Registration Dossier

Administrative data

Description of key information

Oral (OECD 401), rat: LD50 >5000 mg/kg bw
Inhalation: no data available
Dermal (OECD 402), rat: LD50 >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:
05 Feb 1996 - 28 June 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Albino rat
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Crl:CD BR
- Source: Charles River Breeding Laboratories, Inc. Portage, MI, USA
- Age at study initiation: young adult
- Weight at study initiation: 231-300 g
- Fasting period before study: 18-20 h prior to dosing
- Housing: Individual in suspended wire-mesh cages
- Diet: Purim@ Certified Rodent Chow@ #5002, ad libitum. Analysis of feed was performed and provided by the manufacturer.
- Water: municipal water, ad libitum. Water was analysed in accordance with Standard Operating Procedures.
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.0-22.3 (71.6-72.1 °F)
- Humidity (%): 43.7-50.0
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 4.39 ml/kg bw

DOSAGE PREPARATION:
A sufficient amount of test material was transferred from the original container to a labeled storage vessel. A stir bar was added, and the test material was maintained on a magnetic stir plate prior to dispensation and throughout the dosing procedure.

RATIONALE FOR DOSE SELECTION:
Prior to initiation of the main study, a range-finding study was conducted in which groups of one male and one female rat were dosed at levels of 500, 1000, 2000, 3500 and 5000 mg/kg bw. There were no deaths during the range-finding study. Based on these results, 5000 mglkg was selected as the first level on the main study.
Doses:
Range-finding test: 500, 1000, 2000, 3500 and 5000 mg/kg bw
Main study: 5000 mg/kg bw
No. of animals per sex per dose:
Range-finding test: 1
Main study: 5
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: The rats were observed at approximately 1.0, 3.0 and 4.0 hours post-dose on Day 0 and twice daily (morning and afternoon) thereafter for 14 days.
- Frequency of weighing: Body weights were obtained and recorded on study days -1, 0 (initiation), 7 and 14 (termination).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, and gross pathology (major organ systems of the cranial, thoracic and abdominal cavities for all animals)
Preliminary study:
There were no deaths during the range-finding study. Based on these results, 5000 mg/kg bw was selected as the first level on the main study.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
There were no deaths during the study.
Clinical signs:
Three rats had wet and/or dried yellow urogenital staining. Yellow urogenital staining is a common, non-specific finding in acute studies that, in isolation, is not evidence of significant toxicity. Clear ocular discharge and mucoid feces were noted for one female animal. There were no other clinical findings. All animals appeared normal by day 3 or earlier and throughout the remainder of the study.
Body weight:
There were no remarkable changes or differences in body weights.
Gross pathology:
At the terminal necropsy, dark red lungs were noted for three rats. This finding was not considered to be test material-related as it is often noted in animals that have been euthanised by carbon dioxide inhalation. There were no other gross necropsy findings.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
The test material was investigated for acute oral toxicity according to the OECD TG 401, and in compliance with GLP. The undiluted test material was administered once via oral gavage to 5 Crl:CD BR rats per sex at a dose of 5000 mg/kg bw. No mortality occurred and clinical signs were only noted in one female (reversible within 3 days) throughout the study period. Based on these findings, classification for acute oral toxicity according to Regulation (EC) No 1272/2008 is not warranted.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

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:
27 Mar - 10 Apr 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Portage, MI, USA
- Age at study initiation: young adults
- Weight at study initiation: 242 - 295 g
- Housing: animals were housed individually in suspended mesh-bottom cages
- Diet: Purima Certified Rodent Chow #5002 diet, ad libitum
- Water: municipal water, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.9 - 22.3
- Humidity (%): 34.4 - 40.5
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: The test material was applied to the dorsal skin of each animal.
- % coverage: 18 - 23
- Type of wrap if used: The test substance was held in contact with the skin with gauze bandaging. The bandage was secured with nonirritating tape. Collars were applied and remained on the rats for the duration of the exposure to prevent the ingestion of the test material and/or wrappings during the 24 h exposure period.

