Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
06 March 2001 - 22 March 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
1996
Qualifier:
according to guideline
Guideline:
other: European Community (EC), Council Directive 67/548/EEC, Annex V, Part B, Methods for the Determination of Toxicity, as last amended by Commission Directive 96/54/EC, Annex IV B, B. 1 tris: "Acute Toxicity (Oral) - Acute Toxic Class Method".
Version / remarks:
1996
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
439-270-3
EC Name:
-
Cas Number:
260408-02-4
Molecular formula:
CAS formula: (C12 H10 O4 S . C6 H6 O . Cl5 P . Cl H4 N)x Molecular formula of the reaction products: (C12 H10 N O2 P)n (n=3-15)
IUPAC Name:
439-270-3
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): SPS-100
- Physical state: White to pale yellow powder
- Storage condition of test material: In refrigerator (0-14°C) in the dark
Stable

Test animals

Species:
rat
Strain:
other: Wistar
Remarks:
Crl:(Wl) BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at the initiation of dosing: Young adult animals (approx. 10 weeks old)
- Weight at the initiating of dosing: 379 - 417g(Males) and 211 - 241g (females)
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.
- Housing: Group housing of 3 animals of the same dosing group in polycarbonate cages (Macrolon MIV type), containing purified sawdust as bedding material.
- Diet: Pelleted rodent diet (Altromin (code VRF 1), Lage, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
METHOD: Oral gavage
Frequency: single dosage, on Day 1.

VEHICLE
The vehicle was selected based on trial preparations.

DOSAGE PREPARATION
The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of vehicle.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 animals. The first group was treated at a dose level of 2000 mg/kg body weight. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were to be taken into account for determination of the time interval between the dose groups.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/Moribundity checks: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing and once daily thereafter, until day 15.
- Necropsy of survivors performed: All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
- Other examinations performed: none.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 3; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels: Lethargy, hunched posture, rales, uncoordinated movements and/or chromodacryorrhoea were noted among the animals between days 1 and 3.
Body weight:
The mean 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:
GHS criteria not met
Conclusions:
In an acute oral toxicity study performed according to OECD 423 and in accordance with GLP principles, an LD50 of >2000 mg/kg bw was determined
Executive summary:

The acute oral toxicity of SPS-1 00 was determined in accordance with OECD guideline 423 and according to GLP principles. The substance was administered by oral gavage to two consecutive groups of 3 Wistar Han rats of each sex at 2000 mg/kg body weight. No mortality occurred. Lethargy, hunched posture, rales, uncoordinated movements and/or chromodacryorrhoea were noted among the animals between days 1 and 3. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The acute oral toxicity (LD50) was determined to be > 2000 mg/kg bw.