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Administrative data

Description of key information

Oral (equivalent to OECD 401), rat: LD50 = 620.42 mg/kg bw
Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw (limit test)

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:
09 Apr - 02 May 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
No information on purity was given.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1981
Deviations:
yes
Remarks:
No information on purity was given.
GLP compliance:
no
Remarks:
Basic documentation of quality assurance of experimental procedures and study report available, but not comparable to nowadays GLP provisions
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Remarks:
BOR: WISW (SPF TNO)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 199.4 - 247.0 g (males), 150.0 - 187.2 g (females)
- Fasting period before study: food was withdrawn 16 h prior to and approx. 4 h after dosing.
- Housing: in groups of maximum 5 in Makrolon cages (Typ III), sawdust was used as bedding material
- Diet: Ssniff-R Alleindiät für Ratten (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: minimum 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 50 - 85
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
A range-finding study was carried out to establish a dosing regimen for the main study.

VEHICLE
- Concentration in vehicle: 25%

MAXIMUM DOSE VOLUME APPLIED: approx. 4 mL/kg bw
Doses:
Range-finding study: 1.0 and 2.5 mL/kg bw (corresponding to 1020 and 2550 mg/kg bw based on density of 1.02 g/cm³); 500 and 750 mg/kg bw
Main study: 250, 500, 750 and 1000 mg/kg bw
No. of animals per sex per dose:
Range-finding study: 2 females
Main study: 5 males and 5 females
Control animals:
no
Details on study design:
Range-finding study:
- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed 20 min and 1, 2, 3, 6, 24 and 48 h after administration and subsequently once daily for 14 days.

Main study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 20 min and 1, 2, 3, 6, 24 and 48 h after administration and subsequently once daily for 14 days. Individual body weights were determined on Days 0 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Probit Analysis according to Finney (1971) was used to calculate the orale LD50 values.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
620.42 mg/kg bw
Based on:
test mat.
Mortality:
Range-finding study: All animals died at approx. 1020 and 2550 mg/kg bw within 24 h after administration. No mortality occurred at 500 and 750 mg/kg bw.

Main study: At 250 mg/kg bw no mortality occurred during the study period. At 500 mg/kg bw three animals died within 3 days after administration. At 750 mg/kg bw five animals died within 6 days after administration. At 1000 mg/kg bw all animals died within 3 days after administration.
Clinical signs:
Main study: The test substance induced apathy, posture anomalies, ataxia, decreased excitability, piloerection, ptosis and dark red coloured urine. The symptoms occurred in surviving animals approx. 20 min post administration and continued with first increasing then decreasing intensity until 48 hours post administration. The surviving animals recovered completely whereas animals which died before study termination showed the symptoms with constant intensity until exitus.
Body weight:
At the end of the observation period all surviving animals showed the expected body weight gain.
Gross pathology:
Gross pathological examination of dead animals revealed partially severe gastrointestinal haemorrhages and one urinary bladder filled with bloody urin.
Post mortem examination of rats surviving until scheduled sacrifice on Day 14 revealed no abnormalities.

Table 1. Results of the acute toxicity study.

Group

Dose level (mg/kg bw)

Mortality

24 h

48 h

7 days

6/14 days

m

f

m

f

m

f

m

f

I

250

0/5

0/5

0/5

0/5

0/5

0/5

0/5

0/5

II

500

0/5

0/5

0/5

1/5

1/5

2/5

1/5

2/5

III

750

0/5

3/5

0/5

3/5

1/5

3/5

1/5

4/5

IV

1000

2/5

4/5

3/5

5/5

5/5

5/5

5/5

5/5

Interpretation of results:
other: Acute Tox. Cat. 4 according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study a LD50 value of 620.42 mg/kg bw in male and female rats was calculated according to the method of Finney.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
620.42 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1992
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Remarks:
CD (Crl : CD (SD) IGS BR)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: approx. 8 - 12 weeks
- Weight at study initiation: 212 - 236 g (males), 211 - 231 g (females)
- Housing: individually during the 24 h exposure period and subsequently 5 animals of the same sex per cage in polypropylene cages, bedding woodflakes
- Diet: Rat and Mouse Expanded Diet No.1 (Special Diets Services Limited, Witham, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks
- % coverage: 10%
- Type of wrap if used: The treated skin was covered with a surgical gauze which was held in place with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: The skin was wiped with cotton wool moistened with distilled water to remove residual test substance.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 1.99 mL/kg bw
- Constant concentration used: yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed 30 min and 1, 2 and 4 h after administration and subsequently once daily for 14 days. Individual body weights were determined on Days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation.
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:
No signs of systemic toxicity were noted during the study.
Body weight:
All animals showed an expected gain in body weight during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
No signs of skin irritation were noted during the study.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute dermal toxicity study a LD50 value > 2000 mg/kg bw in male and female rats was found.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Oral

The acute oral toxicity of the test substance was assessed in an acute toxicity test equivalent to OECD Guideline 401 (1984). A range-finding study was performed to determine the appropriate dose level of the test substance for the main study. Two female Wistar rats per dose group received once 1.0 or 2.5 mL/kg bw undiluted test substance (equivalent to approx. 1020 and 2550 mg/kg bw) or 500 or 750 mg/kg bw test substance at concentration of in arachis oil. All animals at dose level of approx.1020 and 2550 mg/kg bw died within 24 h after administration. No mortality occurred at 500 and 750 mg/kg bw.

Based on the results of the range-finding study, five male and five female Wistar rats per dose group received 250, 500, 750 or 1000 mg/kg bw test substance at concentration of 25% in arachis oil once by oral gavage. Animals were observed 20 min and 1, 2, 3, 6, 24 and 48 hours after administration and subsequently once daily for 14 days. Furthermore, individual body weights were determined on Days 0 and 14 and macroscopic examination was performed on test Day 14 at terminal sacrifice. No mortality occurred at 250 mg/kg bw during the study period. At 500 mg/kg bw three animals died within 3 days, at 750 mg/kg bw five animals died within 6 days and all animals died at 1000 mg/kg bw within 3 days after administration. Clinical signs such as apathy, posture anomalies, ataxia, decreased excitability, piloerection, ptosis and dark red coloured urine were observed as a result of the treatment. The symptoms occurred in surviving animals reaching a peak intensity between 20 min and 48 h after administration. Animals which died before study termination showed the aforementioned clinical signs with constant intensity until exitus. Based on the results of this study, the LD50 value was calculated to be 620.42 mg/kg bw in rats.

Dermal

The acute dermal toxicity of the test substance was assessed in a limit test performed in 5 male and 5 female Sprague-Dawley rats according to OECD Guideline 402 and in compliance with GLP (1999). A single dose of 2000 mg/kg bw of the test substance was applied to the clipped skin of rats under semi-occlusive conditions for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice on Day 15. There was no mortality, no effects on body weight gain and no signs of skin irritation during the 14-day observation period. No abnormalities were found at macroscopic post mortem examination of the animals. The LD50 value for dermal toxicity is considered to be > 2000 mg/kg bw.


Justification for classification or non-classification

The available data on acute oral toxicity of the test substance meet the criteria for Acute Tox. Cat 4 (H302) according to Regulation (EC) 1272/2008.

The available data on acute dermal toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.