Cyclohexyldimethoxymethylsilane

Endpoint summary

Description of key information

In an acute oral toxicity study conducted according to the now deleted OECD Test Guideline 401 and in compliance with GLP (Safepharm Laboratories Ltd., 1995a), the LD50 for cyclohexyldimethoxymethylsilane was greater than 2000 mg/kg bw in rats.

In an acute aerosol inhalation study conducted using a protocol comparable to OECD Test Guideline 403 and in compliance with GLP (Huntingdon Research Centre Ltd., 1990), the LC50 for cyclohexyldimethoxymethylsilane was greater than 5.53 mg/l in rats (whole-body).

In an acute dermal toxicity study conducted according to OECD Test Guideline 402 and in compliance with GLP (Safepharm Laboratories Ltd., 1995b), the LD50 for cyclohexyldimethoxymethylsilane was greater than 2000 mg/kg bw in rats. There were no signs of systemic toxicity or dermal irritation.

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:

06.07.1995 to 26.07.1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

other: 92/69/EEC

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd
- Age at study initiation: 5-8 weeks
- Weight at study initiation: Males: 155-187 g; Females: 126-146 g
- Fasting period before study: yes
- Housing: Groups of five in polypropylene cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 47-66
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 06.07.1995 To: 26.07.1995

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.14 ml/kg

Doses:

2000 mg/kg bw/day

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for deaths or overt signs of toxicity half, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: Macroscopic examination

Statistics:

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test substance was made.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths occurred.

Mortality:

There were no deaths.

Clinical signs:

other: Common signs of systemic toxicity were hunched posture, lethargy, ataxia and reduced breathing rate with additional signs of laboured breathing, loss of righting reflex and ptosis. One male was comatose four hours after dosing. Animals returned to normal

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

- Organ weights: Not measured
- Histopathology: Not conducted
- Potential target organs: None identified

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In an acute oral toxicity study conducted according to the now deleted OECD Test Guideline 401 and in compliance with GLP (reliability score 1), the LD50 for cyclohexyldimethoxymethylsilane was greater than 2000 mg/kg bw in rats. Common signs of systemic toxicity were hunched posture, lethargy, ataxia and reduced breathing rate with additional signs of laboured breathing, loss of righting reflex and ptosis. One male was comatose four hours after dosing. Animals returned to normal within one day of dosing. There were no other adverse findings.

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

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04.10.1989 to 27.10.1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd
- Age at study initiation: 6-8 weeks (on arrival at lab)
- Weight at study initiation: Approximately 200 g
- Fasting period before study: No
- Housing: Polypropylene cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 35-65
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: 04.10.1989 To: 27.10.1989

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The whole body exposure chambers were of square section and were fitted with pyramidal tops. The chambers were made of perspex.
- Exposure chamber volume: 120 litres
- Method of holding animals in test chamber: Each chamber was divided by wire mesh partitions to provide 10 separate animal compartments.
- Source and rate of air: Described as 'clean, dried air', which was connected to the aerosol generator and the supply pressure was adjusted to give a flow rate of 25 litres/minute measured at the generator outlet tube.
- Method of conditioning air: The compressed air supply to the generator was dried, filtered and oil-free.
- System of generating aerosols: The generator was designed to produce and maintain an atmosphere containing a high proportion of respirable droplets. A flow rate of 0.5 ml/minute test substance to the atomiser was expected to give a concentration of aerosol just in excess of 5 mg/l of air.
- Method of particle size determination: Two samples were taken using a May multistage liquid impinger with acetone/methanol as the trapping agent in each stage (stage 1 - particles >5.5 micrometres; stage 2 - 5.5 to 2.0 micrometres; stage 3 - <2.0 micrometres). The contents of the stages were analysed to determine the particle size distribution in the atmosphere.
- Treatment of exhaust air: Each chamber was positioned inside a large glass walled cabinet equipped with an extractor fan exhausting to atmosphere through a collection filter.
- Temperature, humidity, pressure in air chamber: Approximately 23oC. No data for humidity or chamber pressure.

TEST ATMOSPHERE
- Brief description of analytical method used: Five air samples were taken from the chamber during each exposure and analysed to determine the concentration of test substance. The samples were drawn through an absorption trap, containing approximately 20ml of acetone, at a sampling rate of 2 litres/minute.
- Samples taken from breathing zone: no data

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 81% in respirable range (<5.5 micrometres)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.53 mg/l

No. of animals per sex per dose:

Five

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed continuously during the exposure period for signs of toxicity, and twice daily during the observation period of 14 days. All rats were weighed daily.
- Necropsy of survivors performed: yes
- Other examinations performed: Food and water consumption was measured by cage. At the end of the observation period a detailed macroscopic examination was conducted. Lungs weights were measured. Lungs, liver and kidneys were examined microscopically.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.53 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No deaths

Mortality:

No mortality occurred.

Clinical signs:

other: Partial closing of the eyes, hunched/prone posture, wet snout and slow breathing rate were observed, but are considered consistent with exposure to a mildly irritant aerosol. Wet fur, slow breathing rate, staggering and sensitivity to touch were observed,

Body weight:

There was an initial loss of weight or reduced bodyweight gain 1 -2 days after exposure. Subsequently, there was no difference between controls and treated animals.

Gross pathology:

Lung weights were normal. There were no abnormal macro- or micro-scopic findings.

