Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP 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)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): n-HEPTYLAMINE
- Physical state: clear liquid
- Analytical purity: 99.58%
- Lot/batch No.: 10/07/92

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Crédo, 69210 L'Arbresle, France
- Age at study initiation: approximately 8 weeks old
- Weight at study initiation: mean body weight of 279 ± 10 g for the males and 225 ± 2 g for the females
- Fasting period before study: no
- Housing: The animals were housed in groups of 4 to 7 animals of the same sex per cage during the acclimatization period and individually during the study. They were housed in polycarbona te cages ( 48 x 27 x 20 cm) during the acclimatization period, and (35.5 x 23.5 x 19.3 cm) throughout the study.
- Diet: fed ad libitum with a certified pelleted diet "Rats - Mice sustenance ref. A04 C"
- Water: free access to tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 50 ± 20%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 x 6 cm for the females and 5 x 7 cm for the males
- % coverage: 10% of the body surface of the animals.
- Type of wrap if used: restraining bandage (Laboratoires 3M Santé, 92245 Malakoff, France)

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.5ml/kg


Duration of exposure:
Single
Doses:
2000mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs: The animals were observed frequently after application of the test substance and at least once a day for 14 days in order to determine the reversibility or irreversibility of any clinical signs.
Mortality: The animals were checked frequently for mortality and signs of morbidity just after administration of the test substance and at least twice a day during the 14-day observation period.
Body weight: The animals were weighed individually just before application of the test substance and then on days 5, 8 and 15. The body weight gain of the treated animals was compared to a reference curve of C.I.T. control animals with the same initial weight.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the observation period.
Clinical signs:
No clinical signs were observed during the study.
Between days 2 and 15, signs of necrosis of the skin without tissular lesions on the whole depth of the skin were observed on the area receiving the test substance.
Body weight:
Between days 1 and 5, a decrease in the body weight of 4 males and 1 female (No. 05) was noted without subsequent consequence. The variations
in body weight recorded within the days following treatment were probably due to the severe cutaneous reactions. The body weight gain of the other
animals was normal.
Gross pathology:
No apparent abnormalities. Signs of necrosis due to the application of the test substance were observed at the application site of all animals.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Under the experimental conditions, the dermal LD0 of the test substance n-HEPTYLAMINE was higher than 2000 mg/kg.
Executive summary:

The potential acute toxicity of the test substance n-HEPTYLAMINE was evaluated in rats according to the recommendations of the O.E.C.D. Guideline No. 402 (O.E.C.D., 24th February 1987) administered by dermal route and the Principles of Good Laboratory Practice (O.E.C.D., 12th May 1981) . 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, taking into consideration that the specific gravity (SG) of the test substance was 0.773. 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 14 days after the single application of the test substance. A necropsy was performed on each animal sacrificed at the end of the study. No clinical signs were observed after application of the test substance. Between days 2 and 15, signs of necrosis of the skin without tissular lesions on the whole depth of the skin were observed on the area receiving the test substance. Between days 2 and 5, the body weight gain of the females slowed down and that of the males was reduced by 5 g. The body weight gain of all animals returned to normal thereafter. No deaths occurred at the dose level of 2000 mg/kg. Under our experimental conditions, the LD0 of the test substance n-HEPTYLAMINE when administered by dermal route in rats was higher than 2000 ng/kg.