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Description of key information

OECD guideline, GLP-compliant studies were available for acute oral toxicity and acute dermal toxicity. In both studies the LD50 values exceed the limit dose of 2000mg/kg.

It is not appropriate to include an LD50 value for the chemical safety assessment above as this is determined to be greater than the highest concentration tested.

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:
equivalent or similar to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
March 22, 1996
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
February 24, 1987
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Dated 31 July 1992
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Supplier: Charles River Wiga, Germany
Age: 5-6 weeks old upon arrival
identification: earmarked
Caging: five animals per cage (stainless stell cages, fitted with wire-screen floor and front)
Acclimatization: 9 or 13 days
Lighting: 12 hours light/dark cycle
Temperature: 22 +/- 3C
Ventilation: ca. 10 air changes/hr
Diet: standard chow ad libitum
Water: tap water ad libitum
Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
Animals were dosed with a dosing volume of 10 ml/kg bw of a 200 mg/ml suspension of test material in maize oil to obtain the 2000 mg/kg dose level. The exact amount of the test substance to be dosed was calculated for each animal and administered by means of a syringe, by oral gavage. Animals fasted overnight prior to dosing and 4 hours after.
Doses:
2000 mg/kg limit dose
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
Animals were observed for mortality 14 days post exposure.
Body weights of each animal were recorded immediately before dosing on day 0 and in the surviving animals on days 3, 7 and 14 of the study.
Animals were sacrificed on day 14 with CO2 and subjected to gross pathology.
Preliminary study:
No mortality observed in 2 males.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female was found dead on day 3
Clinical signs:
blepharospasm in two males was observed
prior to death, the female showed sluggishness, blepharospasm, dyspnoea and coma
Body weight:
All surving animals gained weight during the study
Gross pathology:
No treatment related gross alterations was observed
Interpretation of results:
GHS criteria not met
Conclusions:
Since only one animal died during the 14 -day observation period, the oral LD50 of the test material is considered to exceed 2000 mg/kg body weight, in both male and female rats.
Endpoint conclusion
Endpoint conclusion:
no 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
EEC Directive 92/69/EEC, dated 31 July 1992
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Febraury 24, 1992
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 5-6 weeks
- Weight at study initiation: mean 201
- Housing: stainless steel cages, fitted with wire-screen floor and front
- Diet (e.g. ad libitum): standard rodent diet, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 50-70%
- Air changes (per hr): ca. 10 air changes/hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 15 January 1997 To: 4 February 1997
Type of coverage:
occlusive
Vehicle:
maize oil
Details on dermal exposure:
TEST SITE
- Area of exposure: 4 x 5 cm
- % coverage: at least 10% of total body surface
- Type of wrap if used: plastic foil, adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, residues removed with water
- Time after start of exposure: ca. 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5ml/kg

VEHICLE
- Maize oil
Duration of exposure:
24 h
Doses:
2000 mg/kg
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: Day 0, 3, 7, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology
Statistics:
Skin reactions were evaluated by the method of Draize et al (J. Pharamcol. Exp Ther. 82 (1944) 377-390)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
No treatment related effects were observed.


All animals gained weight during the 14-day observation
period. Some animals showed a slight dip in body weight on
postdosing day 3.
Body weight:
Apart from a slight dip in body weight in some animals, all animals gained weight during the 14-day study period
Gross pathology:
Effects on organs:
No gross abnormalities were observed.
Other findings:
Signs of toxicity (local):
Males: slight erythema.

Females: slight to moderate erythema, slight or moderate
encrustations and very slight or slight oedema during the
first week after exposure.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study, the LD50 value was determined to be >2000 mg/kg for the test substance
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

It is not appropriate to include a oral and/or dermal LD50 value for the chemical safety assessment above as this was determined to be greater than the highest concentration tested on both studies.

Justification for classification or non-classification

The LD50 value in the acute oral and dermal studies was >2000 mg/kg and therefore warrants no classifications for these endpoints under the CLP regulation (1272/2008 EC, as amended). No study available to assess inhalation toxicity and therefore not classified based on "data lacking" for this endpoint.