Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral (OECD 401): LD50 (rat, m/f) = 1106 mg/kg bw (1319.39 mg/kg bw (males) and 908.3 mg/kg bw (females))

Dermal (OECD 402): LD50 (rat, m/f) > 2000 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:
1989-10-23 to 1989-11-24
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
adopted 24 Feb 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Version / remarks:
Version: March 1984
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Biological Research Laboratories Ltd., Fuellinsdorf, Switzerland
- Age at start of treatment: 9-10 weeks (males), 11-12 weeks (females)
- Weight at study initiation: 175-224 g (males), 162-194 g (females)
- Fasting period before study: 15 to 22 hours (food was again presented approximately one hour after dosing)
- Housing: 5 animals/cage
- Diet: pelleted standard Kliba 343 (Kliba Klingentalmuehle, Kaiseraugst, Switzerland), ad libitum
- Water: community tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 Oct 1989 To: 24 Nov 1989
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
200, 800 and 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: 15 days
- Frequency of observations: mortality / viability: Four times during test Day 1, and daily during Days 2 - 15; clinical signs: Each animal was examined for changes in appearance and behaviour four times during Day 1, and daily during Day 2-15.
- Frequency of weighing: Day 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
The LOGIT-Model was applied to estimate the toxicity value. Additionally, the 90, 95 and 99% confidence limits for the toxicity for each sex and the slope of the dose response line were estimated.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
1 319.39 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 90% confidence limit: 527.57 - 5746.58 mg/kg bw
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
908.3 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 90% confidence limit: 453.09 - 3163.45 mg/kg bw
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 106.12 mg/kg bw
Based on:
test mat.
95% CL:
> 682.22 - < 2 170.79
Mortality:
at 200 mg/kg bw: no mortality.
at 800 mg/kg bw: 2/5 males (Day 1 and 2) and 1/5 female (Day 1).
at 2000 mg/kg bw: 3/5 males (2 on Day 1 and 1 on Day 2) and 5/5 females (2 on Day 1 and 3 on Day 2)
Clinical signs:
other: 200 mg/kg bw: males/females - no clinical signs noted. 800 mg/kg bw: 3/5 males and 2/5 females sedated, ruffled fur in 5/5 males and 1/5 females, hunched posture/recumbency in 3/5 males and 1/5 females; all signs were fully reversible by study Day 4 (male
Gross pathology:
200 mg/kg bw: dark red discoloration of lungs in 1/5 males and pale discoloration of lungs in 1/5 females.
800 mg/kg bw: dark red discoloration of lungs in each 1/5 males and females.
2000 mg/kg bw: dark red discoloration of lungs in 3/5 males, dark red discoloration of jejunum, duodenum, ileum and caecum in 1/5 male, as well as dark or light red discoloration of lungs in 2/5 females and reddish discoloration of duodenum and jejunum in 1/5 females.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of the test, the acute oral LD50 value was 1106 mg/kg bw in both sexes combined, 1319.39 mg/kg bw in males and 908.3 mg/kg bw in females.
CLP: Acute Oral 4, H302 according to Regulation (EC) No. 1272/2008 (CLP/EU GHS)
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 106 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable (Klimisch score 1) study with the registered substance. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, Item 8.5, of Regulation (EC) No. 1907/2006 (REACH).

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:
1989-10-26 to 1989-11-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 24 Feb 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
Version: March 1984
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Biological Research Laboratories Ltd., Fuellinsdorf, Switzerland
- Age at start of treatment: 10 weeks (males) and 12 weeks (females)
- Weight at study initiation: 243 - 264 g (males), 194 - 216 g (females)
- Housing: individually
- Diet: pelleted standard Kliba 343 (Kliba Klingentalmuehle, Kaiseraugst, Switzerland), ad libitum
- Water: community tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on dermal exposure:
TEST SITE
- Area of exposure: clipped area on the backs of the animals
- % coverage: approximately 10%
- Type of wrap if used: The test article was applied evenly on the skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treated skin was washed with lukewarm tap water and dried with disposable paper towels.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 4 mL at 2000 mg/kg bw

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: 15 days
- Frequency of observations: mortality / viability: Four times during test Day 1, and daily during Day 2 - 15; clinical signs: Each animal was examined for changes in appearance and behavior four times during Day 1, and daily during Day 2-15.
- Frequency of weighing: Test days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
Due to the 24 h semi-occlusive treatment, the local skin effects were observed starting on Day 2 of the test.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
other:
Body weight:
other body weight observations
Remarks:
The body weight gain of the animals was not affected throughout the study by test article treatment.
Gross pathology:
At 2000 mg/kg bw: dark red lungs in 1/5 females, pale discoloration of lungs in 1/5 females.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the tested conditions, the acute dermal LD50 value in male and female rats was > 2000 mg/kg bw.
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable (Klimisch score 1) study with the registered substance. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, Item 8.5, of Regulation (EC) No. 1907/2006 (REACH).

