3-aminopropyltriethoxysilane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

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 798.1100 (Acute Dermal 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 GLP 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

Molecular formula:

C9H23NO3Si

IUPAC Name:

silane

Test animals

Species:

rabbit

Strain:

New Zealand White

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: 2-3 kg
- Fasting period before study: no
- Housing: no details given
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
no details given

IN-LIFE DATES: no details given

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: no details
- Type of wrap if used: impervious wrap covered by Vetrap bandage tape

REMOVAL OF TEST SUBSTANCE
excess liquid removed - no further details
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: 1, 2, 4 or 8 ml/kg bw
- Concentration: neat
- Constant volume: no

Duration of exposure:

24 h

Doses:

8, 4, 2, and 1 ml/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: observations daily for 14 days; body weights on days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, microscopic examination of limited range of tissues

Statistics:

Moving average method (Thompson, 1947; Weil, 1983)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4.29 mL/kg bw

95% CL:

> 2.9 - < 6.34

Remarks on result:

other: Equivalent to 4076 mg/kg bw

Mortality:

Among groups of males and groups of females, 5/5 and 2/5 died at 8 and 4 ml/kg bw, respectively. There were no deaths at the lower doses of 1 and 2 ml/kg bw. See table 1.

Clinical signs:

other: General signs of toxicity included sluggishness, prostration and diarrhoea. Blood loss around the rectal and urogenital areas were also widespread. See table 1.

Gross pathology:

Treatment-related changes were detected in the following organs: kidney, lungs, liver, stomach, urinary bladder and urethra (see table 2). The kidney was identified as the target organ.

Other findings:

Microscopic examinations (on 2 rabbits/sex for the upper dose groups, 1/sex for the lower dose groups) identified acute renal necrosis in those that died (at 8 and 4 ml/kg bw) with accompanying tubular proteinosis and necrosis or other changes to gastric mucosa. Only mild kidney changes were reported in those of the 4 ml/kg bw groups that survived. No clear treatment-related effects were identified in the urinary bladder. Skin changes were seen in all treated groups, from acute necrotic changes in those that died to inflammation and vascular changes in survivors.

Any other information on results incl. tables

Table 1: Number of animals dead and with evident toxicity, and time range within which mortality occurred

Dose (ml/kg bw)	Mortality (dead/total)			Time range of deaths (days)	Number with evident toxicity
	Male	Female	Combined		Male	Female
1	0/5	0/5	0/10	-	1/5: substantial bleeding around rectal area on day 1, recovery on day 2	1/5: diarrhoea on day 1, recovery on day 2
2	0/5	0/5	0/10	-	1/5: substantial bleeding around rectal area on day 1, recovery on day 4	2/5: substantial bleeding around rectal area on day 1. 1/5: sluggishness on day 1. Recovery on day 2
4	2/5	2/5	4/10	2-3	Victims: 2/2 sluggish, unsteady gait; 1/2 mucus around rectal area, mucus and blood clots under cage on day 2 Survivors: sluggish on day 1. 2/3 had rectal blood loss on day 1. Recovery on days 2-3.	Victims: 2/2 sluggish, blood loss around rectal and vaginal areas on day 1. 1/2 unsteady gait, diarrhoea on day 2 Survivors: sluggishness and blood loss from rectum on day 1. Blood under cage on day 2. 1/3 was emaciated on day 7. Recovery of 2 survivors on day 3.
8	5/5	5/5	10/10	1-2	Sluggishness, prostration, blood loss from urogenital or rectal areas, or salivation.	Sluggishness, prostration, unsteady gait or perianal discharge.

 

Table 2: Effect on body weight and gross pathology

Dose (ml/kg bw)	Mean body weight (kg) (days 0/7/14)		Gross Pathology
	Male	Female	Male	Female
1	2.5/2.6/2.8	2.5/2.6/2.8	No remarkable findings	No remarkable findings
2	2.7/2.6/2.8	2.4/2.4/2.6	Lungs (2/5) dark red or pink	No remarkable findings
4	2.6/2.2/2.4	2.8/2.3/2.6	Victims: lungs (1/2) dark red; stomach (2/2) discoloured; kidney (1/2) haemorrhaged; bladder (1/2) dark red clots; liver (1/2) mottled tan Survivors: lungs mottled or with dark red foci	Victims: lungs (1/2) bright red; stomach (1/5) areas adhered to walls; kidneys haemorrhaged; Urinary bladder (2/2) filled with red liquid; urethra (1/2) haemorrhaged; Survivors: lungs dark red or mottled
8	2.4/-/-	2.4/-/-	Lungs (2/5) bright red, mottled; livers mottled tan; stomachs with haemorrhage (1/5) or mucus (2/5); kidneys haemorrhaged (1/5) or tan (2/5); urinary bladder (2/5) filled with red liquid.	Lungs mottled red or pink; livers (2/5) mottled tan; stomachs with mucus; kidneys (1/5) tan.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Not classified according to Regulation (EC) No 1272/2008

Conclusions:

A reliable study conducted largely in compliance with a standard guideline and probably in accordance with GLP, identified an LD50 of 4.29 ml/kg bw in male and female rabbits (equivalent to 4076 mg/kg bw), with some evidence of toxicity at the lowest tested dose of 1 ml/kg bw.