Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral

In an acute oral toxicity study in rats according to OECD guideline 401 an LD50 of above 5000 mg/kg bw was determined.

Dermal

In an acute dermal toxicity study in rats according to OECD guideline 403 an LD50 of above 2000 mg/kg bw was determined.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Remarks:
CD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4 - 6 weeks
- Weight at study initiation: 105 - 128 g
- Diet: ad libitum
- Water: ad libitum

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
1 % aqueous methylcellulose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25 % (w/v)
- Amount of vehicle: 20 mL/kg

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

Doses:
5000 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: twice daily
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths following a single oral dose of the test substance at 5000 mg/kg bw.
Clinical signs:
other: No clinical signs were observed up to the highest tested concentration.
Gross pathology:
Terminal autopsy findings were normal.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute LD50 oral to rats of the test substance was found to be greater than 5000 mg/kg bw.
Executive summary:

In an acute oral toxicity study according to OECD guideline 401, groups of fasted Sprague Dawley rats (5/sex) were given a single oral dose of the test substance in water at a limit dose of 5000 mg/kg bw. Animals were treated by gavage and were then observed for 14 days.

No mortality or clinical signs were observed. All rats achieved anticipated bodyweight gains throughout the study. No abnormal findings were observed during necropsy.

An LD50 of above 5000 mg/kg bw was determined for male and female animals.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw
Quality of whole database:
GLP and guideline compliant study

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
Exposure to the test substance by inhalation is unlikely, as physico-chemical properties suggest no evidence of a significant absorption by inhalation. The substance is practically non-volatile, with vapour pressure determined as below 2.6E-04 Pa at 25 °C (please refer to IUCLID section 4.6). Further, from experience in use formation of inhalable particles is not very likely. Thus, short-term inhalation toxicity testing of the test substance is not scientifically justified.
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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Remarks:
Crl;CD(SD)BR]
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7 - 10 weeks
- Weight at study initiation: 205 - 231 g
- Housing: individually in metal cages
- Diet: Standard laboratory rodent diet (Labsure LAD 1), ad libitum
- Water: ad libitum
- Acclimation period: at least 16 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 - 22
- Humidity (%): mean 46
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 50 x 50 mm
- % coverage: ~10
- Type of wrap: gauze which was held in place with an impermeable dressing.

REMOVAL OF TEST SUBSTANCE
- Washing: with warm (30 - 40 ºC) water and blotting dry with absorbent paper
- Time after start of exposure: 24 h


Duration of exposure:
24 h
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: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed once in the morning and again at the end of the experimental day. Clinical signs were recorded at each observation including the nature, severity , approximate time of onset and duration of each toxic sign. Individual bodyweights of rats on Days 1 (day of dosing), 8 and 15.
- Necropsy of survivors performed: Yes, all animals on the study were sacrificed on Day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination, which consisted of opening the abdominal and thoracic cavity. The macroscopic appearance of abnormal organs when present was recorded.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred at the 2000 mg/kg dose level.
Clinical signs:
other: There were no clinical signs observed. Furthermore, application of the test substance caused no irritation reactions or other dermal changes at the treatment sites.
Gross pathology:
No macroscopic abnormalities were found during necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute LD50 value for rats was found to be greater than 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study according to OECD guideline 403 (Huntingdon, 1988), groups of young (7 - 10 weeks) Sprague Dawley rats (5/sex)were dermally exposed to the test substance for 24 hours to 10 % of body surface area at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days.

No mortality or clinical signs were observed. Application of the test substance did not cause any irritation reactions or other dermal changes at the treatment site. Body weight gain was normal throughout the study period. No macroscopic abnormalities were found during necropsy.

An LD50 of above 2000 mg/kg bw was determined for male and female rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute oral toxicity

In an acute oral toxicity study according to OECD guideline 401 (Huntingdon, 1988), groups of fasted Sprague Dawley rats (5/sex) were given a single oral dose of the test substance in water at a limit dose of 5000 mg/kg bw. Animals were treated by gavage and were then observed for 14 days.

No mortality or clinical signs were observed. All rats achieved anticipated bodyweight gains throughout the study. No abnormal findings were observed during necropsy.

An LD50 of above 5000 mg/kg bw was determined for male and female animals.

Acute dermal toxicity

In an acute dermal toxicity study according to OECD guideline 403 (Huntingdon, 1988), groups of young (7-10 weeks) Sprague Dawley rats (5/sex) were dermally exposed to the test substance for 24 hours to 10 % of body surface area at a limit dose of 2000 mg/kg bw. Animals then were observed for 14 days.

No mortality or clinical signs were observed. Application of the test substance did not cause any signs of irritation or other dermal changes at the treatment site. Body weight gain was normal throughout the study period. No macroscopic abnormalities were found during necropsy.

An LD50 of above 2000 mg/kg bw was determined for male and female rats.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute oral and dermal toxicity, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP), as amended for the tenth time in Regulation (EU) No 2017/776.