Dicyclopentyldimethoxysilane

Endpoint summary

Description of key information

In an acute oral toxicity study conducted to the now deleted OECD Test Guideline 401 and in compliance with GLP, the LD50 for dicyclopentyl(dimethoxy)silane (CAS 126990-35-0) was greater than 2000 mg/kg bw in rats (Safepharm Laboratories Ltd., 1995a).

In an acute inhalation study conducted using a protocol similar to OECD Test Guideline 403 and in compliance with GLP, the LC50 for dicyclopentyl(dimethoxy)silane was greater than 22 ppm, as no deaths occurred following a 4-hour exposure to this concentration. This concentration appeared to be the highest attainable under the conditions of this study (DCC, 1993).

In an acute dermal toxicity study conducted according to an EU guideline (EU Method B.3 (Acute Toxicity (Dermal)) and in compliance with GLP, the LD50 for dicyclopentyl(dimethoxy)silane was greater than 2000 mg/kg bw in rats (Huntingdon Research Centre Ltd., 1995b).

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)

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, UK
- Age at study initiation: 5-8 weeks
- Weight at study initiation: Males: 156-186 g; Females: 130-142 g.
- Fasting period before study: yes, overnight
- 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: 14.02.1995 to 02.03.1995

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.05 ml/kg

Doses:

2000 mg/kg

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: The animals were observed for deaths or overt signs of toxicity 0.5, 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 only

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths

Mortality:

No deaths occurred.

Clinical signs:

other: None.

Gross pathology:

No abnormal findings.

Other findings:

None.

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 (Safepharm Laboratories Ltd., 1995), the LD50 for dicyclopentyldimethoxysilane was greater than 2000 mg/kg bw in rats. There were no clinical signs of toxicity, effects on body weight or abnormal macroscopic 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:

06.11.1992 to 11.06.1993

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)

Deviations:

yes

Remarks:

Only one dose tested

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 155-195 g
- Fasting period before study: No
- Housing: Stainless steel cages
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 2
- Humidity (%): 50± 20
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 19.11.1992 To: 07.12.1992

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus and chamber volume: 450 litre stainless steel and glass exposure chambers.
- Method of holding animals in test chamber: None
- Source and rate of air: Ambient filtered with hepa and charcoal filters. 12-15 air changes per hour.
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: Recorded every five minutes during the exposure period.

TEST ATMOSPHERE
- Brief description of analytical method used: Chamber concentrations were measured at least once per hour by a Varian 3400 Gas Chromatography.
- Samples taken from breathing zone: No data

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Nominal: 33 ppm
Actual: 22 ppm
The saturated vapour concentration is approximately 52 ppm. The target exposure concentration of 30 ppm appears to have been unattainable under the conditions of this study as evidenced by the test substance deposition within the vapour generating and the gas chromatography sampling system.

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 daily during the post-exposure period for clinical signs, mortality, general appearance and any evidence of respiratory, dermal, behavioural, nasal or ocular changes. Animals were weighed on days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Gross pathological examination was conducted on all animals. The kidneys were examined microscopically.

Statistics:

Statistical analyses were conducted on body weights. Data were analysed by a two-sided Welch Trend Test. All tests were conducted at the P≤ 0.05 level of significance.

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 22 ppm

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No deaths.

Mortality:

No animals died.

Clinical signs:

other: None

Body weight:

No effects on body weights.

Gross pathology:

Pale kidneys were observed in 9/10 animals.

Other findings:

Histopathological examination of pale kidneys did not reveal any correlative microscopic lesions.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In an acute inhalation study conducted using a protocol similar to OECD Test Guideline 403 and in compliance with GLP, the LD50 for dicyclopentyl(dimethoxy)silane was greater than 22 ppm, as no deaths occurred following a 4-hour exposure to this concentration. This concentration appeared to be the highest attainable under the conditions of this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

205.52 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:

16.02.1995 to 02.03.1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

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: Harlan Olac, UK
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 225-290 g
- Fasting period before study: No
- Housing: Individually in metal cages with wire mesh floors
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Seven days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 16.02.1995 To: 02.03.1995

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorso-lumbar region
- % coverage: Approximately 10%
- Type of wrap if used: Gauze held in place with non-irritating dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with warm water and blotted dry with absorbent paper.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.01 ml/kg bw

Duration of exposure:

24 hours

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: Twice daily for mortality. For clinical effects, animals were observed soon after dosing and at frequent intervals on the day of dosing (Day 1). On subsequent days the animals were observed twice daily. Individual body weights were recorded on Day 1 (prior to dosing), 8 and 15. Individual weekly bodyweight changes and group mean body weights were calculated.
- Necropsy of survivors performed: yes/no
- Other examinations performed: Local dermal effects scored, macroscopic examination

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths

Mortality:

No deaths occurred.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

There were no abnormal findings.

