Polysulfides, bis[3-(triethoxysilyl)propyl]

Endpoint summary

Description of key information

The key acute oral toxicity study with bis[3-(triethoxysilyl)propyl]polysulfides (CAS No. 211519-85-6, EC No. 915-673-4) was conducted according to a protocol similar to the now deleted OECD Test Guideline 401, but pre-dated GLP (Laboratorium fűr Pharmakologie und Toxikologie, 1977). In this study, the LD50 was concluded to be greater than the highest dose of 15.9 ml/kg bw in male and female rats (equivalent to 17193 mg/kg bw based on a relative density of 1.0813 at 20°C).

 

In the key inhalation acute toxicity study with bis[3-(triethoxysilyl)propyl]polysulfides conducted according to OECD Test Guideline 403 but which pre-dated GLP, an LC50 greater than 7967 mg/m3 in rats exposed for 4 hours was identified. No deaths were reported and clinical signs were minor and transient (RCC Ltd, 1983).

 

In the key dermal acute toxicity study with bis[3-(triethoxysilyl)polysulfides largely conformed to OECD Test Guideline 402 but pre-dated GLP, no mortality or systemic effects were observed in rats treated at 4983 mg/kg bw (Degussa Institute of Toxicology, 1983).

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:

during April and May 1977 (no further details)

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

No guideline is indicated. The method described is similar to the (now deleted) OECD 401.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Sprague Dawley outbred strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: S. Ivanovas GmbH & Co, med. Versuchstierzuchten KG, Postfach 7, D-7964 Kißlegg/Allgäu, GERMANY
- Age at study initiation: 38 days (males), 42 days (females)
- Weight at study initiation: 100-105 g
- Fasting period before study: 15-16 h
- Housing: 1/Macrolon cage type II
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: not stated

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 +/- 0.5
- Humidity (%): 60 +/- 3
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): not stated


IN-LIFE DATES: not stated - experimental work conducted during April and May 1977

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
none

MAXIMUM DOSE VOLUME APPLIED: 15.9 ml/kg bw

Doses:

10, 12.6, 15.9 ml/kg bw

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 28 days
- Frequency of observations and weighing: frequency of clinical observations and body weight measurements not stated
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

None

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 15.9 mL/kg bw

Based on:

test mat.

Remarks on result:

other: equivalent to 17193 mg/kg bw based on relative density of 1.0813 at at 20C

Mortality:

No deaths in any group (see table 1).

Clinical signs:

other: No overt toxicity other than minor reduction in weight gain (see table 1).

Gross pathology:

No significant findings.

Other findings:

None.

Table 1: Number of animals dead or with evident toxicity

Dose (ml/kg bw)	Mortality (dead/total)			Reduced food intake (mean %)	Reduced body weight development (mean %)
	Male	Female	Combined	Days 1,2,7	Days 1,2,7
10	0/10	0/10	0/20	6,4,0	2,4,4,
12.6	0/10	0/10	0/20	10,2,0	4,4,6
15.9	0/10	0/10	0/20	11,4,6	2,0,4

 

Interpretation of results:

GHS criteria not met

Conclusions:

In a reliable acute oral toxicity study conducted according to a protocol similar to the now deleted OECD Test Guideline 401 but pre-dating GLP, an LD50 was concluded to be in excess of 15.9 ml/kg bw in male and female rats (equivalent to 17193 mg/kg bw based on relative density of 1.0813 at 20°C).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 17 193 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 13 to 27 Jan 1983

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: outbred Wistar stock, (kfm:Wistar)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, 4414 Fuellinsdorf, SWITZERLAND
- Age at study initiation: 9 weeks (males), 12 weeks (females)
- Weight at study initiation: 229-268 g (males), 217-272 g (females)
- Fasting period before study: apparently none - food withheld during treatment
- Housing: 5/Macrolon type 4 cage
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 h/ 12 h

