A mixture of: propan-2-one-O,O'-(methoxymethylsilandiyl)dioxime; propan-2-one-O-(dimethoxymethylsilyl)oxime; propan-2-one-O,O',O''-(methylsilantriyl)trioxime

Endpoint summary

Description of key information

Acute oral toxicity: OECD Guideline 423 and GLP. LD50 value of test article Wasox-MMAC2 in rats by dermal route at 24 h exposure period is higher than 2000 mg/kg bw.

Acute dermal toxicity: OECD Guideline 402 and GLP. LD50 value of test article Wasox-MMAC2 in rats by dermal route at 24 h exposure period is higher than 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:

From September 28, 2004 to October 13, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to OECD 423 Guideline , with GLP.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Crl:CD(SD)IGS BR

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, 0-97633 Sulzfeld
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: 182 - 194 g
- Fasting period before study: The feed was withdrawn the evening before the administration of the test substance and was offered again about three hours afterwards.
- Housing: Single caging in Makroion cages type 111(39 cm x 23 cm bottom area, 18 cm height). Wire mesh lids. Bedding material: aspen wood chips.
- Diet (e.g. ad libitum): ad libitum (altromin 1324 forte)
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 22 ºC (continuous control and recording)
- Humidity (%): average 56.1% (continuous control and recording)
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): artificial light from 6 a.m. to 6 p.m.

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

(Mazola, approx. 0.02% H2O)

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: the test substance was not soluble in water. Corn oil is a common vehicle for acute oral toxicity testing
- Dose volume: 10 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: From comparable chemical substances, a minor acute toxicity is known; therefore it seemed appropriate to perform the limit test with the dose 2000 mg per kg body weight.

Doses:

2000 mg/kg body weight.

No. of animals per sex per dose:

6 females per dose (3 per step)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations: within the periods 0 - 0.5,0.5 - 1, 1 - 2,2 - 4 and 4 - 6 hours after administration (p.a.) of the test substance and then at least once a day for a total of 2 weeks.
Body weights: before administration, 7 and 14 days after administration.
- Necropsy of survivors performed: yes.
- Other examinations performed:
Clinical signs: skin, fur, eyes, occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.
Body weight: body weight gain for each week of the study (0-7 days, 7-14 days).
Gross pathology.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the scheduled termination of the study.

Clinical signs:

other: All animals were normal during the entire observation period.

Gross pathology:

Effects on organs: No relevant findings at post mortem examination were noted.

Synopsis of the results.

Dose	Step No.	Animal	Number of animals
(mg/kg)		Nos.	exposed	affected	deceased
2000	1	21, 22, 23	3	0	0
2000	2	24, 25, 26	3	0	0

Interpretation of results:

other: Not classified (CLP Regulation EC no. 1272/2008)

Conclusions:

The oral LD50 of the test article Wasox-MMAC2 in rats was higher than 2000 mg/kg bw.

Executive summary:

The Acute Toxic Class Method assay (Limit Test) for the test substance was performed in rats according to OECD 423 Guideline. Two groups of three fasted female rats was treated sequentially with a single oral dose of 2000 mg/kg body weight. The test material was administrated orally (by gavage) as an emulsion in corn oil. Clinical signs and body weights were monitored for 14 days after administration and all animals were subjected to gross necropsy. All animals survived until the scheduled termination. All animals gained weight in both weeks after administration and all were normal during the entire observation period. All animals were normal at the necropsy.

The oral LD50 of the test article Wasox-MMAC2 in rats was higher than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The study is GLP compliant and has Klimisch score = 1.

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:

From September 28 to October 12, 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

According to OECD 402 Guideline, with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CRL:CD (SD) BR SPF

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiqa, 0-97633 Sulzfeld.
- Age at study initiation: approximately 8 weeks (males) and 12 weeks (females)
- Weight at study initiation: 246-260g (males) and 232-240 g (females)
- Housing: Single caging in Makroion cages type 111(39 cm x 23 cm x 18 cm). Wire mesh lids. Bedding material: aspen wood chips.
- Diet (e.g. ad libitum): ad libitum (Altromin 1324 forte)
- Water (e.g. ad libitum): ad libitum (tap water)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average 22 ºC (continuous control and recording).
- Humidity (%): average 56% (continuous control and recording).
- Air changes (per hr): 12 per hour
- Photoperiod (hrs dark / hrs light): artificial light from 6 a.m. to 6 p.m.

