Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): methoxy-3-propylamine
- Batch:, 26/05/92
- Purity: 99.44%
- Supplier: Elf Atochem, La Chambre

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: lffa Crédo, 69210 L'Arbresle, France
- Age on the day of treatment: 8 weeks old
- Weight on the day of treatment: 282 ± 10 g for the males and 229 ± 8 g for the females.
- Fasting period before study: no
- Housing: individually during the study In polycarbona te cages
- Diet: ad libitum with a certified pelleted diet "Rats- Mice sustenance ref. A04 C" (U.A.R., 91360 Villemoissonsur/Orge, France)
- Water: free access to tap water filtered by a 0.22 micron filter membrane
- Acclimation period: at !east 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): The air was non-recycled and filtered
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
The test substance in its original form was applied at a dose level of 2000 mg/kg at a volume of 2. 30 ml/kg taking into consideration that the specifie gravity (SG) of the test substance was 0.871 directly to the skin. The test substance in water for injections at a dose level of 400 mg/kg at a volume of 5 ml/kg was prepared on a dry hydrophilic gauze patch ) and then applied to an area of skin representing approximately 10% (5 x 6 cm for the females and 5 x 7 cm for the males) of the body surface of the animal. This was calculated according to Meeh' s formula. The test substance and the gauze patch were held in contact with the skin for 24 hours by means of an adhesive hypoallergic aerated semi-occlusive dressing attached to a restraining bandage. This dressing prevented the ingestion of the test substance by the animal. No residual test substance was observed at removal of the dressing.
Duration of exposure:
24 hours
Doses:
2000 and 400 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The animals were checked for clinical signs, mortality and body weight gain for a period of 4 days (2000 mg/kg) or 14 days (400 mg/kg) after the single application of the test substance. A necropsy was performed on each animal sacrificed at the end of the study.
Statistics:
None

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 2 000 mg/kg bw
Mortality:
At 400 mg/kg, no deaths occurred during the observation period.
At 2000 mg/kg, 4 females died between days 2 and 4.
Clinical signs:
At 400 mg/kg, no clinical signs were observed during the study.
At 2000 mg/kg, sedation or hypokinesia and dyspnea were noted between days 2 and 5. Signs of necrosis and ulceration were also observed after removal of the dressing.
Body weight:
At 400 mg/kg, the body weight gain of the animals was normal.
Gross pathology:
In all animals treated wi th the 400 mg/kg dose level, the macroscopic examination of the main organs of the animals sacrificed at the end of the
study revealed no apparent abnormalities.
In all animals treated wi th the 2000 mg/kg dose level, samples of skin were taken. Nec rosis of the skin (male Nos. 01, 03, 04, 05; female Nos. 01, 02, 03, 04, 05) and signs of ulceration affected of the whole depth skin (male No. 02) were observed at necropsy.
No histological examination was performed on cutaneous samples.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the test substance methoxy-3-propylamine when administered by dermal route in rats was higher than 400 mg/kg. No signs of toxicity were observed at this dose level. The LD50 was estimated at 2000 mg/kg.
In order to comply with new ethic and scientific recommendations concerning the LD50, a more precise determination was not necessary.
Executive summary:

The acute toxicity of the test substance methoxy-3 -propylamine was evaluated in rats according to the recommendations of the OECD Guideline No. 402 (OECD, 24th February 1987) for the testing of chemicals administered by dermal route and the Principles of Good Laboratory Practice (OECD, 12th May 1981). In a first assay, the test substance was applied in its original form directly to the skin of 10 Sprague-Dawley rats (5 males and 5 females) at a dose level of 2000 mg/kg, at a volume taking into consideration that the specific gravity (SG) of the test substance was 0.871. In a second assay, the test substance was solubilised in water, prepared on a dry compress at a dose level of 400 mg/kg and then applied to the skin of 10 SpragueDawley rats {5 males and 5 females) at a volume of 5 ml/kg. After 24 hours under a semi-occlusive dressing, no residual test substance was observed at removal of the dressing. The animals were checked for clinical signs, mortality and body weight gain for a period of 4 days (2000 mg/kg) or 14 days (400 mg/kg) after the single application of the test substance. A necropsy was performed on each animal sacrificed at the end of the study. At 400 mg/kg, the general behaviour and body weight gain of the animals were not affected by the treatment. No deaths occurred at the dose level of 400 mg/kg. The macroscopic examination revealed no abnormalities in the animals sacrificed at the end of the study. At 2000 mg/kg, 4 females died between days 2 and 4. Cutaneous signs of necrosis and ulceration appeared between days 2 and 5. The animals were sacrificed for humane reasons on day 5. Under these experimental conditions, the LD50 of the test substance when administered by dermal route in rats was higher than 400 mg/kg. No signs of toxicity were observed at this dose level. The LD50 was estimated at 2000 mg/kg. In order to comply with ethic and scientific recommendations concerning the LD50, a more precise determination was not necessary.