hydrolysis products of 3-(triethoxysilyl)propan-1-amine

Endpoint summary

Description of key information

Read-across from 3-(triethoxysilyl)propan-1-amine (CAS 919-30-2)
Calculated LD50 values for hydrolysis products of 3-(triethoxysilyl)propan-1-amine (15%) is based on mixture rules:
Oral (EPA OTS 798.1175), male rat: LD50 = 17927 mg/kg bw
Oral (EPA OTS 798.1175), female rat: LD50 = 9946 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:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study conducted according to a national standard method, in a manner closely resembling OECD 401 (now deleted); GLP status is unclear.

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

Version / remarks:

(as stated in SIAR, 2003, not evident from study report seen by this reviewer)

GLP compliance:

not specified

Remarks:

SIAR (2003) notes that this laboratory was certified at the date of this study

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 details given
- Age at study initiation: no details given
- Weight at study initiation: 200-300 g
- Fasting period before study: overnight
- Housing: no details given
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: no details given

ENVIRONMENTAL CONDITIONS
no details given

IN-LIFE DATES: no details given

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
n/a

MAXIMUM DOSE VOLUME APPLIED: 4 ml/kg bw

Doses:

1, 2, and 4 mL/kg bw in males; 1, 1.41 and 2 mL/kg bw in females; corresponding to 950, 1900, and 3800 mg/kg bw in males; 950, 1340, and 1900 mg/kg bw in females

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: observations daily, weighing weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (kidney and urinary bladder of: 2 males at 4 ml/kg bw; 2 males and 3 females at 2 ml/kg bw.

Statistics:

Moving Average Method (Thompson, 1974; Weil, 1983)

Sex:

male

Dose descriptor:

LD50

Effect level:

2.83 mL/kg bw

Based on:

test mat.

95% CL:

1.61 - 4.98

Remarks on result:

other: corresponding to 2689 mg/kg bw

Sex:

female

Dose descriptor:

LD50

Effect level:

1.57 mL/kg bw

Based on:

test mat.

95% CL:

1.34 - 1.85

Remarks on result:

other: corresponding to 1492 mg/kg bw

Sex:

male

Dose descriptor:

LD50

Effect level:

17 927 mg/kg bw

Based on:

other: hydrolysis products of 3-(triethoxysilyl)propan-1-amine (15%)

Remarks on result:

other: based on hydrolysis products of 3-(triethoxysilyl)propan-1-amine (15%) (mixture rules)

Sex:

female

Dose descriptor:

LD50

Effect level:

9 946 mg/kg bw

Based on:

other: hydrolysis products of 3-(triethoxysilyl)propan-1-amine (15%)

Remarks on result:

other: based on hydrolysis products of 3-(triethoxysilyl)propan-1-amine (15%) (mixture rules)

Mortality:

Deaths at 1340 and 1900 mg/kg bw in females and at 1900 and 3800 mg/kg bw in males. No deaths in either sex at 950 mg/kg bw. See table 1.

Clinical signs:

See table 1

Body weight:

See table 1

Gross pathology:

See table 2

Other findings:

- Histopathology: examination of the kidneys and urinary bladders of a selected group revealed tubular necrosis in those that died and some evidence of lesser kidney damage in those that survived (see table 2).
- Potential target organs: kidney

Table 1: Number of animals that died, time range for mortality, body weight change and overt toxicity

Dose (mg/kg bw)	Mortality (dead/total)			Time range of deaths (days)	Mean body weights (days 0/7/14) (g)		Overt toxicity
	Male	Female	Combined		Male	Female	Male	Female
950	0/5	0/5	0/10	-	238/278/304	211/231/241	None.	Sluggishness, recovery at 2 days.
1340	-	1/5	-	1	-	212/227/234	-	Sluggishness, periurogenital staining (positive for blood), red encrusted fur around nose; survivors recovered at 2 days.
1900	1/5	5/5	6/10	2-4	234/251/302	223/-/-	Sluggishness, unkempt appearance, periurogenital brown staining, red encrusted fur around nose and eyes, closed eyelids, emaciation and diarrhoea. Survivors recovered at 5 to 9 days.	Sluggishness, lacrimation, unkempt appearance, red encrusted fur around nose and eyes and diarrhoea.
3800	4/5	-	-	1-2	244/254/283	-	Sluggishness, lacrimation, kyphosis (curvature of the thoracic spine), piloerection and red encrusted fur around nose. Survivor recovered at 3 days.	-

 

