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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:
supporting study
Study period:
April-June 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed in accordance with OECD/EC guidelines and GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
3 animals instead of 5 animals (as required by the guidelines) were used at 200 and 2000 mg/kg bw and at the discriminating level for classification 5 animals/sex were used
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
yes
Remarks:
idem
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
idem
Qualifier:
according to
Guideline:
other: JMAFF, 12 Nohsan, Notification no 8147, November 2000, including the most recent partial revisions
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: 2.5% aqueous solution
Details on test material:
- Name of test material (as cited in study report): TMA248WA
- Physical state: clear colourless liquid
- Analytical purity: 2.5% (solution in water)
- Lot/batch No.: 05C14001B
- Expiration date of the lot/batch: 13 February 2007
- Storage condition of test material: at room temperature in the dark
- pH 13.21 (determined at test lab)

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: young adults (approx. 9-12 weeks old)
- Weight at study initiation: 344-366 g for males; 184-294 g for females; one female at 1000 mg/kg bw exceeded the +/- 20% sex mean body weight range, but this is not considered to have influenced the study results
- Housing: individually housed in Macrolon cages containing purified sawdust as bedding material and paper as cage enrichment
- Diet: free access to standard pelleted laboratory animal diet (Altromin (code VRF 1), Lage, Germany)
- Water: free access to tap-water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6-22.7
- Humidity (%): 27-73; deviations from the minimum level of humidity occurred; based on laboratory historical data these deviations were considered not to have affected the study results
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 25 cm2 for males and 18 cm2 for females
- % coverage: 10
- Type of wrap if used: surgical gauze covered with aluminium foil and Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing: with water
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 200, 1000 or 2000 mg/kg bw
- Constant concentration used: yes
Duration of exposure:
24 hours
Doses:
200, 1000 and 2000 mg/kg bw; initially 3 females were treated at 200 mg/kg bw. In a stepwise procedure 3 females were dosed at 1000 and 2000 mg/kg bw and 2 females and 5 males at 1000 mg/kg bw to complete the set of animals at the highest possible dose. The test was performed with less animals combining the procedures from the acute oral toxic class method and OECD 402, which is considered not to have affected the integrity of the study.
No. of animals per sex per dose:
3 females at 200 and 2000 mg/kg bw; 5/sex at 1000 mg/kg bw
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days

OBSERVATIONS
- Mortality/viability: twice daily
- Clinical signs: at periodic intervals on day of dosing and once daily thereafter
- Body weight: pre-administration (day 1), day 8 and 15
- Necropsy of survivors performed: yes, all animals
Statistics:
Not applicable

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 000 - 2 000 mg/kg bw
Based on:
dissolved
Remarks:
(2.5% aqueous solution)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
25 - 50 mg/kg bw
Based on:
other: (pure substance)
Mortality:
2000 mg/kg bw: all three animals died/were sacrificed
1000 and 200 mg/kg bw: no mortality observed
Clinical signs:
200 mg/kg bw: flat posture and chromodacryorrhoea
1000 mg/kg bw: chromodacryorrhoea
2000 mg/kg bw: restless behaviour, clonic spasms, hunched posture, uncoordinated movements, laboured respiration in one animal; hunched posture in another animal
The surviving animals had recovered from the symptoms by day 2 or 3
Scales, scabs and /or erythema maculate were noted in the treated skin area of several animals between days 3 and 10
Body weight:
No effect on body weight was noted.
Gross pathology:
No abnormalities were found at macroscopic examination of all animals.

Applicant's summary and conclusion

Interpretation of results:
very toxic
Remarks:
Migrated information category 1 Criteria used for interpretation of results: EU
Conclusions:
The dermal LD50 of TMA248WA in Wistar rats was established to be in the range of 1000-2000 mg/kg bw, which is equivalent to 25 - 50 mg/kg bw for the pure substance.
According to EC Regulation 1272/2008 the pure substance should be classified in category 1.
Executive summary:

In an acute dermal toxicity study with TMA248WA performed according to OECD 402, the three animals exposed to 2000 mg/kg bw died/were sacrificed. At 200 and 1000 mg/kg bw no mortality occurred. Clinical signs observed at 2000 mg/kg bw included restless behaviour, clonic spasms, hunched posture, uncoordinated movements and laboured respiration. At 1000 and 200 mg/kg bw flat posture and/or chromodacryorrhoea were seen. No abnormalities were observed at macroscopic examination.

The dermal LD50 of TMA248WA in Wistar rats was established to be in the range of 1000-2000 mg/kg bw, which is equivalent to 25 - 50 mg/kg bw for the pure substance.

According to EC Regulation 1272/2008 the pure substance is classified in category 1.