Registration Dossier

Administrative data

Description of key information

Oral (OECD TG 425): LD50: rat: 1049 mg/kg bw (female).
No measured acute dermal toxicity data are available for the registered substance, trimethoxyphenylsilane, however reliable study are available for the structural analogue substance triethoxyphenylsilane (CAS: 780-69-8, MW ratio: source/target = 0.82).
Dermal (similar to OECD TG 402): LD50: rabbit: 3014 mg/kg (dose given in ml/kg, converted using a specific density of 0.99 g/ml)
MW corrected LD50 = 2471 mg/kg bw.
Inhalation: There are no acute inhalation data 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:
19-07-2009 to 03-02-2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
other: RccHan: WIST
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V. 5961 AD Horst, The Netherlands.
- Age at study initiation: 10 weeks
- Weight at study initiation: 175.9 – 204.7 g
- Fasting period before study: Overnight fasting period prior to intubation.
- Housing: Individually in Makrolon type-3 cages with standard softwood bedding (‘Lignocel’ J. Rettenmaier & Söhne GmbH&CoKG, Rosenberg, Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst, Switzerland) during treatment and observation.
- Diet : Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, as libtum (except for the overnight fasting period prior to intubation and approximately 3-4 hours post dose).
- Water :Community tap water from Füllinsdorf, ad libitum.


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: 19-08-2009 To:14-10-2009
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle:To prevent hydrolysis of the test substance in contact with moisture/water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Limit dose
Doses:
2000 and 550 mg/kg bw
No. of animals per sex per dose:
4 females - 2000 mg/kg bw and 3 females - 550 mg/kg bw.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The animals were examined daily during the acclimatisation period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs once during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2 to 15. Mortality/ viability was recorded once during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2 to 15. Body weights were recorded on day -1 (prior to removal of food), day 1 (prior to administration) and on day 8 and 15. All animals were examined macroscopically after death whether they died spontaneously or were killed in extremis, as well as at the end of the study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology.
Statistics:
The statistical programme (AOT 425 STAT Pgm) version: 1.0,2001 was used.
Sex:
female
Dose descriptor:
LD50
Effect level:
1 049 mg/kg bw
Based on:
test mat.
95% CL:
>= 550 - <= 2 000
Remarks on result:
other: based on an assumed sigma of 0.5.
Mortality:
500 mg/kg bw - No mortality occurred during the study period.
2000 mg/kg bw – All 4 animals died spontaneously or had to be killed in extremis due to the relevant clinical signs observed including an excessive body weight loss in the three sacrificed animals. The severe body weight loss (over 20 %) required the sacrifice of the animals.

Clinical signs:
500 mg/kg bw – No clinical signs were observed in the three treated females (No. 2, 4 and 6) within the first 30 minutes on test day 1. One (No.6) of these animals showed no clinical signs during the entire study. The two other animals were observed with slightly ruffled fur and slight sedation at the 1- and 5- hour readings. The slightly ruffled fur persisted in one (No.4) of these animals on test days 2 and 3. These two animals showed no additional clinical signs during the remainder of the study.

