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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:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Credo, 69210 L'Arbresle, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 281+/-4g (males) and 226+/-8g (females)
- Fasting period before study: no
- Housing: per grouop of 4 to 7 during acclimatization and individually during the study period
- Diet: ad libitum with certified pelleted diet "Rats - Mice sustenance ref. AO4 C " (U.A.R.; 91360 Villemoisson-sur-Orge, France)
- Water: ad libitum with tap water filtered by a 0.22µ filter membrane (Société Millipore, 78140 Vélizy, France)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 50+/-20
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12:12


IN-LIFE DATES: From: 15 Oct 1992 (D1) To: 29 Oct 1992 (necropsy)

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: 5x6 cm (females) and 5x7 (males)
- % coverage: approx. 10 %
- Type of wrap if used: hydrophilic gauze patch (Semes France, 54183 Heillecourt, France) maintained by an adhesive hypoallergenic aerated semi-occlusive dressing (Laboratoires de Pansements et d'Hygiène, 21300 Chenôve, France) attached to a restraining bandage (Laboratoires 3M Santé, 92245 Malakoff, France)

REMOVAL OF THE SUBSTANCE: no

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): a volume of 5 ml/kg
- Constant volume used: yes
Duration of exposure:
24 hours
Doses:
400 mg/kg (main study), 1000 and 2000 mg/kg (preliminary study)
No. of animals per sex per dose:
5 males and 5 females (main study), 1 males and 1 female (preliminary study)
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days (5 days for preliminary study)
- Frequency of observations and weighing: Animals were observed 15, 30 hours, 1, 2, 4 hours after treatement, then once daily during 14 days. Animals were weighted before application of DMAPA and then on days 5, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, cutaneous examination, macroscopic examination of the main organ (digestive tract, heart, kidneys, liver, lings, pancreas, spleen, and any organ with obvious abnormalities.

Results and discussion

Preliminary study:
At 2000 mg/kg, both animals (one male and one female) died on day 2. They showed no clinical signs before death.
At 1000 mg/kg, both animals showed sedation and tremors between D2 and D5 with severe cutaneous reactions (necrosis associated with oedema on D2).
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 400 - < 2 000 mg/kg bw
Mortality:
At 400 mg/kg, no mortality was observed during the observation period.
Clinical signs:
At 400 mg/kg, no clinical signs were observed. No irritation was observed.
Body weight:
The body weight gain of treated animals was normal.
Gross pathology:
The macroscopic examination of the main organs of the animais sacrificed at the end of the study revealed no apparent abnormalities.
Due to the absence of macroscopic lesions, no samples were taken for histological examinations.

Any other information on results incl. tables

Preliminary Study
Dose (mg/kg) Animals Time Clinical signs Time Cutaneous reactions
1000 Male 01 30 min None D2 Necrosis, oedema
2 hours None D3 to D5 Necrosis
4 hours None  
D2 to D5 Sedation, tremors    
Female 01 30 min None D2 Necrosis, oedema
2 hours None D3 to D5 Necrosis
4 hours None  
D2 to D5 Sedation, tremors    
2000 Female 02 30 min None    
2 hours None  
4 hours None  
D2 Death    
Female 02 30 min None    
2 hours None  
4 hours None  
D2 Death    

Main Study
Dose (mg/kg) Animals Time Clinical signs
400 all (5 males and 5 females) 15 min None
30 min None
1 hour None
2 hours None
4 hours None
D2 to D15 None

Both animals died on day 2 after administration of 2000 mg/kg (1 male and 1 female). They showed no clinical signs before death.

After administration of 1000 mg/kg, both rats showed sedation and tremors between D2 and D5 with severe cutaneous reactions (necrosis associated with oedema on D2).

At 400 mg/kg, animals showed no clinical signs nor irritation.

Under these experimental conditions, the dermal LD50 of DMAPA is between 400 mg/kg and 2000 mg/kg in rats.

Applicant's summary and conclusion