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Administrative data

Description of key information

Oral: LD50 >2000 mg/kg bw, rat, Zelenák 2014
Dermal: LD50 >2000 mg/kg bw, rat, Matting 2015

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:
2013-10-22 until 2013-11-14
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was carried out following OECD guideline 425 and in compliance with GLP. The method description is well documented.
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: S.Pietro al Natisone (UD), Zona Industriale Azzida, 57, 33040, Italy
- Strain: RccHan:WIST
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 184-193 g
- Fasting period before study: Yes (overnight)
- Housing: Individually in Type II. polypropylene/polycarbonate cages
- Diet: Ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" ad libitum (except for overnight pre-dose fast and for 3 hours post dose) - Ssniff Spezialdiäten GmbH, D-59494 Soest Germany
- Water: Municipal tap water ad libitum
- Acclimation period: At least 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22 October 2013 To: 14 November 2013
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5% CMC in distilled water
Details on oral exposure:
DOSE VOLUME: 10 mL/kg body weight

Doses:
2000 and 550 mg/kg bw
No. of animals per sex per dose:
1 female at 550 mg/kg bw, 3 females at 2000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed individually after dosing at 30 minutes, 1, 2, 3, 4, and 6 hours and once each day for 14 days thereafter. Body weights were recorded on Days -1 (prior to the removal of food), 0 (prior to administration), 7 and 14.
- Necropsy of survivors performed: Yes
Statistics:
Data was evaluated using the Acute Oral Toxicity (OECD Test Guidelines 425) Statistical Programme (AOT 425 Stat Pgm).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities
Clinical signs:
There were no treatment-related clinical signs.
Body weight:
There were no treatment related body weight changes.
Gross pathology:
There was no treatment related macroscopic findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, the acute oral median lethal dose LD50 of the test item was greater than 2000 mg/kg bw in RccHan:WIST female rats.
Executive summary:

An acute oral toxicity (up and down procedure) study was conducted with 4 animals (female RccHan:WIST rats). Animals were treated with a single oral (gavage) dose of the test item at a dose level of 550 (1 animal) or 2000 (3 animals) mg/kg body weight (bw) followed by a 14 day observation period. The animals were fasted overnight prior to treatment and food was returned 3 hours after dosing. All animals were observed individually after dosing at 30 minutes, 1, 2, 3, 4 and 6 hours post treatment and once each day for 14 days thereafter. Body weight was measured on Day -1 (prior to removal of food), Day 0 (prior to administration) and weekly thereafter. All animals were examined macroscopically at the end of the study.

No deaths occurred during the study. Treatment with at 550 or 2000 mg/kg bw did not cause any test item related adverse effects during the 14 days observation period. There was no evidence of the macroscopic observations in animals terminated on Day 14. There were no treatment related changes in the body weights. The body weights of the animals were within the range commonly recorded for this strain and age.

Under the conditions of this study, the acute oral median lethal dose LD50 of the test item was greater than 2000 mg/kg bw in RccHan:WIST 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
Study period:
2013-10-22 until 2013-11-05
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, no restrictions, fully adequate for assessment.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
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: Harlan Laboratories S.r.l., S.Pietro al Natisone (UD), Zona Industriale Azzida, 57, 33040, Italy.
- Strain: RccHan:WIST
- Age at study initiation: Young adult.
- Weight at study initiation: 214-243 g.
- Fasting period before study: None.
- Housing: Individually in Type II polypropylene/polycarbonate cages.
- Diet: ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" ad libitum. Ssniff Spezialdiäten GmbH, D-59494, Soest, Germany.
- Water: Municipal tap water ad libitum.
- Acclimation period: 6 Days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22 October 2013 To: 05 November 2013
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Back (shaved approximately 24 hours before treatment)
- % coverage: Approximately 10%
- Type of wrap if used: Sterile gauze pads kept in contact with the skin by using a patch of adhesive hypoallergenic plaster. The entire trunk of the animal was then wrapped with semi occlusive plastic wrap.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes (body temperature water).
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: Yes (appropriate amount of test item moistened with water and distributed as uniformly as possible onto the skin).

Duration of exposure:
24 hours
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: Observed on the day of treatment, at 1 and 5 hours after the application of the test item, and once each day for 14 days thereafter. Body weights recorded on Day 0 (before treatment) and on Days 7 and 14.
- Necropsy of survivors performed: Yes
Statistics:
Not applicable (limit test, no mortality).
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities.
Clinical signs:
There were no treatment related clinical signs or skin irritation.
Body weight:
There were no treatment related effects on body weight.
Gross pathology:
There were no treatment related macroscopic findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute median lethal dose (LD50) of the test item after single dermal administration was greater than 2000 mg/kg bw in male and female RccHan:WIST rats.
Executive summary:

A single administration of the test item at a dose of 2000 mg/kg body weight (bw) was applied dermally to 5 male and 5 female RccHan:WIST rats, followed by a 14-day observation period. The test item was applied as supplied. The application period was 24 hours. Clinical observations along with a check of viability and mortality were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured prior to dosing on Day 0 and on Days 7 and 14. Rats were killed and subjected to a gross macroscopic examination at the end of the 2-week observation period (Day 14).

No mortality occurred during the 14-day observation period after a 24-hour dermal exposure test item to RccHan:WIST rats. No adverse clinical signs were observed after treatment with the test item or during the 14 day observation period. There were no treatment related effects on body weight or body weight gain during the observation period. There was no evidence of any treatment-related macroscopic findings at a dose level of of 2000 mg/kg bw at necropsy.

The acute median lethal dose (LD50) after a single dermal administration was greater than 2000 mg/kg bw in male and female RccHan:WIST rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Oral acute toxicity

Zelenák (2014) conducted a study in compliance with GLP and according to OECD guideline. The animals were treated with a single oral (gavage) dose of the test item at a dose level of 550 (1 animal) or 2000 (3 animals) mg/kg body weight (bw) followed by a 14 day observation period. No deaths occurred during the study and the treatment did not cause any substance related adverse effects during the observation period.

The study is considered complete, reliable and adequate. The acute oral toxicity value LD50 > 2000 mg/kg bw is carried forward for the purposes of risk assessment, and classification.

Dermal acute toxicity

Matting (2015) performed a limit test study carried out in compliance with GLP and according to OECD guideline. The animals were exposed 24 hours to the substance, after which they were kept in observation for 14 days. There were no adverse clinical signs noted in any animals throughout the study. Thus, the median lethal dose of the test item after single dermal administration was found to be greater than 2000 mg/kg bw.

The study is considered complete, reliable and adequate. The acute dermal toxicity value LD50 > 2000 mg/kg bw is carried forward for the purposes of risk assessment, and classification.

Justification for selection of acute toxicity – oral endpoint
Only one study was available, which was carried out according to guideline and under GLP.

Justification for selection of acute toxicity – dermal endpoint
Only one study was available, which was carried out according to guideline and under GLP.

Justification for classification or non-classification

Acute oral toxicity

The key value selected for the acute oral toxicity is LD50 > 2000 mg/kg bw. According to Regulation (EC) No. 1272/2008, Annex I, Part 3, Table 3.1.1., the substance in not classified as acutely toxic.

Acute dermal toxicity

The key value selected for the acute dermal toxicity isLD50 > 2000 mg/kg bw. The substance does not meet the criteria for classification and labelling for acute dermal toxicity as set out in Regulation (EC) No. 1272/2008, Annex I, Part 3, Table 3.1.1.