Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13th February 2008- 27th February 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
484-490-5
EC Name:
-
Molecular formula:
Hill formula:C21 H12 N2 O6 S Sr 5/2(H2O) CAS formula: C21 H14 N2 O6 S . Sr
IUPAC Name:
484-490-5
Test material form:
solid: granular
Details on test material:
Red Powder.
Batch-070711
Purity>=96.4 %
Storage-Room temperature in the dark.
Stable under storage conditions.
Epiry date-11 July 2011

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfield, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 weeks old
- Weight at study initiation: Does not exceed the mean.
- Fasting period before study: Not specified.
- Housing: Animals were housed individually in labelled Macrolon cages containing sterilized sawdust as bedding material and paper as cage- enrichment.
- Diet (e.g. ad libitum): Free access to pelleted rodent diet.
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7 - 21.6 °C
- Humidity (%): 39 - 63 %
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light and 12 hours darkness per day.

IN-LIFE DATES: From: 13 February 2008 To: 27 February 2008

Administration / exposure

Type of coverage:
occlusive
Vehicle:
propylene glycol
Details on dermal exposure:
TEST SITE
- Area of exposure: Back
- % coverage: 10 %
- Type of wrap if used: Covered with aluminium foil and Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance removed with tap water.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (10 mL/kg)


Duration of exposure:
24 Hours
Doses:
Single dose
No. of animals per sex per dose:
5 animals per sex per dose.
Control animals:
not specified
Details on study design:
Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were measured on Day 1, 8 and 15. Clinical observations were recorded daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other

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:
No mortality occurred.
Clinical signs:
Hunched posture, piloerection and/or chromodacryorrhoea were noted among both males and females. In addition, lethargy, flat posture, uncoordinated movements, quick breathing, shallow respiration, ptosis and/or hypothemia were noted in all males. The animals had recovered from the symptoms between Days 2 and 3.

These symptoms were occasionally seen in dermal toxicity studies. Based on their mild nature and short duration, these symptoms were considered to be of no toxicological significance.

Scales and/or scabs were seen in the treated skin area of the majority of females during the observation period.

Red staining of the treated skin area and/or other body parts of the animals was noted during the observation period and was considered to be related to staining properties of the test substance.
Body weight:
The changes noted in the body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered no indicative of toxicity.
Gross pathology:
At macroscopic post mortem examination, isolated grey/white foci, enlargement and dark red discoloration were found in the papillary process in the liver of one male. Macroscopic post mortem examination of the other animals at termination did not reveal any abnormalities.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of R507-2 in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, R507-2 does not have to be classified and has no obligatory labelling requirement for dermal toxicity according to the GHS of Classification and labelling of Chemicals of the United nations (2004) and EC criteria for classification and labelling (1272/2008)
Executive summary:

R507 -2 was administered by a single dermal application to two subsequent groups of 5 female Wistar rats and 5 male rats at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15)

No Mortality occurred.

Hunched posture, piloerection and/or chromodacryorrhoea were noted among both males and females. In addition, lethargy, flat posture, uncoordinated movements, quick breathing, shallow respiration, ptosis and/or hypothemia were noted in all males. The animals had recovered from the symptoms between Days 2 and 3.

These symptoms were occasionally seen in dermal toxicity studies. Based on their mild nature and short duration, these symptoms were considered to be of no toxicological significance.

Scales and/or scabs were seen in the treated skin area of the majority of females during the observation period.

Red staining of the treated skin area and/or other body parts of the animals was noted during the observation period and was considered to be related to staining properties of the test substance.

The changes noted in the body weight gain in males and females were within the range expected for rats used in this type of study.

At macroscopic post mortem examination, isolated grey/white foci, enlargement and dark red discoloration were found in the papillary process in the liver of one male. Macroscopic post mortem examination of the other animals at termination did not reveal any abnormalities.

The dermal LD50 value of R507-2 in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, R507-2 does not have to be classified and has no obligatory labelling requirement for dermal toxicity according to the GHS of Classification and labelling of Chemicals of the United nations (2004) and EC criteria for classification and labelling (1272/2008)