pre-administration), 8, and 15.
Necropsy: After sacrifice, all animals were examined macroscopically.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 mL/kg bw
Based on:
test mat.
Mortality:
No animals died.
Clinical signs:
None observed.
Body weight:
The body weights of all animals were within the range commonly recorded for this strain and age.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Slight, moderate, and marked erythema maculata, slight and moderate scales, slight and marked crusts, yellow skin on the back and test item residuals were evident in males and females between Day 2 and Day 15. Refer to Table 1 below.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The acute dermal median lethal dose (LD50) of the test material in rats was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

A GLP-compliant acute dermal toxicity (limit) study was conducted according to OECD Guideline 402 and Directive 92/69/EC, B.3 without deviation. Five male and five female HanBrl: Wist (SPF) strain rats were dosed at 2.0 mL/kg bw with undiluted test material that contained 95% active substance. Clinical signs and bodyweight development were unafffected during the study. The acute dermal median lethal dose (LD50) of the test material in rats was found to be greater than 2000 mg/kg bodyweight. 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

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 (EC) No 1272/2008. Based on these data, the test item is classified for acute oral toxicity (Cat. 4, H302) and not classified for acute dermal and inhalation toxicity according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.