2000 mg/kg bw – Clinical signs were within the first 30 minutes and generally persisted until death occurred. Slight to moderate reffled fur, hunched posture, slight to moderate sedation, tachypnea, bradypnea, labored to deep respiration, slight to moderate poor coordination, cyanosis, red serious rhinorrhea, general bad state of health (weakness) and body weight loss.
Body weight:
500 mg/kg bw – The body weights were within the range commonly recorded for this strain and age.
2000 mg/kg bw – The animals showed a loss of body weight ( -21 % for animal No.7 and -24.6 % for animal No.3 and 5) between the day of treatment (= day 1; fasting period was on day, between test day -1 and test day 1) and the day of sacrifice (test day 4, 5 or 6). No body weight was recorded following the spontaneous death of the first animal treated at 2000 mg/kg on test day 1 and found dead on test day 2.
Gross pathology:
500 mg/kg bw – Necropsy and macroscopic examination revealed no substance-related findings.
2000 mg/kg bw – Light red congested lungs and black brown stomach distended with gas in animal No.1 dosed at 2000 mg/kg bw (which died spontaneously), tan discoloration of kidneys in animal No.3 (killed in extremis) and spleen reduced in size as well as distended stomach in animal No.7 (killed in extremis). Animal No.5 (killed in extremis) showed no macroscopic findings at the unscheduled necropsy .
Interpretation of results:
other: CLP/EU GHS criteria are met, Category 4 classification required according to Regulations (EC) No 1272/2008.
Conclusions:
In an acute oral toxicity study conducted according to OECD 425 and to GLP, the median lethal dose of trimethoxyphenylsilane after single oral administration to female rats observed over a period of 14 days, is: LD50 (female rats)= 1049 mg/kg bw (based on an assumed sigma of 0.5).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 049 mg/kg bw
Quality of whole database:
The study was conducted according to the appropriate OECD test guideline, and in compliance with GLP.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Reason / purpose:
read-across source
Sex:
male
Dose descriptor:
LD50
Effect level:
3 014 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 920 - <= 5 128
Remarks on result:
other: dose given in ml/kg, converted using a specific density of 0.99 g/ml
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008.
Executive summary:

One study is available from the structural analogue triethoxy(phenyl)silane CAS 780 -69 -8. The LD50 for triethoxy(phenyl)silane was estimated to be greater than 2000 mg/kg bw from this study. Thus the same is concluded for trimethoxyphenylsilane. As explained in the justification for type of information, the differences in molecular structure between the target and the source are unlikely to lead to differences in the dermal LD50 that are higher than the typical experimental error of the test method.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
3 654 mg/kg bw
Quality of whole database:
The study was well documented and meets generally accepted scientific principles, but was not conducted in compliance with GLP for the structural analogue substance triethoxy(phenyl)silane (CAS: 780-69-8).

Additional information

Studies were chosen as key when the available study was of relevance and of sufficient quality for classification, labelling and for risk assessment.

 

The key acute oral toxicity study which was conducted in compliance with GLP and according to OECD TG 425, reports an LD50 value of 1049 mg/kg bw (based on an assumed sigma of 0.5 as reported in the study) for female rats after single oral administration with the registered substance. All 4 animals dosed with 2000 mg/kg bw died spontaneously or had to be killed in extremis due to the clinical signs observed, including an excessive body weight loss in the three sacrificed animals, while no mortality occurred in animals dosed with 500 mg/kg bw. At 2000 mg/kg bw the following observations were seen: ruffled fur, slight sedation, light red congested lungs, black brown stomach distended with gas, tan discoloration of kidneys and spleen reduced in size (Harlan Laboratories Ltd, 2010).

No measured acute dermal toxicity data are available for the registered substance, trimethoxyphenylsilane, however data are available for the structural analogue substance triethoxyphenylsilane (CAS: 780-69-8). Since both substances hydrolyse in contact with water to generate the common silanol hydrolysis product, phenylsilanetriol, it is considered that read-across between the substances is appropriate. The molecular weight difference between target and source is 198.29//240.37 = 0.82.

 

The key acute dermal toxicity study was conducted using a protocol that was similar to OECD TG 402, but not to GLP. The LD50value of 3014 mg/kg bw (dose given in ml/kg, converted using a specific density of 0.99 g/ml) was identified for the structural analogue substance triethoxyphenylsilane (Mellon Institute, 1972). The LD50 for the target chemical is MW corrected to be 2471 mg/kg bw.

 

There are no acute inhalation data available.

Justification for classification or non-classification

Based on the available acute oral toxicity study, trimethoxyphenylsilane is proposed to be classified as R22 ‘’Harmful if swallowed’’ according to the criteria of EU Directive 67/548/EEC, and Acute Toxic 4 (oral) under Regulation (EC) 1272/2008. The available data on acute dermal toxicity of the structural analogue substance, triethoxyphenylsilane (CAS: 780-69-8), do not meet the criteria for classification according to Regulation 1272/2008 or EU Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification of the registered substance.