(3-chloropropyl)dimethoxymethylsilane

Endpoint summary

Description of key information

In an acute toxic class study, conducted to OECD Test Guideline 423 and in compliance with GLP (LPT, 2002a, Reliability Score 1), the acute oral LD50 of 3-chloropropyl(dimethoxy)methylsilane (CAS 18171 -19 -2; EC No. 242 -056 -0) was in the range 200-2000 mg/kg bw in rats.

 

There are no measured acute dermal toxicity data for 3-chloropropyl(dimethoxy)methylsilane. Therefore, data have been read across from the structurally-related 3-chloropropyl(diethoxy)methylsilane. In an acute dermal limit study (Hüls AG, 1997b), conducted according to OECD Test Guideline 402 and in compliance with GLP, the dermal acute LD50 for the related substance, 3-chloropropyl(diethoxy)methylsilane was greater than 2000 mg/kg bw in Wistar rats.

There are no acute inhalation studies on 3-chloropropyl(dimethoxy)methylsilane or related analogue substances.

An acute dermal toxicity study conducted according to OECD Test Guideline 402 will be conducted and added to the dossier when available.

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:

04.03.2002 to 13.08.2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: CD/Crl:CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH
- Age at study initiation: Males: 41 days; Females: 48 days
- Weight at study initiation: Males: 206-224 g; Females: 172-197 g
- Fasting period before study: 16 hours before treatment
- Housing: Type III Makrolon cages
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: At least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09.04.2002 To: 02.05.2002

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: No data
- Amount of vehicle: No data
- Justification for choice of vehicle: Not stated, but assumed to be low toxicity
- Lot/batch no.: No data
- Purity: No data


MAXIMUM DOSE VOLUME APPLIED: 1.96 ml/kg bw


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Limit dose

Doses:

200 and 2000 mg/kg bw

No. of animals per sex per dose:

Three

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations: before and immediately at 5, 15, 30 and 60 minutes, as well as at 3, 6 and 24 hours after administration. Weight: before and then weekly after administration
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathological examination.

Statistics:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 200 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg bw resulted in one male and two female deaths. No deaths at 200 mg/kg bw

Clinical signs:

other: All animals of both sexes showed slight to moderately reduced motility, slight to moderate ataxia, slight to moderately reduced muscle tone and slight to moderate dyspnoea from 15 minutes up to 24 hours after administration at 2000 mg/kg bw. There were no

Gross pathology:

No abnormalities were found.

Other findings:

No other findings.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In an acute toxic class study, conducted to OECD Test Guideline 423 and to GLP (reliability score 1), the acute oral LD50 for 3-chloropropyl(dimethoxy)methylsilane was in the range 200-2000 mg/kg bw in rats. All animals of both sexes showed slight to moderately reduced motility, slight to moderate ataxia, slight to moderately reduced muscle tone and slight to moderate dyspnoea from 15 minutes up to 24 hours after administration at 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

200 mg/kg bw

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:

07.10.1996 to 24.10.1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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
- Age at study initiation: No data
- Weight at study initiation: 200-300 g (variation did not exceed ±20% of mean body weight)
- Fasting period before study: No data
- Housing: Individually in Makrolon type II 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): 22 ±3
- Humidity (%): 30-70
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 07.10.1996 To: 24.10.1996

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsolumbar
- % coverage: 10 % of body surface clipped
- Type of wrap if used: Semi-occlusive


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


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.03 cm3/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were checked at least daily for mortalities, they were observed for clinical signs soon after dosing and at regular intervals for the remainder of Day 0 (day of dosing), then daily until the end of the 14 day observation period. Body weights were recorded on days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examinations.

Statistics:

None done

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: There were no clinical signs.

Gross pathology:

No findings.

Other findings:

There were no other findings.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal limit study (reliability score 1) conducted to OECD 402 and GLP, the dermal acute LD50 for 3-chloropropyl(diethoxy)methylsilane was greater than 2000 mg/kg bw in Wistar rats. There were no significant clinical effects.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Additional information

In an acute toxic class study, conducted according to OECD Test Guideline 423 and in compliance with GLP (LPT, 2002a), the acute oral LD50 of 3-chloropropyl(dimethoxy)methylsilane was in the range 200-2000 mg/kg bw in rats. All animals of both sexes showed slight to moderately reduced motility, slight to moderate ataxia, slight to moderately reduced muscle tone and slight to moderate dyspnoea from 15 minutes up to 24 hours after administration at 2000 mg/kg bw.  

Acute oral toxicity studies on the analogue substances, 3-chloropropyl(trimethoxy)silane (Hüls, 1993a), 3-chloropropyl(triethoxy)silane (Dow Corning Corporation, 1995) and 3-chloropropyl(diethoxy)methylsilane (Hüls AG, 1997), are included in support of the read-across for other endpoints. An acute oral toxicity test on chloromethyl(triethoxy)silane (Harlan, 2012) is included in support of the read-across justification discussion on bias in selection of analogue group substances.

There are no acute dermal toxicity data for 3-chloropropyl(dimethoxy)methylsilane. Therefore data have been read across from the structurally-related 3-chloropropyl(diethoxy)methylsilane. In an acute dermal limit study (Hüls AG, 1997b), conducted according to OECD Test Guideline 402 and in compliance with GLP, the dermal acute LD50 for the related substance, 3-chloropropyl(diethoxy)methylsilane, was greater than 2000 mg/kg bw in Wistar rats. There were no significant clinical effects.

Acute dermal toxicity studies on the analogue substances, 3-chloropropyl(trimethoxy)silane (Hüls, 1993b) and 3-chloropropyl(triethoxy)silane (Dow Corning Corporation, 1995), are included in support of the read-across for the analogue group.

There are no acute inhalation studies on 3-chloropropyl(dimethoxy)methylsilane or the analogue substances.

See Section 13 of IUCLID for the read-across justification reports.

Justification for classification or non-classification

Based on the available acute toxicity data, 3-chloropropyl(dimethoxy)methylsilane is classified 'Acute Toxic 4 (oral)' with the hazard statements 'H302: Harmful if swallowed according to Regulation (EC) No 1272/2008. No classification is required for the dermal and inhalation routes.