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Administrative data

Description of key information

Acute oral toxicity (OECD 423, rat): LD50>2000 mg/kg bw
Acute inhalation toxicity: no data available
Acute dermal toxicity (weight of evidence):
CAS 23432-64-6 (OECD 402, rat): LD50>2000 mg/kg bw
CAS 23432-65-7 (OECD 402, rat): LD50>2000 mg/kg bw

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:
23 June - 23 July 2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 1996
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted 2001
Deviations:
yes
Remarks:
200 mg/kg bw instead of 300 mg/kg bw was used as starting dose.
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Arbeitsschutz, Arbeitsmedizin und Sicherheitstechnik, München, Germany
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: HsdBrlHan:WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: no data available
- Weight at study initiation: 143 - 154 g (step 1), 142 - 152 g (step 2), 151 - 160 g (step 3), 143 - 162 g (step 4)
- Housing: animals were kept in Macrolon cages on Altromin saw fiber bedding
- Fasting period before study: yes (overnight before dosing and 3-4 h after dosing)
- Diet: Altromin 1324 maintenance diet for rats and mice (totally-pathogen-free), ad libitum
- Water: tap water, ad libitum
- Acclimation period: yes, adequate acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 55±10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
cotton seed oil
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 5 ml/kg bw (step 1-4)

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg bw (step 1-4)
Doses:
200, 2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: a careful clinical observation was made twice a day on the day of dosing and once a day thereafter, body weights were determined prior to substance application and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical examination included changes in the skin/fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Sex:
male/female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs of toxicity were observed.
Body weight:
The weight gain was within the expected range.
Gross pathology:
Beside acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no special gross pathological changes were found in any animal.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In an acute oral toxicity study according to OECD guideline 423 and in compliance with GLP, no mortality and no clinical signs of toxicity were observed up to 2000 mg/kg bw. In conclusion, a LD50 cut-off value of 5000 mg/kg bw was derived.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

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:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
weight of evidence
Justification for type of information:
refer to analogue justification document provided in IUCLID section 13
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In acute dermal toxicity studies according to OECD guideline 402 and in compliance with GLP with two source substances methyl-N-[(trimethoxysilyl)methyl]carbamate (CAS 23432-64-6) and methyl-N-{[dimethoxy(methyl)silyl]methyl}carbamate (CAS 23432-65-7), no mortality and no clinical signs of toxicity were observed at the limit dose of 2000 mg/kg bw. Furthermore no skin reactions were observed after the 24-h treatment under occlusive conditions. In conclusion a LD50 >2000 mg/kg bw was derived. As explained in the analogue justification, the differences between the target and the source substances are unlikely to lead to differences in the dermal LD50.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2 due to read-across) and consistent studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on similarities in PC/TOX properties (refer to endpoint discussion for further details). Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

Oral

An acute oral study is available for methyl-N-[3-(trimethoxysilyl)propyl]carbamate (CAS 23432-62-4), which was conducted according to OECD 423 and in compliance with GLP (BSL Bioservice, 2002). Three male and female Wistar rats were treated with 200 or 2000 mg/kg bw by oral gavage using a stepwise procedure. The test substance was applied in cotton seed oil (total application volume 5 ml/kg). The rats were observed twice on the day of application and once daily thereafter for clinical signs and mortality. Body weights were obtained prior to treatment and on day 7 and 14. Necropsy of survivors was performed at the end of the study. No mortality was observed in the 200 and 2000 mg/kg bw dose groups in any sex. There were no changes or differences observed in body weight gains. No clinical signs of toxicity were observed in any animal at any dose level. Beside acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no special gross pathological changes were found in any animal. In conclusion a LD50 >2000 mg/kg bw was derived for male and female rats.

For assessment of the acute dermal toxicity potential of methyl-N-[3-(trimethoxysilyl)propyl]carbamate, data from 2 structural analogues were chosen in a weight of evidence approach. Refer to analogue justification document provided in IUCLID section 13.

An acute dermal toxicity study with methyl-N-[(trimethoxysilyl)methyl]carbamate(CAS 23432-64-6) is available, which was conducted according to OECD 402 and in compliance with GLP (BSL Bioservice, 2003a). Five male and female Wistar rats were treated with the limit dose of 2000 mg/kg bw by occlusive dermal application for 24 h. The test substance was applied to the back of the animals covering at least 10% of the total body surface. The application sites were washed with water after 24 h. The rats were observed twice on day of application and once daily thereafter for clinical signs and mortality, respectively. Body weights were obtained on the day of treatment and on day 7 and 14. Necropsy of survivors was performed. The application sites were also examined for signs of erythema and/or oedema. No mortality was observed and no clinical signs of toxicity were observed throughout the observation period. Weight gain of all animals was normal. Beside acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no special gross pathological changes were found in any animal. No changes of the skin at the application site were observed.

In conclusion, a LD50 of >2000 mg/kg bw was derived for male and female animals.

 

A further acute dermal toxicity study with methyl-N-{[dimethoxy(methyl)silyl]methyl}carbamate (CAS 23432-65-7) is available, which was conducted according to OECD 402 and in compliance with GLP (BSL Bioservice, 2003b). Five male and female Wistar rats were treated with the limit dose of 2000 mg/kg bw by occlusive dermal application for 24 h. The test substance was applied to the back of the animals covering at least 10% of the total body surface. The application sites were washed with water after 24 h. The rats were observed twice on day of application and once daily thereafter for clinical signs and mortality, respectively. Body weights were obtained on the day of treatment and on day 7 and 14. Necropsy of survivors was performed. The application sites were also examined for signs of erythema and/or oedema. No mortality was observed and no clinical signs of toxicity were observed throughout the observation period. Weight gain of all animals was normal. Beside acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no special gross pathological changes were found in any animal. No changes of the skin at the application site were observed.

In conclusion, a LD50 of >2000 mg/kg bw was derived for male and female animals.

Justification for classification or non-classification

The available data on acute oral toxicity of methyl-N-[3 (trimethoxysilyl)propyl]carbamate do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

Reliable data from structural analogues on acute dermal toxicity indicates that methyl-N-[3 (trimethoxysilyl)propyl]carbamate do not meet the criteria for classification according to Regulation (EC) 1272/2008, and the available data are therefore conclusive but not sufficient for classification.

No data are available for the inhalation route.