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Description of key information

Oral (OECD 423), rat: LD50  ≥ 5000 mg/kg bw (limit test)
Dermal (OECD 402), rat: LD50 > 5000 mg/kg bw (limit test)

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:
08 - 28 Oct 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
other: Crl:CD(SD), SPF
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks
- Weight at study initiation: 179.4 - 199.9 g
- Fasting period before study: Animals were fasted overnight, approx. 16 h prior and for approx. 4 h after dosing.
- Housing: 1 animal per cage in stainless wire mech cages (260W x 350D x 210H mm)
- Diet: Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C (Harlan Laboratories, Inc., USA), ad libitum
- Water: public tap water filtered and irradiated by ultraviolet light, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.8 - 22.3
- Humidity (%): 48.3 - 54.1
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min and 1, 2, 4 and 6 h after dosing and thereafter once daily for 14 days. Individual body weights were recorded prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy, Day 14.
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Abnormal gait was evident in 2 animals at 1 and 2 h after dosing. The sign disappeared 4 h after dosing.
Body weight:
All animals showed expected gains in body weight over the study period
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study in rats a LD50 cut-off value of ≥ 5000 mg/kg bw was found.
Executive summary:

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 423 and in compliance with GLP (2015a). In a first step, a total dose of 2000 mg/kg bw of the test substance diluted in corn oil was administered to 3 female rats. Animals were observed 0.5, 1, 2, 4 and 6 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy, Day 14. Macroscopic examination was performed at the end of the observation period at terminal sacrifice. In a second step, 3 additional female rats were treated with 2000 mg/kg bw of the test substance diluted in corn oil. No mortalities were observed at 2000 mg/kg bw until the end of the study. Abnormal gait was evident in 2 animals at 1 and 2 hours after dosing. The sign disappeared 4 hours after dosing. All animals showed expected gains in body weight over the study period and no abnormalities were noted at necropsy. Based on the results of this study, the LD50 value was determined to be > 2000 mg/kg bw in rats. In accordance with OECD Guideline 423, Annex 2d, a cut-off value of5000 mg/kg bw was derived, since no mortality occurred at 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study, and is thus sufficient to fulfill the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:
22 Oct - 06 Nov 2015
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
occlusive conditions
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
yes
Remarks:
occlusive instead of semi-occlusive conditions
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
other: Crl:CD(SD), SPF
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 8 weeks (males), 9 weeks (females)
- Weight at study initiation: 270.3 - 285.4 g (males), 215.4 - 248.0 (females)
- Housing: individually in stainless wire mech cages (260W x 350D x 210H mm)
- Diet: Teklad Certified Irradiated Global 18% Protein Rodent Diet 2918C (Harlan Laboratories, Inc., USA), ad libitum
- Water: public tap water filtered and irradiated by ultraviolet light, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9 - 22.6
- Humidity (%): 46.9 - 56.0
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
A preliminary study was conducted to select the dose level for the main study.

TEST SITE
- Area of exposure: skin of the subscapular dorsal surface (approx. 5 cm x 6 cm)
- Type of wrap if used: After the application of the test substance to a lint tape, the application site was covered with the lint tape and plastic film. The back of the animals was over-wrapped with Soft Cloth Tape with Liner (5 cm width) and surgical tape.The application site of control animals was covered with the lint tape, plastic film and Soft Cloth Tape with Liner and surgical tape in the same manner as dosed animals.

REMOVAL OF TEST SUBSTANCE
- Washing: Any residual test substance was removed using absorbent cotton moistened with tepid water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 4.98 mL/kg bw
- Constant concentration used: yes
Duration of exposure:
24 h
Doses:
Preliminary study: 5000 mg/kg bw
Main study: 0 and 5000 mg/kg bw
No. of animals per sex per dose:
Preliminary study: 1 male and 1 female
Main study: 5 males and 5 females
Control animals:
yes, concurrent no treatment
Details on study design:
Preliminary study:
- Duration of observation period following administration: 3 days
- Frequency of observations: Individual body weights were recorded on the day of treatment and on Day 3.
- Necropsy of survivors performed: no

