Registration Dossier

Administrative data

Description of key information

oral: The acute oral LD50 of the test substance was determined to be 4520 mg/kg bw.

dermal: The acute dermal median lethal dose (LD50) was determined to be > 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: according to BASF-internal standard
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 78/574

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: males: 210 g - 270 g, females: 150 g - 210 g
- Diet: The animals were offered a standardized animal laboratory diet (Harilan, MRH, H. Egersmann KG, Germany)
- Fasting period: 15 - 20 h before administration.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 21.5, 31.6, 38.3, 50, 68.1% (G/V)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
2150, 3160, 3830, 5000, 6810 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations. at 1 h and days 1, 2, 7, 14 after application, weighing: prior to administration, days 2 - 4, day 7, days 12 - 13
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (dyspnoe, apathy, abnormal position, staggering, spastic gait, ruffled fur, diarrhea, cyanosis, paresis, poor general condition)
Statistics:
no
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 520 mg/kg bw
Based on:
test mat.
Mortality:
Male animals:
2150 and 3160 mg/kg: no deaths after 14 days;
3830 mg/kg: 2/5 after 14 days;
5000 mg/kg: 4/5 after 14 days;
6810 mg/kg: 5/5 after 14 days
Female animals:
2150 mg/kg: no deaths after 14 days;
3160 mg/kg: 1/5 after 14 days;
3830 mg/kg: 0/5 after 14 days;
5000 mg/kg: 2/5 after 14 days;
6810 mg/kg: 5/5 after 14 days
Clinical signs:
Dyspnea, apathy, abnormal position, staggering, spastic gait, ruffled fur, diarrhea, cyanosis, paresis, poor general state
Body weight:
Mean body weight male animals: 260 g - 270 g at study start, 309 g after 13 days
Mean body weight female animals: 150 g - 210 g at study start, 223 g after 13 days
Gross pathology:
Animals that died: heart: acute dilatation (right); acute congestive hyperemia; stomach: atonic, dilated, liquid content, mucosa diffuse reddened; intestine: atonic, diarrheic content, reddened mucosa; urine: orange-coloured up to red staining.
Sacrificed animals: nothing abnormal detected.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 520 mg/kg bw
Quality of whole database:
similar OECD TG 401

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
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:
July 7, 2016 - July 29, 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
February 24, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nousan No. 8147
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bioassay Labor für biologische Analytik GmbH, 69120 Heidelberg, Germany
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Do_0164
- Expiration date of the lot/batch: May 30, 2019

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, under argon
- Stability under test conditions: guaranteed

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation:
- Fasting period before study:
- Housing: single housing, Makrolon cage, type III
- Bedding: H 15005-29; Ssniff, Spezialdiäten GmbH (Experimental Animal Diets Inc., 59494 Soest, Germany)
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 – 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
deionized
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal and dorsolateral parts of the trunk
- % coverage: about 40 cm² (corresponds to at least 10% of the body surface)
- Type of wrap if used: 4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing: rinsing of the application site with warm water

TEST MATERIAL
- Amount(s) applied: 5 mL/kg bw
- Constant volume or concentration used: yes, 40 g/100mL
- For solids, paste formed: no

Duration of exposure:
14 days
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Individual body weights shortly before application (day 0), weekly thereafter and on the last day of observation. Clinical signs for each animal were recorded several times on the day of application and at least once during each workday thereafter. A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes
- Other examinations performed:
Scoring of skin findings:
Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.

The evaluation of skin reactions was performed according to Draize, J. H. "Dermal toxicity."
Erythema and eschar formation
Grading
0 No erythema
1 Very slight erythema (barely perceptible)
2 Well- defined erythema
3 Moderate to severe erythema
4 Severe erythema (beet redness) to eschar formation preventing grading of erythema

Edema formation
Grading
0 No edema
1 Very slight edema (barely perceptible)
2 Slight edema (edges of area well- defined by definite raising)
3 Moderate edema (raised approx. 1 mm)
4 Severe edema (raised more than 1 mm and extending beyond area of exposure)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No systemic clinical signs were observed during clinical examination. No local effects were observed.
Body weight:
The body weight of the male animals increased within the normal range throughout the study period. The body weight of the female animals increased within the normal range throughout the study period with one exception. In one female animal the body weight stagnated during the first week, but the animal gained weight in a normal range during the second week. Due to the fact that stagnation or slight loss of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
OECD TG 402

Additional information

Oral

An acute oral toxicity test was conducted according to BASF internal standards similar to OECD Guideline 401. The test substance was administered to 5 rats per sex at the dose levels of 2150, 3160, 3830, 5000, 6810 mg/kg bw. The animals were observed for a period of 14 days. No mortality was observed in the 2150 mg/kg bw dose group after 14 days observation period. All animals died at the highest dose group of 6810 mg/kg bw. The following clinical signs were observed: dyspnea, apathy, abnormal position, staggering, spastic gait, ruffled fur, diarrhea, cyanosis, paresis and poor general state. The animals that died showed acute heart dilation; acute congestive hyperemia; atonic, dilated stomach with liquid content and diffuse reddened mucosa. The intestine was atonic with diarrhea content and reddened mucosa. The urine was orange-coloured up to red staining. No abnormal findings were detected in the sacrificed animals. The LD50 was determined to be 4520 mg/kg bw (BASF SE 1980).

Dermal

In an acute dermal toxicity study (Limit Test) according OECD TG 402, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test item, concentrated(as suspension in deionized water). The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days.

No mortality occurred. Neither signs of systemic toxicity nor local skin effects were observed. The body weight of the male animals increased within the normal range throughout the study period. The body weight of the female animals increased within the normal range throughout the study period with one exception. In one female animal the body weight stagnated during the first week, but the animal gained weight in a normal range during the second week. Due to the fact that stagnation or slight loss of body weight is commonly known for females after dermal applications, this stagnation is considered to be unspecific. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg bw (BASF SE, 2017).

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.