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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 May 2010 - 25 May 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
This study has been performed according to OECD and EC guidelines and according to GLP principles.

Data source

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

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
Qualifier:
according to guideline
Guideline:
other: JMAFF Guidelines (2000), including the most recent revisions.
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Test material form:
solid - liquid: aqueous solution
Details on test material:
- Physical state: Clear colourless liquid (determined at NOTOX)
- Expiration date of the lot/batch: 18 December 2010 (allocated by NOTOX, 1 year after receipt of the test substance)
- Storage condition of test material: At room temperature in the dark
- Stability under storage conditions: Stable
- Other:
Density: 1.189 kg/L at 21°C
pH: 3.0 ± 0.5% (20°C)

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 10 weeks old) were selected
- Weight at study initiation: Males: 281 - 310 gram; Females: 196 - 238 gram. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: No.
- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom). During the acclimatization period the animals were group housed in Macrolon cages (MIV type).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: Acclimatization period was at least 5 days before start of treatment under laboratory conditions.
- Health inspection: A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6 – 21.4ºC
- Humidity (%): 40 – 62%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 11 May 2010 To: 25 May 2010

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
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.

REMOVAL OF TEST SUBSTANCE
After 24 hours of application, dressings were removed and the skin cleaned of residual test substance using tap water.

TEST MATERIAL
2000 mg/kg (1.682 mL/kg) body weight. The purity of active ingredient (water free) ≥ 69.1 % (Al content 4.4%).
Dose volume calculated as dose level (g/kg) / density (g/mL).
Duration of exposure:
24 hrs
Doses:
2000 mg/kg (1.682 mL/kg) body weight. The purity of active ingredient (water free) ≥ 69.1 % (Al content 4.4%).
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days.
- Observations
Mortality/Viability: Twice daily.
Body weights: 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: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
Statistics:
Not applicable.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The purity of active ingredient (water free) ≥ 69.1 % (Al content 4.4%).
Mortality:
No mortality occurred.
Clinical signs:
Two females showed chromodacryorrhoea (snout) and one male showed piloerection on Day 1.
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.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, 202028/A (purity of active ingredient (water free) ≥ 69.1 %; Al content 4.4%) is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the estimated dermal LD50 is higher than 2000 mg/kg bw and as no toxicological effects is expected between 2000 and 5000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study (limit test) performed according to the OECD guideline No 402 and in compliance with GLP, a group of Wistar rats (5/sex) were given a single dermal application of 202028/A at 2000 mg/kg bw. The test substance 202028/A (purity of active ingredient (water free) ≥ 69.1 %; Al content 4.4%) was applied topically to the shaved skin area of the animals and covered with occlusive binding for 24h. After the exposure period, the dressing was removed and the skin was cleaned of residual test substance using tap water.

Animals were observed for toxicity, clinical signs and body weight for 15 days and then necropsied for macroscopic observations.

 

No mortality occured.

Two females showed chromodacryorrhoa (snout) and one male showed piloerection on Day 1.

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.

No macroscopic abnormalities were found during the necropsy.

 

Dermal LD50 rabbit > 2000 mg/kg bw

 

Under the test conditions, 202028/A (purity of active ingredient (water free) ≥ 69.1 %; Al content 4.4%) is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as the estimated dermal LD50 is higher than 2000 mg/kg bw and as no toxicological effects is expected between 2000 and 5000 mg/kg bw.

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