Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral

Under the conditions of this study the acute lethal oral dose was found to be greater than 2000 mg/kg bodyweight.

Dermal

Under the conditions of this study, the LD50 has been determined to be greater than 2000 mg/kg bodyweight.

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:
16 July 1987 to 30 July 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
not specified
Remarks:
The study was conducted in accordance with quality assurance procedures.
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Remarks:
CD [Crl: COBS CD (SD) BR]
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: Four to six weeks old
- Weight at study initiation: 104 to 120 grams
- Fasting period before study: Overnight before dosing and for four hours post dosing (restricted access to food only)
- Housing: Rats were allocated to cages within the treatment group, housed in groups by sex in metal cages with wire mesh floors.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 to 22 °C
- Humidity: 69 % (relative)
- Air changes: Approximately 15 per hour
- Photoperiod: 12 hours of artificial light in each 24 hour period
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 % (w/v)
- Stability: Not determined; the test material was prepared on the day of dosing

MAXIMUM DOSE VOLUME APPLIED: 10.0 mL/kg
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males and 5 females per dose
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 day 1. On subsequent days, observations took place twice daily. Individual bodyweights were recorded on days 1, 8 and 15.
- Necropsy of survivors performed: All animals were killed on day 15 by cervical dislocation and macroscopic post mortem examination took place which consisted of opening the abdominal and thoracic cavities.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
not determinable due to absence of adverse toxic effects
Mortality:
There were no deaths following a single oral dose of test material at 2000 mg/kg bodyweight.
Clinical signs:
Signs of reaction to treatment observed shortly after dosing in all animals were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy and pallor of extremities. Recovery, as judged by external appearance and behaviour, was advanced by Day 2 and complete by Day 3.
Body weight:
Slightly low bodyweight gains were recorded for the majority of animals on Day 8. Anticipated bodyweight gains were recorded for all animals on day 15.
Gross pathology:
Terminal autopsy findings were normal.

Table 1: Signs of reaction to treatment observed

Signs

No. of animals in group of 5 showing signs at 2000 mg/kg

Male

Female

Pilo-erection

5

5

Hunched posture

5

5

Waddling

5

5

Lethargy

5

5

Pallor of extremities

5

5

Table 2: Individual bodyweights

Sex

Bodyweight (g) at Day

1

8

15

Male

120

104

120

112

119

195

163

186

175

182

248

207

234

229

236

Female

107

114

111

119

112

147

152

148

169

155

169

182

173

197

184

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of this study the acute lethal oral dose was found to be greater than 2000 mg/kg bodyweight.
Executive summary:

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 401 and EU Method B1.

A group of 5 male and 5 female rats were exposed to the test material in corn oil at a limit dose of 2000 mg/kg bw. Fasted animals were dosed via a syringe and plastic catheter. All animals were observed for 14 days after dosing before being terminated on day 15 and subjected to macroscopic examination at necropsy.

There were no cases of mortality during the study. Signs of reaction to treatment observed shortly after dosing in all animals were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy and pallor of extremities. Recovery, as judged by external appearance and behaviour, was advanced by Day 2 and complete by Day 3. Terminal autopsy findings were normal.

Under the conditions of this study the acute lethal oral dose was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
One study is available to address this endpoint. The study was performed in accordance with standardised guidelines. The quality of the database is therefore considered to be good.