Other findings:

Food consumption was reduced for 1 -2 days following exposure.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In an acute aerosol inhalation study conducted using a protocol comparable to OECD Test Guideline 403 and in compliance with GLP (reliability score 1), the LC50 for cyclohexyldimethoxymethylsilane was greater than 5.53 mg/l in rats (whole-body). Wet fur, slow breathing rate, staggering and sensitivity to touch were observed, but only on the first day. All animals were normal by Day 1 of the observation period. There was an initial loss of weight or reduced bodyweight gain 1 -2 days after exposure. Subsequently, there was no difference between controls and treated animals. Food consumption was reduced for 1 -2 days following exposure. Lung weights were normal. There were no abnormal macro- or microscopic findings.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5.53 mg/m³ air

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:

12.07.1995 to 26.07.1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: 92/69/EEC, Method B3

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:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd
- Age at study initiation: 10-14 weeks
- Weight at study initiation: Males: 210-238 g; Females: 201-234 g
- Fasting period before study: No
- Housing: Individual during exposure period, and groups of 5/6 at other times, in suspended polypropylene cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 49-60
- Air changes (per hr): Approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12.07.1995 To: 26.07.1995

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back and flanks
- % coverage: Approximately 10%
- Type of wrap if used: Semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with moist cotton wool
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.14 ml/kg

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were checked for mortality and signs of toxicity at 0.5, 1, 2 and 4 hours after dosing and subsequently once daily thereafter. Individual bodyweights were recorded prior to application of the test substance on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: dermal for signs of irritation, macroscopic examination

Statistics:

Mortality data were used to calculate the acute dermal median lethal dose.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were observed.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

No signs of irritation were observed.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In an acute dermal toxicity study conducted to OECD Test Guideline 402 and in compliacne with GLP (reliability score 1), the LD50 for cyclohexyldimethoxymethylsilane was at least 2000 mg/kg bw in rats. There were no signs of systemic toxicity or dermal irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

There are several acute studies available for each route of exposure. For each route the most recent reliable study has been selected as the key study. The other available reliable studies provide supporting evidence for the low acute toxicity of cyclohexyl(dimethoxy)methylsilane.

In the key acute oral toxicity study conducted according to the now deleted OECD Test Guideline 401 and in compliance with GLP (Safepharm Laboratories Ltd., 1995a), the LD50 for cyclohexyl(dimethoxy)methylsilane was greater than 2000 mg/kg bw in rats.

Common signs of systemic toxicity were hunched posture, lethargy, ataxia and reduced breathing rate with additional signs of laboured breathing, loss of righting reflex and ptosis. One male was comatose four hours after dosing. Animals returned to normal within one day of dosing. There were no other adverse findings.

In a supporting acute oral toxicity study conducted using a protocol comparable to the now deleted OECD Test Guideline 401 and in compliance with GLP (reliability score 1),  the male and female combined LD50 for cyclohexyl(dimethoxy)methylsilane was 4071 mg/kg bw in rats (Life Science Research., 1987a). Loss of consciousness was observed at all dose levels, and the animals had in all cases recovered by the second day after treatment. Other clinical signs were irritability, hypo- and hyperactivity, ataxia, hunched posture, flaccid musculature, pallor, cyanosis, pigmented staining of the snout, pigmented orbital secretion, salivation, urogenital soiling, incontinence, ungroomed appearance, piloerection, dorsal hairloss and lacrimation.

In another supporting acute oral toxicity study conducted using a protocol comparable to the now deleted OECD Test Guideline 401, but not in compliance with GLP (reliability score 2), the LD50 for cyclohexyl(dimethoxy)methylsilane was 3000 mg/kg bw (male and female combined) in rats (Huntingdon Research Centre Ltd., 1988a).

In the key acute aerosol inhalation study conducted using a protocol comparable to OECD Test Guideline 403 and in compliance with GLP (Huntingdon Research Centre Ltd., 1990), the LC50 for cyclohexyl(dimethoxy)methylsilane was greater than 5.53 mg/l in rats (whole-body). Wet fur, slow breathing rate, staggering and sensitivity to touch were observed, but only on the first day. All animals were normal by Day 1 of the observation period. There was an initial loss of weight or reduced bodyweight gain 1 -2 days after exposure. Subsequently, there was no difference between controls and treated animals. Food consumption was reduced for 1 -2 days following exposure. Lung weights were normal. There were no abnormal macro- or microscopic findings.

In a supporting acute vapour inhalation study conducted using a protocol comparable to OECD Test Guideline 403 with acceptable restrictions (reliability score 2 based on test concentration being too low - 20 mg/l in guideline compared with 2.06 mg/l tested) and in compliance with GLP,  the LC50 for cyclohexyl(dimethoxy)methylsilane in rats was greater than 2.06 mg/l (Dow Corning Corporation., 1990)

In another acute aerosol inhalation study conducted according to OECD Test Guideline 403 (except no test substance purity information) and in compliance with GLP (reliability score 1), the LC50 for cyclohexyl(dimethoxy)methylsilane was greater than 5.03 mg/l in rats (nose only). Clinical signs immediately after exposure were ataxia, wet fur, exaggerated respiratory movements (persisted until Day 2), reduced respiratory rate and torpidity. After Day 2 all rats were normal in appearance and behaviour. There was no effect on bodyweight. Liver weights were higher than expected, particularly in males. There were no changes noted at necropsy (Life Science Research Ltd., 1988).

In an acute dermal toxicity study conducted to OECD Test Guideline 402 and in compliance with GLP (reliability score 1),  the LD50 for cyclohexyl(dimethoxy)methylsilane was at least 2000 mg/kg bw in rats. There were no signs of systemic toxicity or dermal irritation. The same results were found in two other supporting studies conducted according to the same OECD Test Guideline 402 and in compliance with GLP (Life Science Research., 1987b and Huntingdon Research Centre Ltd., 1989a).

Justification for classification or non-classification

Based on the available acute toxicity data, cyclohexyl(dimethoxy)methylsilane is not classified for acute toxicity or specific target organ toxicity following single exposures according to Regulation (EC) 1272/2008.