REMOVAL OF TEST SUBSTANCE
- Washing: The application sites were wiped with disposable paper towels moistened with tepid tap water after the exposure period.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 1.75 ml/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed at approximately 1, 3 and 4 hours post-exposure on day 0 and twice daily for mortality (morning and afternoon) and once daily for clinical observations thereafter for 14 days, respectively. Body weights were obtained and recorded on study days 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: The application sites were examined for erythema, edema and other dermal findings beginning approximately 30 - 60 min after bandage removal and daily thereafter for 13 days. The areas of application were clipped free of hair to facilitate dermal observations on study days 7 and 14.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: neither erythema nor edema were observed
Mortality:
No deaths were observed during the study.
Clinical signs:
Clinical findings were limited to dried red material around the nose and/or forelimb(s) for three rats and wet and dried yellow urogenital staining for two female rats. These findings are typically noted in association with the bandage/collar application procedures and are not considered related to test material application. There were no other clinical findings. All animals appeared normal by day 3 or earlier and throughout the remainder of the study.
Body weight:
There were no remarkable changes or differences in body weights during the study period.
Gross pathology:
A dilated renal (right) pelvis was noted for one female rat at the terminal necropsy. This is considered to be a common, spontaneous finding in rats and was not considered to be related to the test material. There were no other gross necropsy findings for any examined tissues.
Other findings:
- Dermal observations: Six rats showed desquamation. Neither erythema nor edema or other dermal findings were recorded. All dermal responses completely subsided by day 13 or earlier.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008
Conclusions:
In conclusion, under the conditions chosen for this acute dermal toxicity study conducted according to OECD 402 at the limit concentration of 2000 mg/kg bw no clinical signs of toxicity or mortalities were observed. Therefore, the test substance does not need to classified according to Regulation (EC) No 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Acute oral toxicity

A key acute oral toxicity study with [3-(trimethoxysilyl)propyl]urea (CAS 23843-64-3) is available and was performed according to OECD 401 and in compliance with GLP (WIL, 1996a). In this limit test five fasted Albino rats of each sex were administered a single dose of 5000 mg/kg bw of the test substance (CAS 23843-64-3) via oral gavage. The animals were observed for 14 days after administration. No mortalities occurred during the observation period. There were no remarkable changes or differences in body weights during the study period. Clear ocular discharge and mucoid feces were noted for one female animal. There were no other clinical findings. All animals appeared normal by day 3 or earlier and throughout the remainder of the study. No special gross pathological changes were found in all animals. Thus, the acute oral LD50 value for males/females was calculated to be greater than 5000 mg/kg bw. Based on the study results and according to CLP classification criteria, the test substance is not to be classified for acute oral toxicity.

 

Acute toxicity: inhalation

According to Regulation (EC) No 1907/2006, Annex VIII, Section 8.5, Column 2, in addition to the oral route (8.5.1), 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. As information mentioned under 8.5.3 is provided, this requirement is fulfilled by using the most appropriate route of exposure. No acute inhalation toxicity study need to be performed according to the criteria outlined in Regulation (EC) No 1907/2006, Annex VIII, 8.5.2, column 2, since the vapour pressure of the substance is low (2.8E-02 Pa at 25 Pa, QSAR) and the possibility of human exposure is not expected under normal conditions of handling.

 

Acute toxicity: dermal

A key study for acute dermal toxicity with [3-(trimethoxysilyl)propyl]urea (CAS 23843-64-3) is available and was performed according to OECD 402 and in compliance with GLP (WIL, 1996b). In this limit test five Crl:CD rats of each sex were exposed to a single dose of 2000 mg/kg bw of the test substance for 24 h via semi-occlusive dressing and observed for 14 days post-application. No mortalities occurred during the entire study period. No signs of systemic toxicity and no erythema or edema were observed up to the end of the observation period. 6/10 animals showed desquamation, which subsided by Day 13 or earlier. There were no remarkable changes or differences in body weights during the study period. No abnormalities were detected at necropsy at the end of the 14-day observation period. The acute dermal LD50 value was calculated to be greater than 2000 mg/kg bw. Based on the study results and according to CLP classification criteria, the test substance is not to be classified for acute dermal toxicity. 

Justification for classification or non-classification

The available data on acute oral and dermal toxicity of the registered substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are thus conclusive but not sufficient for classification.

No data are available for acute inhalation toxicity.