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:
14 July 1987 to 28 July 1987
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
GLP compliance:
not specified
Remarks:
The study was conducted in accordance with quality assurance procedures.
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Remarks:
CD [Crl: COBS CD (SD) BR]
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 7 to 10 weeks of age
- Weight at study initiation: 201 to 226 grams
- Fasting period before study: No
- Housing: Rats were allocated to cages within the treatment group. The rats were housed individually in metal cages with wire mesh floors.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 to 22 °C
- Humidity: 69 % (relative)
- Air changes: Approximately 15 per hour
- Photoperiod: 12 hours of artificial light in each 24 hour period
Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorso-lumbar region (hair was removed with electric clippers on the day prior to application; no shaving or chemical depilation was used)
- % coverage: 10 % of the total body surface
- Type of wrap if used: Gauze used to cover the treated area was held in place with an impermeable dressing encircled firmly around the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Warm (30 to 40 °C) water was used to wash the area before blotting it with absorbent paper.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 g/kg at a volume of 2.60 mL/kg
- Concentration (if solution): 76.9 % w/v in distilled water
- For solids, paste formed: Yes; prepared as a 76.9 % w/v paste in distilled water on the day of dosing
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 animals per sex per dose
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 twice daily. The treated areas of skin were examined daily for signs of dermal irritation and assessed for erythema and eschar and oedema formation. Bodyweights were recorded on Days 1, 8 and 15.
- Necropsy of survivors performed: Yes; on day 15 all animals were killed by cervical dislocation and subjected to macroscopic post mortem examination which consisted of opening the abdominal and thoracic cavities.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
There were no deaths following the application of the test material.
Clinical signs:
There were no clinical signs of systemic reaction to treatment.
Body weight:
Slightly low bodyweight gains were recorded for one male and three females on Day 15. All other animals achieved anticipated bodyweight gains throughout the study.
Gross pathology:
Terminal autopsy findings were normal.
Other findings:
DERMAL RESPONSES
At the site of application of the test material no irritation responses or dermal changes were observed.
Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of this study, the LD50 has been determined to be greater than 2000 mg/kg bodyweight.
Executive summary:

A study was conducted to investigate the acute dermal toxicity of the test material in accordance with the standardised guidelines OECD 402 and EU Method B.3.

Five male and 5 female rats received a dermal administration of the test material (as a paste made with distilled water) at a limit dose of 2000 mg/kg bodyweight. Gauze used to cover the treated area was held in place with an impermeable dressing encircled firmly around the trunk. The animals were exposed to the test material for 24 hours before it was washed off with warm water and blotted with absorbent paper. All animals were observed for 14 days after dosing before being terminated on day 15 and subjected to macroscopic examination at necropsy.

All animals survived to study termination and there were no clinical signs of toxicity noted throughout the 14-day study period. Slightly low bodyweight gains were recorded for one male and three females on Day 15. All other animals achieved anticipated bodyweight gains throughout the study. There were no gross pathological findings observed in any animals in the terminal autopsy.

Under the conditions of this study, the LD50 has been determined to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
One study is available to address this endpoint. The study was performed in accordance with standardised guidelines. The quality of the database is therefore considered to be good.

Additional information

Oral

The acute oral toxicity of the test material was investigated in accordance with the standardised guidelines OECD 401 and EU Method B1. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

A group of 5 male and 5 female rats was exposed to the test material in corn oil at a limit dose of 2000 mg/kg bw. Fasted animals were dosed via a syringe and plastic catheter. All animals were observed for 14 days after dosing before being terminated on day 15 and subjected to macroscopic examination at necropsy.

There were no cases of mortality during the study. Signs of reaction to treatment observed shortly after dosing in all animals were pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethargy and pallor of extremities. Recovery, as judged by external appearance and behaviour, was advanced by Day 2 and complete by Day 3. Terminal autopsy findings were normal.

Under the conditions of this study the acute lethal oral dose was found to be greater than 2000 mg/kg bodyweight.

Inhalation Toxicity

In accordance with section 8.5.2 of Column 2 of REACH Annex VIII, testing via the inhalation route is appropriate if exposure of humans via inhalation is 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. For the test material, exposure via the inhalation route is unlikely and it is therefore considered justified to omit this study.

 

Dermal

A study was conducted to investigate the acute dermal toxicity of the test material in accordance with the standardised guidelines OECD 402 and EU Method B.3. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Five male and 5 female rats received a dermal administration of the test material (as a paste made with distilled water) at a limit dose of 2000 mg/kg bodyweight. Gauze used to cover the treated area was held in place with an impermeable dressing encircled firmly around the trunk. The animals were exposed to the test material for 24 hours before it was washed off with warm water and blotted with absorbent paper. All animals were observed for 14 days after dosing before being terminated on day 15 and subjected to macroscopic examination at necropsy.

All animals survived to study termination and there were no clinical signs of toxicity noted throughout the 14-day study period. Slightly low bodyweight gains were recorded for one male and three females on Day 15. All other animals achieved anticipated bodyweight gains throughout the study. There were no gross pathological findings observed in any animals in the terminal autopsy.

Under the conditions of this study, the LD50 has been determined to be greater than 2000 mg/kg bodyweight.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute toxicity via the oral or dermal route.