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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From the 11th to the 28th January, 1999
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Justification for Read Across is detailed in the section summary and it is further detailed in the report attached to the IUCLID section 13.
Cross-reference
Reason / purpose:
read-across source
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From the 11th to the 28th January, 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
As required by the Dutch Act on Animal Experimentation, the study protocol was reviewed and agreed by the Article 14-functionary and the EthicalCommittee of NOTOX.
Species: Rat, Wistar strain Cr1:(WI) BR (outbred, SPF-Quality).
Source: Charles River Deutschland, Germany
Age and body weight: young adult animals (approx. 6 weeks old). Body weight variation did not exceed +/- 20% of the sex mean.
Identification: earmark
ENVIRONMENTAL CONDITIONS
Conditions: air-conditioned room with approximately 15 air changes per hour
Temperature: 21°C
Relative humidity of 50%.
Fluctuations from these optimal conditions were noted, but were considered not to have affected study integrity.
Lighting: 12 hours artificial fluorescent light and 12 hours dark per day.
Accomodation: group housing of 3 animals per sex per cage
Cage: labelled polycarbonate containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Helmond, The Netherlands).
Certificates of analysis were examined and then retained in the NOTOX archives.
Acclimatisation period: at least 5 days before start of treatment under laboratory conditions.
Diet: free access to standard pelleted laboratory animal diet (from Carfll Quality BVBA, Oud-Turnhout, Belgium).
Certificates of analysis were examined and then retained in the NOTOX archives.
Water Free access to tap-water.
Certificates of quarterly analysis were examined and then retained in the NOTOX archives.
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Method of gavage: with stainless stomach tube
Fasting: food was withheld overnight prior to dosing until approximately 3-4 hours after administration of the test substance.
Doses:
2000 mg/kg (10 ml/kg) body weight
Frequency: single dose at day 1
No. of animals per sex per dose:
6 Animals.
Each dose group consisted of 3 animals of one sex (females were numparous and non-pregnant).
Details on study design:
OBSERVATIONS
Mortality/Viability: twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded: Maximum grade 4: grading slight (1) to very severe (4) Maximum grade 3: grading slight (1) to severe (3) Maximum grade 1: presence is scored (1).
Necropsy: at the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
INTERPRETATION
The test substance was ranked within LD50 value ranges of 0-25, 25-200, 200-2000 or exceeding 2000 mg/kg body weight.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise L050 value).
Preliminary study:
12 January 1999: 2000 mg/kg, females
14 January 1999: 2000 mg/kg, males
The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guideiines.
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No clinical signs of systemic toxicity were noted in any of the animals. Brown and/or black staining of the neck and/or tail by the test substance was noted among the animals during the study period.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
other: not classified
Remarks:
Classification criteria according to the CLP Regulation 1272/2008 and its amendments
Conclusions:
LD50> 2000 mg/kg body weight
Executive summary:

The Acute Toxic Class Method study was carried out based on the guidelines described in: EC Commission Directive 96/54/EC, Part B.1 tris “Acute Toxicity-Oral, Acute Toxic Class Method" and OECD No 423, “Acute Oral Toxicity - Acute Toxic Class Method".

The similar subtance was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminai sacrifice (day 15). No mortality occurred. No clinical signs of systemic toxicity were noted in any of the animals. Brown and/or black staining of the neck and/or tail by the test substance was noted among the animals during the study period. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of the similar substance in Wistar rats was established to exceed 2000 mg/kg body weight.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report Date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Expiry date: 29 August 2002
Storage condition: at room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
As required by the Dutch Act on Animal Experimentation, the study protocol was reviewed and agreed by the Article 14-functionary and the EthicalCommittee of NOTOX.
Species: Rat, Wistar strain Cr1:(WI) BR (outbred, SPF-Quality).
Source: Charles River Deutschland, Germany
Age and body weight: young adult animals (approx. 6 weeks old). Body weight variation did not exceed +/- 20% of the sex mean.
Identification: earmark
ENVIRONMENTAL CONDITIONS
Conditions: air-conditioned room with approximately 15 air changes per hour
Temperature: 21°C
Relative humidity of 50%.
Fluctuations from these optimal conditions were noted, but were considered not to have affected study integrity.
Lighting: 12 hours artificial fluorescent light and 12 hours dark per day.
Accomodation: group housing of 3 animals per sex per cage
Cage: labelled polycarbonate containing purified sawdust as bedding material (Woody SPF, supplied by B.M.I., Helmond, The Netherlands).
Certificates of analysis were examined and then retained in the NOTOX archives.
Acclimatisation period: at least 5 days before start of treatment under laboratory conditions.
Diet: free access to standard pelleted laboratory animal diet (from Carfll Quality BVBA, Oud-Turnhout, Belgium).
Certificates of analysis were examined and then retained in the NOTOX archives.
Water Free access to tap-water.
Certificates of quarterly analysis were examined and then retained in the NOTOX archives.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Method of gavage: with stainless stomach tube
Fasting: food was withheld overnight prior to dosing until approximately 3-4 hours after administration of the test substance.
Doses:
2000 mg/kg (10 ml/kg) body weight
Frequency: single dose at day 1
No. of animals per sex per dose:
6 Animals.
Each dose group consisted of 3 animals of one sex (females were numparous and non-pregnant).
Details on study design:
OBSERVATIONS
Mortality/Viability: twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.
The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded: Maximum grade 4: grading slight (1) to very severe (4) Maximum grade 3: grading slight (1) to severe (3) Maximum grade 1: presence is scored (1).
Necropsy: at the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
INTERPRETATION
The test substance was ranked within LD50 value ranges of 0-25, 25-200, 200-2000 or exceeding 2000 mg/kg body weight.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise L050 value).

Results and discussion

Preliminary study:
12 January 1999: 2000 mg/kg, females
14 January 1999: 2000 mg/kg, males
The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guideiines.
Effect levels
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
No clinical signs of systemic toxicity were noted in any of the animals. Brown and/or black staining of the neck and/or tail by the test substance was noted among the animals during the study period.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Remarks:
Classification criteria according to the CLP Regulation 1272/2008 and its amendments
Conclusions:
LD50> 2000 mg/kg body weight
Executive summary:

The acute oral toxicity test was performed on a similar substance 01 (read-across from supporting substance -structural analogue or surrogate).

The Acute Toxic Class Method study was carried out based on the guidelines described in: EC Commission Directive 96/54/EC, Part B.1 tris “Acute Toxicity-Oral, Acute Toxic Class Method" and OECD No 423, “Acute Oral Toxicity - Acute Toxic Class Method".

The similar subtance was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminai sacrifice (day 15). No mortality occurred. No clinical signs of systemic toxicity were noted in any of the animals. Brown and/or black staining of the neck and/or tail by the test substance was noted among the animals during the study period. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of the similar substance in Wistar rats was established to exceed 2000 mg/kg body weight.