Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Oral (OECD 423), rat: LD50 > 2457 mg/kg bw (limit test)
Inhalation: no data (data waiving according to Column 2 of REACH Annex VIII, Section 8.5.2)
Dermal: (OCED 402), rat: LD50 > 2457 mg/kg bw (limit test)

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
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)
Version / remarks:
adopted 1996
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: CRL:(WI) BR (outbred, SPF quality)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Germany
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: Females (153 ± 2 g); Males (206 ± 10 g)
- Fasting period before study: overnight
- Housing: 3 animals per sex per cage
- Diet: standard pelleted laboratory animal diet (from Carfil Quality BVBA, Oud-Turnhout, Belgium), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (Fluctuations were observed, but were not considered to be relevant)
- Humidity (%): 50 (Fluctuations were observed, but were not considered to be relevant)
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs light
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
2.17 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: no data.
Doses:
2457 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality/viability twice daily. Body weights were determined at day 1 (pre-administration), 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs were determined at periodic intervals at day 1 and once daily until day 15.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 457 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Sex:
male/female
Dose descriptor:
LD50 cut-off
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
other: Uncoordinated movements were noted in all females on the day of treatment (day 1). No clinical signs of toxicity were noted in the males.
Gross pathology:
No abnormalities were observed.
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In an acute oral limit test, conducted according OECD 423 and in accordance with GLP (reliability score 1), there was no mortality or marked systemic effect in rats at 2457 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was conducted according to an 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:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted 1987
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:(WI) BR (outbred, SPF quality)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: Males (307 ± 29 g), Females (215 ± 7 g)
- Fasting period before study: no data
- Housing: single housing in polycarbonate cages
- Diet: standard pelleted laboratory animal diet (from Carfil Quality BVBA, Out-Turnhout, Belgium), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (Fluctuations were observed, but were not considered to be relevant)
- Humidity (%): 50 (Fluctuations were observed, but were not considered to be relevant)
- Air changes (per hr): 15
- Photoperiod: 12 hrs dark / 12 hrs light
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 18 cm² for females, 25 cm² for males
- % coverage: 10%
- Type of wrap if used: surgical gauze patch covered with aluminium foil and Coban flexible bandage

REMOVAL OF TEST SUBSTANCE
- Washing: removal of the test substance and cleaning of residues with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount applied: 2.17 mL/kg bw (equivalent to 2457 mg/kg bw, calculated with a density of 1.13 g/cm³)
- Concentration: undiluted
- Constant volume or concentration used: yes
Duration of exposure:
24 h
Doses:
2457 mg/kg bw
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 twice daily for mortality/viability. The body weights were determined at day 1 (pre-administration), day 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs were determined at periodoc intervals at the day of dosing (day 1), and once daily thereafter until day 15.
Statistics:
No statistical analysis was performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 457 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
No mortality occurred.
Clinical signs:
other: Red staining of the snout, head or neck was observed among several animals on days 1 and 2. These findings were not considered to be substance-related as they are typically noted in association with the bandage application procedures. Focal erythema was s
Gross pathology:
No abnormalities were observed.

Table 1: Results of the acute dermal toxicity study.

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Males

2457

0/1/5

4 h - day 2

---

0

Females

2457

0/4/5

4 h - day 10

---

0

LD50 = > 2457 mg/kg bw
     

* first number = number of dead animals 

 second number = number of animals with clinical signs

 third number = number of animals used 
Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In an acute dermal toxicity study conducted in compliance with OECD 402 and in accordance with GLP (reliability score 1), there were no mortality or other adverse effects observed at 2457 mg/kg bw. (24 hour exposure) (LD0 and LD50 > 2457 mg/kg bw).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The study was conducted according to an OECD test guideline and in compliance with GLP.

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. 

Two studies were available for assessment of acute toxicity of ureidopropyltrialkoxysilane, mixed methoxy and ethoxy esters.

In the key oral toxicity study, which was conducted in compliance with GLP and according to the OECD TG 423, a LD50 > 2457 mg/kg bw was reported (NOTOX, 1999b). Three male and female Wistar rats were dosed with a limit dose of 2.17 ml/kg bw (equivalent to 2457 mg/kg bw) by gavage. No mortality occurred within the observation time of 14 days. No further clinical signs or necropsy findings were observed.

In the key dermal toxicity study, which was conducted in compliance with GLP and according to the OECD TG 402, an LD50 > 2457 mg/kg bw was reported (NOTOX, 1999c). Five male and female Wistar rats were treated with a limit dose of 2.17 ml/kg bw (equivalent to 2457 mg/kg bw) for 24 h under occlusive conditions. No mortality occurred and no necropsy findings were observed within the observation time of 14 days. Red staining of the snout, head or neck was observed among several animals on days 1 and 2. These findings were not considered to be substance-related as they are typically noted in association with the bandage application procedures. Focal erythema was seen in the treated skin-area of three females during the observation period. Signs of necrosis and scabs were also seen in one of these animals. The animals had recovered from the symptoms between day 6 and 11.


Justification for classification or non-classification

The available data on acute toxicity of the registered substance 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.