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Administrative data

Description of key information

Oral: OECD 425; rat LD50 >5000 mg/kg. Reliability = 1

Inhalation: No study available
Dermal: OECD 402; rat LC50 >5000 mg/kg. Reliability = 1

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:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: U.S. FDA, Redbook 2000: IV.C.2: Acute Oral Toxicity Tests (1993)
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately 10 weeks old
- Weight at study initiation: ranged from approximately 209.5 to 233.4 g
- Fasting period before study: yes
- Housing: housed individually in solid-bottom caging with bedding and appropriate species-specific enrichment
- Diet: PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002, ad libitum
- Water: ad libitum
- Acclimation period: 6-day quarantine period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-26ºC
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): approximate 12-hour light/dark cycle
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- A single oral dose of the test item was suspended in deionized water and adjusted for purity.
Doses:
5000 mg/kg
No. of animals per sex per dose:
5 rats at 5000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: observed for clinical signs at the beginning of fasting, just before dosing (test day 1), once during the first 30 minutes after dosing and 2 more times on the day of dosing, and once each day thereafter. Clinical observations were inadvertently not recorded on test day 5.
-Frequency of weighing: test days -1, 1, 8, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: no
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
highest dose tested
Mortality:
No deaths occurred.
Clinical signs:
No clinical abnormalities were observed.
Body weight:
No overall bodyweight losses were observed.
Gross pathology:
No gross lesions were present in the rats at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 is greater than 5000 mg/kg.
This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
Executive summary:

The test item was administered by oral gavage to five fasted female rats at a dose level of 5000 mg/kg. All rats were observed for mortality, body weight effects, and clinical signs for 14 days after dosing. The rats were necropsied to detect grossly observable evidence of organ or tissue damage.

No incidents of mortality, overall bodyweight losses or clinical abnormalities were observed. No gross lesions were present in the rats at necropsy. Under the conditions of this study, the oral LD50 for the test substance was greater than 5000 mg/kg for female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
GLP, guideline study

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
other justification
Justification for data waiving:
other:
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:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: MAFF Japan Test Guidelines for Agricultural Chemicals 12-Nousan-8147 (2000)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: approximately 9 weeks
- Weight at study initiation: Mean rat weight: Male - 296.1 g; Female - 219.1 g
- Fasting period before study: not reported
- Housing: housed individually in solid-bottom caging with bedding and appropriate species-specific enrichment
- Diet: PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6-day quarantine period


ENVIRONMENTAL CONDITIONS
- Temperature: 20-26ºC
- Humidity: 30-70%
- Photoperiod: approximate 12-hour light/dark cycle
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: The paste was spread evenly, directly on the skin, covering an area of approximately 37 square centimetres.
- % coverage: Thirty-seven square centimeters is equal to approximately 10 percent of the total body surface area of rats in the 200 - 300 g body weight range.
- Type of wrap if used: The test substance was covered with a 2-ply gauze patch. The rats were then wrapped with stretch gauze bandage and self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: Approximately 24 hours after treatment,

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The test substance was measured for each animal on the day of treatment at a dose of 5000 mg/kg of body weight. The amount of test substance designated for each animal was calculated based on body weights collected prior to treatment.
- For solids, paste formed: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): The aliquot of test substance designated for an animal was moistened with approximately 1 mL of deionized water to form a thick paste.
Duration of exposure:
Approximately 24 hours
Doses:
1
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations: Daily animal health observations were conducted throughout the study for mortality and signs of illness, injury, and abnormal behaviour. The rats were weighed on test days 1, 8, and 15, and were observed daily for clinical signs of toxicity and dermal irritation (weekends and holidays excluded for dermal irritation)
- Other examinations performed: All rats were euthanized at the end of the 15-day test period and examined to detect grossly observable evidence of organ or tissue damage.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other:
Remarks:
highest dose tested
Mortality:
There were no instances of mortality at 5000 mg/kg.
Clinical signs:
One male exhibited scabbing on the right shoulder, between test days 12-15. No other clinical abnormalities were observed.

At the beginning of the observation period (approximately 24 hours after exposure), on test day 2, erythema was observed in 3/5 male animals, with a score of 1. All erythema was resolved by test day 3. There were no instances of edema observed.
Body weight:
There were no overall body weight losses
Gross pathology:
No gross lesions were present in the rats at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
LD50 > 5000 mg/kg
Executive summary:

A single dose of the test item was applied to the shaved, intact skin of 5 male and 5 female rats at a dose level of 5000 mg/kg of body weight. The application site was covered with a semi-occlusive dressing for 24 hours, after which the test substance was removed. The rats were observed for 14 days following application. The rats were necropsied to detect grossly observable evidence of organ or tissue damage at the end of the 15-day test period.

There were no incidents of mortality and no overall body weight losses. One male exhibited scabbing on the right shoulder, between test days 12-15. No other clinical abnormalities were observed. At the beginning of the observation period (approximately 24 hours after exposure), on test day 2, erythema was observed in 3/5 male animals, with a score of 1. All erythema was resolved by test day 3. There were no instances of edema observed. No gross lesions were present in the rats at necropsy.

Under the conditions of this study, the dermal LD50 for the test item was greater than 5000 mg/kg of body weight when applied to the skin of male and female rats for 24 hours.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
GLP, guideline study

Additional information

In an OECD 425 guideline study conducted under GLP conditions, five female rats were given the test substance via gavage at doses of 5000 mg/kg. No mortality or significant clinical signs were observed during the exposure or the 14-day post-exposure observation period. There were no remarkable changes in body weight. No gross lesions were present in the rats at necropsy. Under the conditions of this study, the oral LD50 in rats was greater than 5000 mg/kg.

In an OECD 402 guideline study conducted under GLP conditions, 5 male and 5 female rats per dose were given the test substance via semi-occlusive dermal administration at a dose of 5000 mg/kg. No mortality or significant clinical signs were observed during the exposure or the 14-day post-exposure observation period. There were no remarkable changes in body weight and no gross lesions were present in the rats at necropsy. Under the conditions of this study, the dermal LD50 in rats was greater than 5000 mg/kg.


Justification for classification or non-classification

Based on the oral and dermal LD50 values in rats of >5000 mg/kg, no classification is required for acute oral or dermal endpoints according to the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

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