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Description of key information

In the key acute oral study, conducted according to OECD Test Guideline 401 and in compliance with GLP (Hüls, 1993a), the LD50 (rat) value was concluded to be > 2000 mg/kg bw (limit test). Clinical signs observed after dosing were abnormal gait, squatting, staggering, salivation and lacrimation, hypothermia, and uncontrolled movements. These had fully resolved by the 24-hour observation. No abnormalities were detected at necropsy.

No acute inhalation data are available which meet current guideline requirements. However, supporting studies in which rats were exposed to substantially saturated vapour for 6-8 hours showed no mortality, indicating a low potential for acute inhalation toxicity.

In the key acute dermal study, conducted according to OECD Test Guideline 402 and in compliance with GLP (Hüls, 1993b), the LD50 (rat) value was concluded to be > 2000 mg/kg bw (limit test). There were no clinical signs or necropsy findings.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-05-17 - 1993-06-08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: BOR:WISW (SPF Cpb)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Harlan Winkelmann GmbH, 33176 Borchen, Gartenstr. 27

- Age at study initiation: 6 - 8 weeks

- Weight at study initiation: 131-180 g

- Fasting period before study: 16 hours before commencement of study.

-Housing: Conventional, maximum of 5 animals/cage

- Diet: Ssniff R 10 Comprehensive diet for rats (ad libitum)

- Water: ad libitum

- Acclimation period: minimum of 5 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 20°C ± 3°C

- Humidity (%): 30-70%

- Air changes (per hr): 15

- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: Not stated
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.85 cm3/kg

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex/group (2 of each sex in preliminary study and 3 of each sex in actual study. The final results include all animals.)
Control animals:
not specified
Details on study design:
A group of ten (5 male and 5 female) rats was given a single oral dose of undiluted test substance at a dose level of 2000 mg/kg bw. Animals were observed 1 and 4 hours after dosing and then once a day for 14 days. Bodyweights were recorded on the day of treatment and on days 7 and 14. All animals were subject to gross necropsy examination for any macroscopic abnormalities.
Statistics:
Not applicable.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities in response to the exposure.
Clinical signs:
Up to six hours after administration clinical signs of toxicity were noted including abnormal gait, squatting, staggering, salivation and lacrimation, hypothermia, and uncontrolled movements. All animals appeared normal by the 24 hour observation point.
Body weight:
Weight gain of ca. 40-80 g between day 0 and day 14 was evident in all animals.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
An acute oral LD50 (rat) >2000 mg/kg was determined in a reliable study conducted in accordance with the now deleted OECD 401 test guideline and in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993/05/17-1993/06/08
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Bor:WISW (SPF Cpb)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS

- Source: Harlan Winkelman GmbH, 33176 Borchen, Gartenstr. 27

- Weight at study initiation: 200-300g

- Housing: The animals were individually caged in Type 3 Makrolon cages

- Diet: Ssnif R 10 Comprehensive diet for rats (ad libitum), Ssniff Specialfoods GmbH, 59494 Soest

- Water: ad libitum

- Acclimation period: minimum of 5 days


ENVIRONMENTAL CONDITIONS

- Temperature (°C): 20°C ± 3°C

- Humidity (%): 30-70

- Air changes (per hr): 15

- Photoperiod (hrs dark / hrs light): 12h/12h


Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE

- Area of exposure: the back

- Type of wrap if used: the area was covered and an acrylic bandage used as wrap and attached to the skin with plaster strips.

REMOVAL OF TEST SUBSTANCE

- Washing (if done): with warm water

- Time after start of exposure: 24h


TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 1.85 cm3/kg


Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex/group
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were observed 30 minutes, 1,2,3,4,5 and 6 hours post application and daily for the 14 hour observation period. The animals were weighed at day 0, 7 and 14.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: All animals were subject to gross necropsy examination for any macroscopic abnormalities.
Statistics:
No statistical analysis of the results was deemed necessary.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities in response to application of the test substance at 2000 mg/kg bw.
Clinical signs:
There was no evidence of systemic toxicity noted during the study period
Body weight:
All animals showed normal gains in body weight over the study period
Gross pathology:
There were no abnormalities noted at necropsy.
Other findings:
- Other observations: The sections and macroscopic examinations of the animals revealed no evidence of compound related changes in any organs.

There were no visible changes in the application area in the 14 day exposure period. There were no mortalities in response to the exposure to the test substance.

Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 value of >2000 mg/kg bw was determined in a reliable study conducted according to an appropriate test protocol, and in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

In the key acute oral study with (3-chloropropyl)trimethoxysilane, conducted according to the now-deleted OECD Test Guideline 401 (limit test) and in compliance with GLP (Hüls, 1993a), the concluded LD50 (rat) value was >2000 mg/kg bw. In the study, a group of ten (5 male and 5 female) rats was given a single oral dose of undiluted test substance at a dose level of 2000 mg/kg bw. The animals were observed at 1 and 4 hours after dosing and then once a day for 14 days. Bodyweights were recorded on the day of treatment and on days 7 and 14. All animals were subject to gross necropsy examination for any macroscopic abnormalities.

No mortality occurred during the study period. Up to six hours after administration clinical signs of toxicity were noted which included abnormal gait, squatting, staggering, salivation and lacrimation, hypothermia, and uncontrolled movements. All animals appeared normal by the 24-hour observation point. The expected body weight gain was observed during the study period. No macroscopic abnormalities were observed at necropsy.

Three older studies support this conclusion, although much higher dose levels were tested than required by current guidelines (BRRC 1990; Carnegie-Mellon 1974; Dow Corning Corporation, 1982).

In the key acute dermal toxicity study, conducted according to OECD Test Guideline 402 and in compliance with GLP (Hüls, 1993b), the LD50 (rat) value was concluded to be > 2000 mg/kg bw (limit test). In the study, 2000 mg/kg bw of undiluted (3-chloropropyl)trimethoxysilane were applied topically onto the skin of 5 male and 5 female rats for 24 hours under semi-occlusive dressing. The animals were observed at 30 minutes, 1, 2, 3, 4, 5 and 6 hours post-application and daily for 14 days thereafter. The animals were weighed on study days 0, 7 and 14. All the animals were subject to necropsy at the end of the 14-day observation period.

No mortality occurred during the study period. During the study period, there was no evidence of systemic toxicity noted during the study period and expected body weight gain was observed during the study period. No macroscopic abnormalities were observed at necropsy.

The findings of the key study are supporting by another two older studies (BRRC 1990; Carnegie-Mellon 1974).

No reliable acute inhalation data are available.

Justification for classification or non-classification

Based on the available information, (3-chloropropyl)trimethoxysilane is not classified for acute toxicity according to Regulation (EC) No 1272/2008.

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