Additional information

Acute oral toxicity:

A study assessing the acute oral toxicity of the test item was performed in Wistar rats according to OECD guideline 401 and in compliance with GLP (90-0530-DGT). The test substance was dissolved in polyethylene glycol (PEG 400) and administered by oral gavage. Groups of 5 rats/sex received test item doses of 200, 800 and 2000 mg/kg bw or the corresponding vehicle. After administration, the animals were observed until Day 15 for clinical signs and mortality. The body weight was measured weekly during the study period. At the end of the observation period, gross necropsy was performed on all surviving animals and all animals that died or were sacrificed prior to the end of the observation period.

Mortality was observed in 2/5 males and in 1/5 females at 800 mg/kg bw within the first two study days and in 3/5 males and 5/5 females at 2000 mg/kg bw within 3 days following treatment. Clinical signs of toxicity were noted at 800 and 2000 mg/kg bw. At 800 mg/kg bw, sedation was noted in 3/5 males and 2/5 females, ruffled fur occurred in 5/5 males and 1/5 females, and hunched posture/recumbency in 3/5 males and 1/5 females. At 2000 mg/kg bw, 5/5 males and 4/5 females showed sedation, ruffled fur and hunched posture/recumbency. In the same dose group, 1/5 males and 1/5 females had an impaired motility, breathing disorders were observed in 3/5 males (dyspnea) and in 1/5 males (rales), respectively, and 1/5 males had diarrhea. All surviving animals fully recovered by Day 2 (females) and Day 9 (males). One female at 800 mg/kg bw lost weight on Days 8-15 which was not considered to be treatment-related.

At necropsy, dark red discoloration or pale discoloration of the lungs was noted in 1/5, 1/5 and 3/5 males, and in 1/5, 1/5 and 2/5 females at 200, 800 and 2000 mg/kg bw, respectively. At 2000 mg/kg bw 1/5 males and 1/5 females showed dark red discoloration of the caecum, jejunum and/or duodenum.

Under the conditions of the test, the acute oral LD50 value was 1106 mg/kg bw in both sexes combined, 1319.39 mg/kg bw in males and 908.3 mg/kg bw in females.

 

Acute dermal toxicity:

The test item was assessed for the acute dermal toxicity potential in Wistar rats according to OECD guideline 402 (version adopted in 1987) and in compliance with GLP (90-0532-DGT). The test item was dissolved in polyethylene glycol (PEG 400) and a dose level of 2000 mg/kg bw was applied at a volume of 4 mL/kg bw to the clipped skin area on the back of 5 male and 5 female rats. The skin was exposed for 24 h under semi-occlusive conditions and cleaned with warm water after exposure. During a 15-day observation period, all animals were observed for general health and mortality. The body weight was measured weekly during the study period. At study termination, all animals underwent necropsy.

There was no mortality and no clinical signs of toxicity were observed. All animals showed very slight to well defined erythema (grade 1 and 2) and scales (grade 3) on the treated skin area. The erythema was fully reversible within Day 7 in males and within Day 14 in females. Scales were observed until study termination. The body weight was not affected by the treatment. At scheduled necropsy, dark red lungs was noted in 1/5 females and pale discoloration of the lungs was observed in 1/5 females, respectively.

Under the tested conditions, the acute dermal LD50 value in male and female rats was > 2000 mg/kg bw.

Justification for classification or non-classification

The available data on acute oral toxicity meet the criteria for classification as Acute oral 4 (H302) according to Regulation (EC) No. 1272/2008 (CLP) and according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations.

The available data on acute dermal toxicity do not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.

Based on the criteria of the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations, the registered substance might be classified as category 5 for acute dermal toxicity.

Acute inhalation toxicity: data lacking