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Description of key information

The acute oral LD50 of the test item in Chinese hamsters of both sexes observed over a period of 14 days is greater than 6000 mg/kg. When applied dermally, the acute LD50 was greater than 2000 mg/kg as observed in rats.

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:
1979-10-05-1979-12-03
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
hamster, Chinese
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4-6 weeks old
- Weight at study initiation: 27-37g
- Housing: Individually in Macrolon cages
- Diet: NAFAG, Gossau SG, ad libitum
- Drinking water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2°C
- Humidity (%): 55 +/- 10 %
- Photoperiod: 10 hours light
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
DOSAGE PREPARATION: The test item was suspended to achieve the corresponding dosage level. Before treatment the suspension was homogeneously dispersed with an Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.
Volume: 10 and 20 mL/kg body weight
Doses:
3000, 4000, 5000, 6000 mg/kg bw
No. of animals per sex per dose:
5 male
5 female
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Bodyweight: Immediately prior to dosing and after 7 and 14 days.
Clinical observations: Daily
Preliminary study:
none
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 6 000 mg/kg bw
Based on:
test mat.
Mortality:
no mortality
Clinical signs:
Total recovery within 7-8 days
Sedation:
Slight effects, recovery after 2 days (3000 mg/kg)
Slight effects, recovery after 5 days (all other dose groups)
Dyspnoe:
Slight effects, recovery after 7 days (3000 mg/kg)
Slight effects, recovery after 6 days (all other doses)

Exophthalmos
slight effects, recovery after 5 hours (dose group 3000 mg/kg)
slight effects, recovery after 24 hours (dose group 4000 mg/kg)
slight effects, recovery after 2 days (dose group 5000 mg/kg)
slight effects, recovery after 3 days (dose group 6000 mg/kg)

Ruffled fur
Slight effects, recovery after 6 days (Dose group 3000 mg/kg)
Slight and moderate effects, recovery after 6 days (dose group 4000 mg/kg)
Slight and moderate effects, recovery after 5 days (dose group 5000 mg/kg)
Slight and moderate effects, recovery after 6 days (dose group 6000 mg/kg)

Body position (curved)
Slight effects, recovery after 2 days (4000 mg/kg)
Slight effects, recovery after 2 days (5000 mg/kg)
Slight effects, recovery after 2 days (6000 mg/kg)
Body weight:
Reduction of bodyweight in the dose group of 4000 mg/kg from 37 g to 34 g (males after 14 days) and from 30 g to 27 g (females after 14 days).
Reduction of bodyweight in the highest dose group of 6000 mg/kg from 30 to 28 g (females after 14 days).
Gross pathology:
No substance related gross organ changes were seen.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
6 000 mg/kg bw

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:
November 25, 2014 - December 18, 2014
Reliability:
1 (reliable without restriction)
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402.
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: Charles River Wiga GmbH, Germany
- Age at study initiation: male animals approx. 8 weeks, female animals approx. 12 weeks
- Weight at study initiation: mean weights males: 230 g; mean weights females: 209 g
- Fasting period before study: no
- Housing: Single housing in Makrolon cage, type III
- Diet: VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany
- Water: Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C
- Humidity (%): 30 – 70
- Air changes (per hr): Approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h
Type of coverage:
semiocclusive
Vehicle:
other: 0.5% solution of CMC (sodium carboxymethylcellulose) in deionized water
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:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing of the application site with warm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.00 g/kg bw
- Concentration: 40g/100ml (paste)
- Constant volume or concentration used: yes
- For solids, paste formed: yes
Duration of exposure:
24h
Doses:
2000 mg/kg body weight
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.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality occurred
Clinical signs:
No systemic clinical signs were observed during clinical examination. Due to the yellowish discoloration of the application area no local findings such as erythema could be determined in all animals on study day 1. Thereafter, no erythema or edema were observed, however slight yellowish discoloration of the application area was still present in all animals until study day 3.
Body weight:
The mean body weight of all animals increased within the normal range throughout the study period with one exception in the female group. The body weight increased in this animal within the normal range during the first week, but stagnated during the second week. As this female did not show any symptoms or change in behavior, the observed 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
Conclusions:
Under the conditions of this study the median lethal dose (LD50) of the test substance after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.
Executive summary:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females)were dermally exposed to a single dose of 2000 mg/kg bw of test material (as a suspension in 0.5 % CMC-solution) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred signs of systemic toxicity were observed. Due to the yellowish discoloration of the application area no erythema could be determined on study day 1 only. Slight yellowish discoloration of the application area was observed on the first three days after application. The mean body weight of all animals increased within the normal range throughout the study period with one exception in the female group. The body weight increased in this animal within the normal range during the first week, but stagnated during the second week. As this female did not show any symptoms or change in behavior, the observed stagnation is considered to be unspecific. No macroscopic pathologic abnormalities were noted in all animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

The study was performed to assess the range of mortality following oral administration of the test material. The study procedure was equivalent to OECD Guideline 401. The following nominal concentrations were tested: 3000, 4000, 5000 and 6000 mg/kg bw. The acute oral LD50 of the test item in Chinese hamsters of both sexes observed over a period of 14 days is greater than 6000 mg/kg. Clinical symptoms observed were dyspnoea, sedation, ruffled fur and curved body position, being common symptoms in acute tests. The animals recovered within 8 days. In conclusion, the test material has practically no acute toxicity to the hamster by this route of administration.

Acute dermal toxicity

In a GLP-compliant acute dermal toxicity study (Limit Test) according to OECD guideline 402, young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of test material (as a suspension in 0.5 % CMC-solution) to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred signs of systemic toxicity were observed. Due to the yellowish discoloration of the application area no erythema could be determined on study day 1 only. Slight yellowish discoloration of the application area was observed on the first three days after application. The mean body weight of all animals increased within the normal range throughout the study period with one exception in the female group. The body weight increased in this animal within the normal range during the first week, but stagnated during the second week. As this female did not show any symptoms or change in behavior, the observed stagnation is considered to be unspecific. No macroscopic pathologic abnormalities were noted in all animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 2000 mg/kg body weight.

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 1272/2008 (CLP). As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008.