Other findings:

Slight erythema (with or without oedema) was noted in one animal following the removal of the dressings and persisting for the following two days. This was accompanied by spot/scab formation in this and one other rat during the study. In addition desquamation (characterised by dryness/sloughing/scaling) was evident in up to four animals during the latter stage of week 1 and resolving in all instances by day 10.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

In an acute dermal toxicity study conducted to an EU guideline (with a protocol comparable to OECD Test Guideline 402) and in compliacne with GLP, the LD50 for dicyclopentyl(dimethoxy)silane was greater than 2000 mg/kg bw in rats. There were no signs of systemic toxicity, and only mild dermal irritation in a few animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

There are several reliable studies available for oral and dermal routes of exposure. All are of equal quality and conducted in 1995. They all support the key finding that dicyclopentyl(dimethoxy)silane (CAS 126990-35-0) is of low acute toxicity. There is one reliable study for the inhalation route.

In the key acute oral toxicity study conducted according to the now deleted OECD Test Guideline 401 and in compliance with GLP, the LD50 for dicyclopentyl(dimethoxy)silane was greater than 2000 mg/kg bw in rats. There were no clinical signs of toxicity, effects on body weight or abnormal macroscopic findings (Safepharm Laboratories Ltd., 1995a).

In a supporting acute oral toxicity study conducted according to the now deleted OECD Test Guideline 401 and in compliance with GLP, there were no deaths as a result of treatment with dicyclopentyl(dimethoxy)silane. No clinical signs of toxicity, no effect on body weight gain were observed during the observation period. No organ abnormalities were observed at necropsy. The LD50 value was therefore greater than 2000 mg/kg bw in rats (RCC Ltd, 1995a).

In another supporting acute oral toxicity study according to the now deleted OECD Test Guideline 401 and in compliance with GLP, the LD50 for dicyclopentyl(dimethoxy)silane was greater than 2000 mg/kg bw in rats as there were no deaths.

Clinical signs of reaction to treatment included piloerection, abnormal body carriage, abnormal gait and pallor of the extremities, seen in all rats. In addition, lethargy, decreased respiratory rate, partially closed eyelids, increased urine production, increased salivation and gasping/noisy respiration were seen in one or more rats. Recovery was complete in all instances by day 3.

A slightly low bodyweight gain was recorded for two males and one female on day 8, with a similar trend noted for one male on day 15. All other animals achieved satisfactory bodyweight gains throughout the study. Macroscopic examination on day 15 revealed congestion of the thymus in one male. No other abnormalities were noted amongst rats killed on day 15.

In the key acute inhalation study conducted using a protocol similar to OECD Test Guideline 403 and in compliance with GLP, the LC50 for dicyclopentyl(dimethoxy)silane was greater than 22 ppm, as no deaths occurred following a 4-hour exposure to this concentration. This concentration appeared to be the highest attainable under the conditions of this study (DCC, 1993). Pale kidneys were observed in 9/10 animals, however, its associated histopathological examination did not reveal any correlative microscopic lesions.

In the key acute dermal toxicity study conducted to an EU guideline (EU Method B.3 (Acute Toxicity (Dermal)) and in compliance with GLP, the LD50 for dicyclopentyl(dimethoxy)silane was greater than 2000 mg/kg bw in rats. There were no signs of systemic toxicity, and only mild dermal irritation in a few animals. Slight erythema (with or without oedema) was noted in one animal following the removal of the dressings and persisting for the following two days. This was accompanied by spot/scab formation in this and one other rat during the study. In addition, desquamation (characterised by dryness/sloughing/scaling) was evident in up to four animals during the latter stage of week 1 and resolving in all instances by day 10 (Huntingdon Research Centre Ltd., 1995b).

The same results were found in two other supporting studies conducted according to the same OECD Test Guideline 402 and in compliance with GLP (RCC Ltd 1995b., and Safepharm Laboratories Ltd., 1995b).

Justification for classification or non-classification

Based on the available acute toxicity data, dicyclopentyl(dimethoxy)silane is not classified for effects following a single exposure according to Regulation (EC) No 1272/2008.