Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
1 (reliable without restriction)

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:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Diphenylsulfon (DPS)
- Substance type: organic
- Physical state: solid, white powder
- Analytical purity: >99%
- Purity test date: 15/05/2001
- Lot/batch No.: 1712SA
- Expiration date of the lot/batch: 15/05/2002
- Stability under test conditions: not indicated
- Storage condition of test material: At room temperature in the dark
- Other: bulk density: 0.7-0.8
Stability in vehicle, propylene glycol: not indicated

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: body weight variation did not exceed +- 20% of the sex mean.
- Fasting period before study:
- Housing: individually housed in labelled polycarbonate cages (type III, height 15 cm) containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
- Diet (e.g. ad libitum): Free acces to standard pelleted animal laboratory diet (from Altromin (code VRF 1), Lage, Germany). Certificates of analysis were examined and then retained in the NOTOX archives.
- Water (e.g. ad libitum): Free acces to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.
- Acclimation period: at least 5 days before start of treatment


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+-3°c
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs artificial fluorescent light


IN-LIFE DATES: From: 26 september 2001 To: 10 october 2001

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: 25 cm² for males and 18 cm² for females
- % coverage: approximately 10
- Type of wrap if used: 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.
( * manufactures: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).


REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was cleaned of residual test substances, using water
- Time after start of exposure: 24h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution): 2000 mg/kg (10 ml/kg) body weight
- Constant volume or concentration used: yes
- For solids, paste formed: yes


VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):2000 mg/kg
- Lot/batch no. (if required):
- Purity:
Duration of exposure:
24 h
Doses:
2000 mg/kg (10 ml/kg) body weight
No. of animals per sex per dose:
5 males and 5 females (females were nulliparous and non-pregnant
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
* Mortality/viability: Twice daily. The time of death was recorded as precisely as possible.
* Body weights: Days 1 (pre-administration), 8 and 15 and at death (if found dead after day 1).
* Clinical signs: at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: prescence is scored (1)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
no statistical analysis was performed

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
One male was found death on day1 and one male was found dead on day 2. No further mortality occured.
Clinical signs:
Lethargy, hunched posture, tremor, piloerection, chromodacryorrhoea, hypothermia, laboured respiration and/or uncoordinated movements were noted among the animals beteen days 1 and 8.
Scales, erythema and/or swelling were seen in the treated skin-area of the females during the observation period. Scales were seen in one male on day 3.
Body weight:
The changes noted in body weight gain in male and females were within the range expected for rats used in this type of study and were therefore considered not indcative of toxicity.
Gross pathology:
Macroscopic findings: At macroscopic post mortem examination, hemorrhagic cysts were found in the ovaries of one female. Macroscopic examination of the animals that died during the study and of the surviving animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 value of DIPHENYLSULFON (DPS) in Wistar rats was established to exceed 2000 mg/kg bodyweight.
Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), DIPHENYLSULFON, (DPS) does not have to be classified and has no obligatory labelling requirement for dermal toxicity.