Registration Dossier

Administrative data

Description of key information

A single dose of 2000 mg/kg bw of the test substance was administrated oral to groups of male and female rats (5/sex, OECD guideline 401). A limit dose of 1333 mg/kg bw (high siziness when mixed with vehicle) was applied dermally to groups of male and female rats (5/sex, OECD guideline 402). Application of the test substance did not induce any signs of toxicity. None of the animals died, viability and bodyweight gain were unaffected by the test article. Gross necropsy did not reveal any treatment related abnormalities. LD50 after single oral administration is > 2000 mg/kg bw, LD50 acute dermal > 1333 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
Study period:
1992-06-24 - 1992-08-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: albino rats (Tif: RAI f (SPF))
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, Stein, Switzerland
- Weight at study initiation: 181 - 210 g
- Housing: Group-housed in Macrolon cages type 4 with standardized soft wood bedding; animals were identified with numbers from 1 to 5 using picric acid stain on the fur
- Diet: Standard diet, ad libitum
- Water: Fresh water, ad libitum
- Acclimation period: At least for 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 2 °C
- Humidity: 55 +/- 10 %
- Air conditioning: 15 air changes per hour
- Photoperiod: 12 hour/day light cycle

IN-LIFE DATES: From: 1992-07-14/1992-07-27 To: 1992-07-28/1992-08-10
Route of administration:
oral: gavage
Vehicle:
other: 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80
Details on oral exposure:
VOLUME APPLIED: 20 mL/kg bw
Doses:
2000 mg/kg bw (males and females)
No. of animals per sex per dose:
5 rats
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Observations and records:
Mortality: daily
Signs and symptoms: daily
Body Weight: immediately before application and on days 7 and 14
- Necropsy of survivors performed: yes
Statistics:
Body weight: Group means and standard deviations
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
The following death rate was observed: 0 % at 2000 mg/kg.
Clinical signs:
Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute tests. Additionally, reduced locomotor activity was observed in all animals. The animals recovered within 6 to 7 days.
Body weight:
The body weight gain of the animals was not affected.
Gross pathology:
A spotted thymus was found in one female. No deviations from normal morphology were found in the remaining animals.

Based on the observations, oral LD50 value was to be greater than 2000 mg/kg bw.

Interpretation of results:
GHS criteria not met
Executive summary:

In an acute oral toxicity study groups of male and female rats (5/sex) were given a single oral gavage dose of the test item (as described in section 1.2) in a standard vehicle at a limit dose of 2000 mg/kg bw and observed for 14 days. No mortality occurred. Piloerection, hunched posture, and dyspnea were seen, being common symptoms in acute tests. Additionally, reduced locomotor activity was observed in all animals. The animals recovered within 6 to 7 days. The body weight gain of the animals was not affected. A spotted thymus was found in one female. No deviations from normal morphology were found in the remaining animals. Based on these observations, the oral LD50 value of the test item was greater than 2000 mg/kg bw.
Oral LD50: > 2000 mg/kg bw (per sex and combined)

This study is classified as acceptable. It satisfies the guideline requirement for an acute oral toxicity study according to OECD 401.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 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:
1992-06-24 - 1992-08-31
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
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
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: albino rats (Tif: RAI f (SPF))
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, Stein, Switzerland
- Weight at study initiation: 216 - 290 g
- Housing: Individually in Macrolon cages type 3 with standardized soft wood bedding
- Diet: Standard diet, ad libitum
- Water: Fresh water, ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 +/- 2 °C
- Humidity: 55 +/- 10 %
- Photoperiod: 12 hour/day light cycle

IN-LIFE DATES: From: 1992-07-14/1992-07-23 To: 1992-07-28/1992-08-06
Type of coverage:
semiocclusive
Vehicle:
other: 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80
Details on dermal exposure:
TEST SITE
- Pretreatment: Area of exposure was shaved 24 hours before application
- Area of exposure: backs of the animals
- % coverage: 10
- Type of wrap: On test day 1 the test item was evenly dispersed on the skin and was covered with a gauze-lined semiocclusive dressing fastened around the trunk with an adhesive elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was cleaned with lukewarm tap water and the skin reaction was appraised.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Because of the high viscosity of the test item mixture, only 1333 mg/kg bw could be applied, respecting the maximal application volume of 4 mL/kg bw.

