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Administrative data

Description of key information

The oral LD50 for the test item was estimated to be 939.8 mg/kg for female rats.

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
2001
Deviations:
yes
Remarks:
1 deviation reported. Considered uncritical.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
yes
Remarks:
1 deviation reported. Considered uncritical.
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Haskell Sample Number 26185
- Purity: 99.90%
- Physical characteristics: white to amber solid
Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Raleigh, North Carolina
- Age at study initiation: 10 or 11 wks on the day of dosing
- Weight at study initiation: 217.0 to 257.1 g (range obtained from Individual Body Weights table provided in Appendix A. Recorded weights were from before fasting)
- Fasting period before study: approximately 17-18 hrs prior to dosing
- Housing: Housed individually in polycarbonate pans containing bedding or in stainless steel, wire-mesh cages suspended above cage boards
- Diet: ad libitum, PMI Nutrition International, LLC Certified Rodent LabDiet 5002
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26 °C
- Humidity (%): 30-70%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): Fluorescent light, apprx 12-hr light/dark cycle

IN-LIFE DATES: From: Jan 16, 2004 To: Mar 3, 2004
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Not specified
- Amount of vehicle: 10 mL/kg bw
- Preparation: dosing suspensions were stirred prior to and throughout dosing procedure

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg
Doses:
175, 500, 2000 mg/kg bw
No. of animals per sex per dose:
5 animals at 2000 mg/kg bw
1 animal at 175 mg/kg bw
3 animals at 550 mg/kg bw
Control animals:
no
Details on study design:
- Rats dosed one at a time at a minimum of 48-hr intervals
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations made daily during course of study. Animal weights takes on test days -1, 0, 7 and 14.
- Necropsy of survivors performed: Yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: Signs of illness, injury, or abnormal behavior.
Statistics:
Software package (A0T425StatPgm) used to determine dose progression and to calculate the LD50
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 939.8 mg/kg bw
95% CL:
ca. 550 - ca. 2 000
Mortality:
All rats dosed at 2000 mg/kg were found dead by the day after dosing
Clinical signs:
- Clinical signs observed in rats dosed at 2000 mg/kg include tremors, staining, clear oral discharge, hair loss, wet chin, arching back during handling, or ataxia.
- 1 rat dosed at 550 mg/kg showed no clinical signs during the study. The remaining 2 rats in the dose group exhibited diarrhea, hair loss, staining, red nasal discharge, or wet fur during the study.
- No clinical signs observed in rat dosed at 175 mg/kg
Body weight:
No body weight loss occurred in surviving rats
Gross pathology:
No gross lesions were present in the rats at necropsy
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Under the conditions of the study, the oral LD50 for the test item was estimated to be 939.8 mg/kg for female rats.
Executive summary:

The acute oral toxicity of the test item was assessed via an up-and-down procedure which followed the OECD 425 TG (2001). In brief, fasted female rats were individually dosed with the test item (suspended in corn oil) via intragastric intubation. The doses selected were 2000, 550, and 175 mg/kg. The maximum starting dose was chosen based on available toxicity data. Dosed rats were observed for mortality, body weight changes, and clinical signs for up to 14 days post-treatment. Surviving rats were necropsied to assess gross pathological effects. All rats treated with the starting dose (2000 mg/kg) were found dead by the day after dosing. Clinical signs in this dose group included tremors, staining, clear oral discharge, hair loss, wet chin, arching back during handling or ataxia. In the 500 mg/kg dose group, clinical signs such as diarrhea, hair loss, staining, red nasal discharge, or wet fur were observed. No clinical signs were observed in the rat dosed at 175 mg/kg. No gross lesions were present in the rats at necropsy. Based on the results of the study, the oral LD50was estimated to be 939.8 mg/kg in female rats.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
939.8 mg/kg bw

Additional information

Justification for classification or non-classification

Acute Oral Toxicity

The acute oral toxicity (LD50) of the substance is approximately 939.8 mg/kg bw. According to CLP (EC 1272/2008) criteria, this substance is classified as Acute Toxicity (oral) Category 4.

Acute Inhalation Toxicity

Data for classification lacking.

Acute Dermal Toxicity

Data for classification lacking

Specific Target Organ Toxicity - Single Exposure (STOT - SE)

No toxicologically significant signs were reported following single exposure to the substance. Therefore, the substance does not meet the CLP (EC 12/72/2008) criteria for STOT-SE classification.