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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 May 1989 until 02 February 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1990

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
N,N',N''-tricyclohexyl-1-methylsilanetriamine
EC Number:
240-040-8
EC Name:
N,N',N''-tricyclohexyl-1-methylsilanetriamine
Cas Number:
15901-40-3
Molecular formula:
C19H39N3Si
IUPAC Name:
N,N',N''-tricyclohexyl-1-methylsilanetriamine
Test material form:
liquid: viscous

Test animals

Species:
rat
Strain:
other: Sprague-Dawley ( Ico rat - OFA.SD ). IOPS Caw.
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Iffra-Credo, France
- Age at study initiation: between 6 and 8 weeks old
- Weight at study initiation: from 206 g to 259 g
- Fasting period before study: no
- Housing: housed individually in type FI polycarbonate cages
- Diet: complete pelled rat-mouse maintenance died ad libitum
- Water: softened and filtered mains drinking water ad libitum
- Acclimation period: 7 days before the start of the treatment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 44 to 90% R.H.
- Air changes (per hr): at least 10 per hour
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: the trunk
- % coverage: 10% of the total body surface area
- Type of wrap if used: semi-occlusive dressing (perforated adhesive band and elastic bandage)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Constant volume or concentration used: no.


Duration of exposure:
24 hours
Doses:
Four groups of 5 males and 5 non-pregnant females were treated with 1594mg/kg, 2006 mg/kg, 2515 mg/kg and 1267 mg/kg respectively.
No. of animals per sex per dose:
5 males and 5 non-pregnant females
Control animals:
yes
Details on study design:
Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weight observation prior to the treatment, at days 8 and 15
- Necropsy of survivors performed: yes. At day 15 al surviving rats were killed my means of overdosing with carbon dioxide. Particular attention was paid to liver, heart, kindneys and lungs.
- Other examinations performed: any deaths and clinical observations were noted at 15 minutes after administration, then at 1,2 and 4 hours, and
then daily for 14 days after administration with detaled description of the clinical signs. The daily observations included changes in the fur, in the
treated skin, the eyes, mucous membranes, respiratory system, circulatory syste, autonomic and central nervous system as well as somato-motor
activity and behaviour.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 594 mg/kg bw
Based on:
test mat.
Mortality:
Mortality was observed in 10% from the female group treated with 1267 mg/kg from day 4 onwards, in 50% from the female group treated with
1594 mg/kg from day 2 onwards, in 90% from both female and male group treated with 2006 mg/kg from dat 2 onwardsand in 100% in the
female and male group treated with 2515 mg/kg from day 2 onwards.
Clinical signs:
Prostration or lethargy was observed in all the animal groups on day 2 from the study. On day 3 rats treated with 1267 mg/kg and 1594 mg/kg had
normal behaviour. One female from the group treated with 2006 mg/kg was presenting with lethargy at days 3 and 4 and one male from the same
group was presenting with prostration on day 3. On day 5 all the surviving rats had norml behaviour.
Body weight:
Body weight changes in group 2-5 males were identical to the those in the control group. The body weigh changes of females from group 5 were
signifiantly lower to those of the control group.
Gross pathology:
The macroscopic abnormalities observed were characterized by congestive aspect of the lungs of the cutaneous and sub-cutaneous tissues in the
animals dead during the study and by an oedema of the sub-cutaneous tissues in the animals killed at the end of the study as well as purple colour of
the tissue in the group treated with 2515 mg/kg.
Other findings:
Epidermal necrosis was observed in all the animals. Dryness of the skin in groups 2-3 on days 2 to 3, and in group 5 on days 2 to 4. Superficial
eschar formations were observed in groups 2-3 from day 4 and group 5 from day 5 until day 15 from the study.

Any other information on results incl. tables

The estimated values of LD50for males and females separately are:

1594 mg/kg < LD50 by the cutaneous route, in the male rat < 2006 mg/kg

1267 mg/kg < LD50 by the cutaneous route, in the female rat < 1594 mg/kg.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 was reported to be 1594 mg/kg bw in a reliable study, conducted according to OECD guideline and in compliance with GLP.