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: an area of 6.5 cm x 8 cm (52 cm2) on the dorsal thoracal region
- % coverage: at least 10% of the estimated body surface.
- Type of wrap if used: A cellulose patch with the test substance was applied and held in place by fixing marginally with non irritating tape and covered semi-occlusively by a dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was wiped off using wet cellulose tissue, if necessary.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex and per dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations: within the periods 0-0.5, >0.5-1, >1-2, >2-4 and >4-6 hours after administration of the test substance and then at least once a day for a total of 2 weeks.
Body weights: before administration, 7 and 14 days after administration.
- Necropsy of survivors performed: yes.
- Other examinations performed:
Clinical signs: skin, fur, eyes, occurrence of secretions and excretions, autonomic activity, changes in gait, posture and the presence of convulsions.
Body weight: body weight gain for each week of the study (0-7 days, 7-14 days).
Gross pathology.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived until the scheduled termination of the study.

Clinical signs:

other: All animals were normal during the entire observation period. Exposed skin was not found to be altered by the test substance.

Gross pathology:

All animals were normal at terminal necropsy.

Other findings:

No noteworthy sex difference in the response to the test substance was derived from clinical observations or post-mortem findings.

Synopsis of Results

Sex	Animal	Dose	Number of animals
	Nos.	(mg/kg)	exposed	affected	deceased
Male	1-5	2000	5	1	0
Female	6-10	2000	5	0	0

Interpretation of results:

other: Not classified (CLP Regulation EC no. 1272/2008)

Conclusions:

LD50 value of test article Wasox-MMAC2 in rats by dermal route at 24 h exposure period is higher than 2000 mg/kg bw.

Executive summary:

The Acute Dermal Toxicity assay for the test substance Wasox-MMAC2 was performed according to OECD 402 Guideline in Sprague Dawley rats. 5 animals per sex were treated with a single dose of 2000 mg/kg body weight (limit test). The test material was applied via a patch to an area of approximately 6.5 x 8 cm on the dorsal thoracal region, and covered by a semi-occlusive dressing. The duration of the exposure was 24 hours. Clinical signs and body weights were monitored for 14 days after administration and all animals were subjected to gross necropsy. All animals survived until the scheduled termination of the study. The body weights were inconsplcuous in males during the study. No body weight gain was observed in one female in the first week after administration (0 -7 days) but was inconspicuous in all females in the second (7 - 14 days). All animals were normal during the entire observation period and at terminal necropsy. The dermal LD50 of the test substance was > 2000 mg/kg body weight.

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

The study is GLP compliant and has Klimisch score = 1.

Additional information

Acute toxicity, oral: Key study: The Acute Toxic Class Method assay for the test substance was performed in rats according to OECD 423 Guideline and GLP. The oral LD50 of the test article Wasox-MMAC2 in female rats was higher than 2000 mg/kg bw.

Acute toxicity, dermal: The Acute Dermal Toxicity assay for the test substance was performed according to OECD 402 Guideline in rats. LD50 value of test article Wasox-MMAC2 in rats by dermal route at 24 h exposure period is higher than 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint

Only one study available.

Justification for selection of acute toxicity – inhalation endpoint

According to REACH Annex VIII, column 2: In addition to the oral route, for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. If there is only one route of exposure, information for only that route need be provided. The information is provided for dermal route.

Justification for selection of acute toxicity – dermal endpoint

Only one study available.

Justification for classification or non-classification

Based on the available data on oral and dermal acute toxicity (LD50 > 2000 mg/kg bw), the substance is not classified for acute toxicity according to CLP Regulation (EC) no. 1272/2008.