Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
28 February 2001 - 14 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 402 (Acute Dermal Toxicity)
Version / remarks:
1987
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 92/69/EEC, B.3: "Acute Toxicity-Dermal"
GLP compliance:
yes
Test type:
fixed dose procedure
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:
Wistar
Remarks:
Crl:(WI) 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. 9 weeks old)
- Weight at the initiating of dosing: 348 - 369g (Males) and 206 - 256g (females)
- Housing: Individually housed in polycarbonate cages, 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

Type of coverage:
semiocclusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
The formulation was applied to a area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. Animals were clipped the day before application. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminium foil and Coban flexible bandage. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg (10 ml/kg) body weight.

Duration of exposure:
24h
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: 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
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels: Lethargy, chromodacryorrhoea, ptosis, cramped posture, diarrhoea and/or tremors were noted among the animals between days 1 and 5. Hunched posture and/or piloerection
were noted among the animals between days 1 and 12.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
Signs of toxicity (local): General erythema was seen in the treated skin-area of one female between days 2 and 4.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study performed according to OECD 402 and in accordance with GLP principles, an LD50 of >2000 mg/kg bw was determined.
Executive summary:

The acute dermal toxicity of SPS-100 was determined in accordance with OECD guideline 402 and according to GLP principles. SPS-100 was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. No mortality occurred. Lethargy, chromodacryorrhoea, ptosis, cramped posture, diarrhoea and/or tremors were noted among the animals between days 1 and 5. Hunched posture and/or piloerection were noted among the animals between days 1 and 12. General erythema was seen in the treated skin-area of one female between days 2 and 4. 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 dermal toxicity (LD50) was determined to be > 2000 mg/kg bw.