Main study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min and 1, 2, 4 and 6 h after dosing and thereafter once daily for 14 days. Individual body weights were recorded prior to dosing on Day 0 and on Days 3, 7 and on the day of necropsy, Day 14.
- Necropsy of survivors performed: yes
Statistics:
Statistical analysis was performed using SAS Program (version 9.3). Body weights were analyzed utilizing Folded-F test for homogeneity of variance (significance level: 0.05). Student t-test was employed on homogeneous data (significance level: 0.05) or Aspin-Welch t-test was employed on heterogeneous data (significance level: 0.05) for confirming significance (significance levels: 0.05 and 0.01, two-tailed), respectively.
Preliminary study:
No deaths or clinical signs of toxicity were noted at 5000 mg/kg bw throughout the 3-day observation period. The dose level selected for the main study was therefore 5000 mg/kg bw.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period of the main study.
Clinical signs:
No signs of systemic toxicity were noted during the main study.
Body weight:
All animals showed expected gains in body weight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute dermal toxicity study a LD50 value > 5000 mg/kg bw in male and female rats was found.
Executive summary:

The acute dermal toxicity of the test substance was assessed in a study according to OECD Guideline 402 and in compliance with GLP (2015b). In a preliminary study, 1 male and female rat, respectively, were treated dermally with 5000 mg/kg bw test substance. Since no mortality was observed at 5000 mg/kg bw this dose level was selected for the main study. In the main study, 5 male and female rats, respectively, were treated dermally with test substance under occlusive conditions for 24 hours. Additionally, a control group consisting of 5 male and female rats, respectively, was treated in the same manner as dosed animals except that the test substance was omitted. Animals were subjected for mortality, general condition and clinical signs at 0.5, 1, 2, 4 and 6 hours after dosing on Day 0 and subsequently once daily for 14 days. Individual body weights were recorded prior to application of the test substance on Day 0 and on Days 3, 7 and 14 days after treatment. Macroscopic examination was performed in the end of the observation period at terminal sacrifice. There was no mortality and no effects on body weight gain during the 14-day observation period. No clinical abnormalities were evident in any animal throughout the study. Macroscopic postmortem examination did not reveal any abnormalities. The LD50 value for dermal toxicity was considered to be > 5000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Oral

The acute oral toxicity of the test substance was assessed in a study according to OECD Guideline 423 and in compliance with GLP (2015a). In a first step, a total dose of 2000 mg/kg bw of the test substance diluted in corn oil was administered to 3 female rats. Animals were observed 0.5, 1, 2, 4 and 6 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to dosing on Day 0 and on Days 1, 3, 7 and on the day of necropsy, Day 14. Macroscopic examination was performed at the end of the observation period at terminal sacrifice. In a second step, 3 additional female rats were treated with 2000 mg/kg bw of the test substance diluted in corn oil. No mortalities were observed at 2000 mg/kg bw until the end of the study. Abnormal gait was evident in 2 animals at 1 and 2 hours after dosing. The sign disappeared 4 hours after dosing. All animals showed expected gains in body weight over the study period and no abnormalities were noted at necropsy. Based on the results of this study, the LD50 value was determined to be > 2000 mg/kg bw in rats. In accordance with OECD Guideline 423, Annex 2d, a cut-off value of 5000 mg/kg bw was derived, since no mortality occurred at 2000 mg/kg bw.

 

Dermal

The acute dermal toxicity of the test substance was assessed in a study according to OECD Guideline 402 and in compliance with GLP (2015b). In a preliminary study, 1 male and female rat, respectively, were treated dermally with 5000 mg/kg bw test substance. Since no mortality was observed at 5000 mg/kg bw this dose level was selected for the main study. In the main study, 5 male and female rats, respectively, were treated dermally with test substance under occlusive conditions for 24 hours. Additionally, a control group consisting of 5 male and female rats, respectively, was treated in the same manner as dosed animals except that the test substance was omitted. Animals were subjected for mortality, general condition and clinical signs at 0.5, 1, 2, 4 and 6 hours after dosing on Day 0 and subsequently once daily for 14 days. Individual body weights were recorded prior to application of the test substance on Day 0 and on Days 3, 7 and 14 days after treatment. Macroscopic examination was performed in the end of the observation period at terminal sacrifice. There was no mortality and no effects on body weight gain during the 14-day observation period. No clinical abnormalities were evident in any animal throughout the study. Macroscopic postmortem examination did not reveal any abnormalities. The LD50 value for dermal toxicity was considered to be > 5000 mg/kg bw.


Justification for classification or non-classification

The available data on acute oral and dermal 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.