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

Acute Toxicity: oral

Administrative data

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.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

3-aminopropyltriethoxysilane

EC Number:

213-048-4

EC Name:

3-aminopropyltriethoxysilane

Cas Number:

919-30-2

IUPAC Name:

3-(triethoxysilyl)propan-1-amine

Test animals

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

Administration / exposure

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)

Results and discussion

Effect levels

Effect levels 1

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

Effect levels 2

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

Effect levels 3

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)

Effect levels 4

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

Any other information on results incl. tables

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).	-

Applicant's summary and conclusion

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.