VEHICLE
- 0.5 % (w/v) carboxymethylcellulose in 0.1 % (w/v) aqueous polysorbate 80
Duration of exposure:
24 hours
Doses:
1333 mg/kg bw
No. of animals per sex per dose:
5 rats
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Observations and records:
Mortality: daily
Signs and symptoms: daily
Body Weight: immediately before application and on days 7 and 14
- Necropsy of survivors performed: yes
Statistics:
Body weight: Mean and SD
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 333 mg/kg bw
Based on:
test mat.
Mortality:
The following death rate was observed: 0 % at 1333 mg/kg bw.
Clinical signs:
The following clinical signs were observed: Piloerection and hunched posture were seen, being common symptoms in acute dermal tests. The animals recovered within 2 days.
Body weight:
The body weight gain of the animals was not affected throughout the study.
Gross pathology:
At necropsy, a spotted thymus was found in two males. No deviations from normal morphology were found in the remaining animals.

Based on the observations, the dermal LD50 value was to be greater than 1333 mg/kg bw.

Because of the high viscosity of the test item mixture, only 1333 mg/kg bw could be applied, respecting the maximal application volume of 4 mL/kg bw.

Interpretation of results:
GHS criteria not met
Executive summary:

In an acute dermal toxicity study groups of male and female rats (5/sex) were dermally exposed to the test item (as described in section 1.2) in a standard vehicle for 24 hours to at least 10% of body surface area at a limit dose of 1333 mg/kg bw. Animals then were observed for 14 days. Clinical signs consisted of transient piloerection and hunched posture regarded as common symptoms in acute testing. No mortality occurred in this study. At necropsy, no observable abnormalities were noticed in eight animals and a spotted thymus was found in two males. Based on these observations, the dermal LD50 value of the test item was greater than 1333 mg/kg bw.
Dermal LD50: > 1333 mg/kg bw (per sex and combined)

This study is classified as acceptable. It satisfies the guideline requirement for an acute dermal toxicity study according to OECD 402.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
1 333 mg/kg bw

Additional information

Procedure and observations

To evaluate the acute oral toxicity, a single dose (2000 mg/kg bw) of the test article was administrated to a group of 5 male and 5 female rats by oral gavage (Ciba-Geigy 1992a). Following dosing, the animals were observed for 14d. Examination of clinical signs and viability were performed daily, weighing once a week.

There were no deaths as a result of treatment with the test article. Clinical signs of toxicity or changes in body weight gain were not observed during the observation period. Reduced locomotor activity was observed in all animals. The animals recovered within 6 to 7 days. A spotted thymus was found in one female. No deviations from normal morphology were found in the remaining animals.

 

Dermal toxicity of the test substance was evaluated on a group of five male and 5 female rats which were treated with the test article at a single dose of 1333 mg/kg (highest applicable dose due to high viscosity) by dermal application (Ciba 1992b). The animals were examined daily for clinical signs, body weight gain and viability. All animals were necropsied and examined macroscopically.

No deaths occurred during the study period. Neither clinical signs of systemic toxicity nor local effects of the test article on the skin at the application site were observed during the observation period. At necropsy, no observable abnormalities were noticed in eight animals and a spotted thymus was found in two males.

Discussion

Application of the test substance via oral or dermal route did not induce any signs of toxicity. None of the animals died, viability and bodyweight gain were unaffected by the test article. A spotted thymus was found in one female after oral administration and in two males after dermal treatment. These findings are considered as individual variations and not as treatment related effects. Reduced locomotor activity after oral administration is considered to be a common symptom in acute toxicity studies. LD50 after single oral administration is > 2000 mg/kg bw, LD50 after single dermal application is > 1333 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
Only study available, study valid without restriction.

Justification for selection of acute toxicity – dermal endpoint
Only study available, study valid without restriction.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute toxicity under Directive 67/548/EEC, as amended for the 30th time in Directive 2008/58/EC.

                               

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. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No. 1272/2008, as amended for the fifth time in Directive EC 944/2013.