Carbamic acid, N-[(dimethoxymethylsilyl)methyl]-, methyl ester

Endpoint summary

Description of key information

Oral (OECD 423): LD50 cut-off = 5000 mg/kg bw
Inhalation: no data available 
Dermal (OECD 402): 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 Jun - 17 Jul 2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

No information of analytical purity of the test material is provided.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

(1996)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(1996)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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 or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Weight at study initiation: Step 1: 134 – 158 g (males), Step 2: 126 – 158 g (females), Step 3: 148 – 160 g (males), Step 4: 145 – 150 g (females)
- Fasting period before study: Animals were fasted by withholding food overnight and for a further 3 – 4 h after dosing.
- Housing: Animals were caged in macrolon cages on Altromin saw fiber bedding.
- Diet: Altromin 1324 maintenance diet for rats and mice, ad libitum
- Water: (tap/filtered) water, ad libitum
- Acclimation period: adequate 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
- Justification for choice of vehicle: The vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no.: 21K0162

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

DOSAGE PREPARATION: The test substance was freshly mixed prior to application and stirred throughout dose administration to guarantee stability and homogeneity.

CLASS METHOD:
- Rationale for the selection of the starting dose: The starting dose was chosen according to OECD TG 423.

Doses:

200 mg/kg bw
Step 1: 3 males
Step 2: 3 females

2000 mg/kg bw
Step 3: 3 males
Step 4: 3 females

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 weighing: The animals were weighed prior to first application and once a week thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical examination was made twice a day on the day of dosing and once a day thereafter.

Key result

Sex:

male/female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

There was no mortality observed throughout the study period.

Clinical signs:

other: No clinical signs of toxicity were observed throughout the observation period.

Gross pathology:

No special gross pathological changes were found in all animals.

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

In this acute toxic class method three fasted Wistar rats of each sex were administered one dose of 200 or 2000 mg/kg bw of the test substance (CAS 23432-65-7) in a stepwise procedure via oral gavage. The animals were observed for 14 days after administration. The acute oral LD50 cut-off value for males/females was calculated to be 5000 mg/kg bw. No signs of clinical toxicity and no mortalities occurred during the observation period. All animals showed the expected body weight gains over the study period. No treatment related gross necropsy findings were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study, 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:

experimental study

Adequacy of study:

key study

Study period:

18 Aug - 11 Sep 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted in 1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Arbeitsschutz, Arbeitsmedizin und Sicherheitstechnik, München, Germany

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: no data
- Weight at study initiation: 210 - 221 g (male), 198 - 208 g (female)
- Fasting period before study: no
- Housing: animals were barrier maintained (semi-barrier) in Macrolon Cages on Altromin saw fiber bedding
- Diet: Altromin 1324 maintenance diet for rats and mice (totally pathogen-free), ad libitum
- Water: tap water, ad libitum
- Acclimation period: adequate acclimatisation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- % coverage: not less than 10% of body surface
- Type of wrap if used: test item was held in contact with the skin with a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner

REMOVAL OF TEST SUBSTANCE
- Washing: residual test item was removed by using water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 2000 mg/kg bw

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

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 examination was made twice on the day of dosing and once daily thereafter, weighing was performed prior to application and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical examination included changes in the skin/fur, oedema and erythema, 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.

Key result

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

Mortality:

No mortality was observed during the study period.

Clinical signs:

other: No clinical signs of toxicity were observed throughout the observation period.

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.

Other findings:

No changes of the skin at the application site were observed.

Table 1: Weight gain [g] of the animals in the acute dermal toxicity study.

Animal No.	Sex	Day 0	Day 7	Day 14
1	male	218	249	293
2	male	220	252	298
3	male	210	243	286
4	male	221	246	291
5	male	213	232	260
6	female	202	186	189
7	female	208	217	229
8	female	201	204	211
9	female	205	209	233
10	female	198	200	212

 

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008

Conclusions:

In an acute dermal toxicity study according to OECD guideline 402 and in compliance with GLP, 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Acute oral toxicity

A key acute oral toxicity study with methyl-N-{[dimethoxy(methyl)silyl]methyl}carbamate (CAS 23432-65-7) is available and was performed according to OECD TG 423 and in compliance with GLP (BSL, 2002). In this acute toxic class method three fasted Wistar rats of each sex were administered one dose of 200 or 2000 mg/kg bw of the test substance (CAS 23432-65-7) in a stepwise procedure via oral gavage. The animals were observed for 14 days after administration. The acute oral LD50 cut-off value for males/females was calculated to be 5000 mg/kg bw. No signs of clinical toxicity and no mortalities occurred during the observation period. All animals showed the expected body weight gains over the study period. No treatment related gross necropsy findings were observed. Based on the study results and according to EU classification criteria, the test substance is not to be classified.

Acute dermal toxicity

A key acute dermal toxicity study performed according to OECD TG 402 and in compliance with GLP with methyl-N-{[dimethoxy(methyl)silyl]methyl}carbamate (CAS 23432-65-7) is available (BSL, 2003). In this limit test five Wistar rats of each sex were exposed to 2000 mg/kg bw of the test substance for 24 h via occlusive dressing and observed for 14 days post-application. The acute dermal LD50 value for males/females was calculated to be greater than 2000 mg/kg bw. No signs of clinical toxicity were reported and no mortalities occurred during the observation period. No remarkable changes or differences in body weights were recorded. No treatment related gross necropsy findings were observed. Based on the study results and according to EU classification criteria, the test substance is not to be classified.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification. No data are available for the inhalation route.