Table 2: Gross and microscopic examinations

Dose (mg/kg bw)	Gross examination		Microscopic examination of kidneys and urinary bladder
	Male	Female	Male	Female
950	Nothing remarkable.	Nothing remarkable.	-	-
1340	-	Victim: lungs dark red; stomach (glandular) white to dark red; intestine filled with yellow liquid. Survivors: nothing remarkable.	-	-
1900	Victim: bright red lungs; dark red (glandular) stomachs filled with light brown liquid. Survivors: nothing remarkable.	Victims: lungs bright pink; stomachs (glandular) dark red or mottled; stomachs and intestines filled with light brown liquid; intestines of one yellow; kidneys dark red.	Examined 2 survivors: moderate renal tubular hyperplasia (indicative of prior necrosis) and mild tubular mineralization in 1; no urinary bladder lesions	Examined 3 victims: moderate tubular necrosis; mild to moderate tubular mineralization; moderate kidney congestion; no urinary bladder lesions
3800	Victims: dark red, mottled lungs; dark red (glandular) stomachs; stomachs and intestines filled with yellow liquid; spleen mottled, dark red. Survivor: nothing remarkable.	-	Examined 2 victims: moderate tubular necrosis; marked kidney congestion; epithelial necrosis in the urinary bladder (only 1 rat examined).	-

Interpretation of results:

other: hydrolysis products of 3-(triethoxysilyl)propan-1-amine (15%): no classification

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

A reliable study conducted very largely in compliance with a standard guideline and probably in accordance with GLP, identified LD50 values of 1492 and 2689 mg/kg bw in female and male rats, respectively. However, based on the fact that the hydrolysis product is formed in aqueous solutions of 3-(triethoxysilyl)propan-1-amine where the concentration range of 3-(triethoxysilyl)propan-1-amine is > 0.1 - < 16% (w/w), the available acute oral toxicity study represents a worst case assumption. With respect to mixture rules, the LD50 value for hydrolysis products of 3-(triethoxysilyl)propan-1-amine (15%) is 9946 mg/kg bw for females and 17927 mg/kg bw for males. Thus, there is no need for classification.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

9 946 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties. Read-across is justified as 3-(triethoxysilyl)propan-1-amine hydrolyses rapidly in water resulting in the target substance (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are no data available on acute toxicity of “hydrolysis products of 3-(triethoxysilyl)propan-1-amine” (EC No. 939-125-9). In order to fulfil the standard information requirements set out in Annex VII, 8.5., read-across from a structurally related substance is conducted in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

The read-across is based on the hypothesis that the analogue substance, 3-(triethoxysilyl)propan-1-amine, hydrolyses rapidly in water resulting in the target substance. It can be expected that both the target and the source substance have similar behaviour under aqueous conditions. The target substance consists of 3-aminopropylsilanetriol and ethanol which are formed directly after hydrolysis and several condensation products such as dimers, trimers as well as polymers of siloxanes having similar functional groups (-O-Si- or HO-Si-). Therefore, it is considered that the target and the source substance are in one class of compounds and structural differences are not supposed to contribute to significant differences in activity with respect to eco- and human toxicological endpoints. A detailed analogue approach justification is provided in the technical dossier (Please refer to IUCLID Section 13 for further information).

3-(triethoxysilyl)propan-1-amine was administered by gavage at dose levels of 1, 2 and 4 mL/kg bw (corresponding to 950, 1900 and 3800 mg/kg bw) to 5 male rats/group and 1, 1.41 and 2 mL/kg bw (corresponding to 950, 1340 and 1900 mg/kg bw) to 5 female rats/group. The mortality was 0, 1 and 4 for the males and 0, 1 and 5 for the females, respectively, listed by increasing dose. In the rats that died, bright to dark red lungs and dark red grandular stomachs were noted. The intestines (in some case also the stomachs) were filled with light brown to yellow liquids. Examination of the kidneys and urinary bladders revealed tubular necrosis in those that died and some evidence of lesser kidney damage in those that survived. Signs of toxicity included sluggishness, lacrimation, kyphosis, an unkempt appearance, piloerection, staining on the fur, closed eyelids, emaciation and diarrhea. Survivors recovered at 2 to 9 days.

There were no remarkable gross pathologic findings for the survivors. The LD50 was calculated to be 1492 mg/kg bw for females and 2689 mg/kg bw for males.

Based on the fact that the hydrolysis product is formed in aqueous solutions of 3-(triethoxysilyl)propan-1-amine where the concentration range of 3-(triethoxysilyl)propan-1-amine is > 0.1 - < 16% (w/w), the available acute oral toxicity study represents a worst case assumption. With respect to mixture rules, the LD50 value for hydrolysis products of 3-(triethoxysilyl)propan-1-amine (15%) is 9946 mg/kg bw for females and 17927 mg/kg bw for males.

Thus, there is no need for classification.

Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – inhalation endpoint
No study required since exposure of humans via inhalation is unlikely taking into account the physico-chemical properties of the substances and the lack of exposure to aerosols under normal conditions of use.

Justification for selection of acute toxicity – dermal endpoint
Testing by the dermal route does not need to be conducted as the substance does not meet the criteria for classification as acutely toxic by the oral route and no systemic effects have been observed in in-vivo studies with dermal exposure (skin irritation, skin sensitisation). This is in accordance with the "Draft Commission Regulation amending Annexes VII and VIII to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) as regards skin corrosion/irritation, serious eye damage/eye irritation, skin sensitisation and acute toxicity".

Justification for classification or non-classification

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