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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
June 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted study according to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Description: Red-brown liquid
Batch: 502H0003
Purity: 52.5%
Free EDTA: 2.1%
Ferrous content: 0.07%
Balance: water
Test substance storage: in refrigerator (2-8°C) protected from light
Stability under storage conditions: stable
Expiry date: 01 February 2011

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: ca. 10 weeks old
- Weight at study initiation:
- Fasting period before study: not needed
- Housing: individually (group housed during acclimation)
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.7 – 21.5
- Humidity (%): 38-75
- Air changes (per hr): ca. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From 1 to 16 June 2010

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Method: dermal application.
Clipping: one day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application: the test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.
Frequency: single dosage, on Day 1.
Dose level (volume): 2000 mg/kg body weight, dose volume calculated as dose level (g/kg) / density (g/mL).
Application period: 24 hours, after which dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 h
Doses:
2000 mg/kg w
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality twice daily, body weights on Days 1 (pre-administration), 8 and 15, clinical signs at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no
Statistics:
not required in a limit test

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
Chromodacryorrhoea was noted in two males and one female on Day 1 or 2. In two females hunched posture (Day 1) or piloerection (Day 6) were noted. Scabs were seen in the treated skin-area or in general of one male and three females during the observation period.
Body weight:
Body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination.
Other findings:
No

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The dermal LD50 was in excess of 2000 mg/kg bw
Executive summary:

The study was carried out based on the guidelines described in:

- OECD No.402 (1987) "Acute Dermal Toxicity"

- Commission Regulation (EC) No 440/2008, B3: "Acute Toxicity (Dermal)"

- EPA, OPPTS 870.1200 (1998), "Acute Dermal Toxicity"

- JMAFF Guidelines (2000), including the most recent revisions.

EDTA-Fe(NH4)NH4OH was administered to five Wistar rats of each sex by a single dermal occlusive application 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. Chromodacryorrhoea was noted in two males and one female on Day 1 or 2. In single females hunched posture (Day 1) or piloerection (Day 6) were noted. Scabs were seen in the treated skin-area of one male and three females during the observation period. Body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals. The dermal LD50 value of EDTA-Fe(NH4)NH4OH in Wistar rats was established to exceed 2000 mg/kg body weight.