IN-LIFE DATES: From: 1983-01-13 To: 1983-01-27

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: PVC nose-only tube-shaped chambers arranged radially around central chamber.
- Exposure chamber volume: 100 l
- Method of holding animals in test chamber: not stated
- Source and rate of air: dynamic, 10 l/min (operated as described in Sachsse et al 1973 & 1976).
- Method of conditioning air: -
- System of generating particulates/aerosols: test material supplied to spray nozzle by Perfusor R ED 1-300 automatic infusion pump. Air flow 600 l/hr; air pressure 3 atmospheres.
- Method of particle size determination: gravimetric (4-stage cascade impactor on Selectron filter)
- Treatment of exhaust air: -
- Temperature, humidity, pressure in air chamber: 22.5° C (SD 0.4); 57% RH (SD 9)
- Oxygen level: 20 % vol

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric (Selectron filter pore size 0.2 microns)
- Samples taken from breathing zone: not stated

VEHICLE
none

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 46% 1-7 microns (2 measurements)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric

Duration of exposure:

4 h

Concentrations:

7967 mg/m3 (measured) (standard deviation 510)

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: mortality and clinical observations 5 times during day 1, then daily; body weights recorded on days 1, 8, 15.
- Necropsy of survivors performed: yes.
- Other examinations performed: clinical signs, body weight.

Statistics:

None.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 7 967 mg/m³ air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: standard deviation 510 mg/m3

Mortality:

No deaths. See table 1.

Clinical signs:

other: Minor clinical signs reported during day 1. See table 1.

Body weight:

No effect on body weight.

Gross pathology:

No treatment-related effects reported.

Other findings:

None

Table 1: Concentrations, exposure conditions and mortality or evident toxicity

Nominal Conc. (ml/h)	Analytical Conc. (mg/m3)	Mean particle size distribution µm	Mortality (males and females/total)	Number with evident toxicity (males and females/total)
60	7967 (SD 510)	46% 1-7	0/10	Day 1: slight dyspnoea, slight exophthalmos or slightly ruffled fur in all exposed animals. Days 2-15: no overt toxicity
0	0	-	no data	-

 SD: standard deviation

Interpretation of results:

GHS criteria not met

Conclusions:

In a reliable study conducted according to OECD Test Guideline 403 but without indication of compliancy to GLP, an LC50 in excess of 7967 mg/m3 in rats exposed for 4 h was identified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 7 967 mg/m³ air

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:

from 23 June to 7 July 1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

See below

Principles of method if other than guideline:

No guideline stated. Study conforms largely to OECD 402 with minor deviations as stated below.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH, Borchen, GERMANY
- Age at study initiation: 10-14 weeks (males); 10-11 weeks (females)
- Weight at study initiation: 224-304 g (males); 161-180 g (females)
- Fasting period before study: 16 h
- Housing: 1/ Macrolon type II cage
- Diet: standard ad libitum
- Water: drinking water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 h/12 h


IN-LIFE DATES: From: 1982-06-23 To: 1982-07-07

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: no details given
- % coverage: -
- Type of wrap if used: no details given

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no details given
- Time after start of exposure: -

TEST MATERIAL
- Amount(s) applied: 4.64 ml/kg bw (4983 mg/kg bw)
- Concentration (if solution): neat

VEHICLE
- none

Duration of exposure:

No details of removal of test material. Observation for 28 days following application.

Doses:

4983 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: 28 days
- Frequency of observations and weighing: no details given on frequency of clinical observations. Apparently body weights were not recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: no details

Statistics:

None.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 983 mg/kg bw

Based on:

test mat.

Mortality:

No deaths recorded during 28 days observation.

Clinical signs:

other: No evidence of treatment-related toxicity, however no details were given of the extent of observations.

Gross pathology:

No treatment-related abnormalities reported.

Other findings:

Eschar, recorded in 8/10 animals, finally resolved on day 13. No further details are given.

No tabulated details of findings are given in this report.

Interpretation of results:

GHS criteria not met

Conclusions:

In a reliable study conducted largely in a manner similar to the OECD Test Guideline 402 but without details about compliancy to GLP, no mortality or systemic effects was found in rats treated at 4983 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

> 4 983 mg/kg bw

Additional information

The key study for acute oral toxicity with bis[3-(triethoxysilyl)propyl]polysulfides was conducted according to a protocol similar to the now deleted OECD Test Guideline 401 but pre-dated GLP. Groups of female and male rats were administered one of the three doses (10, 12.6 and 15.9 ml/kg) of the neat test material by gavage. There were no deaths and no overt toxicity. A minor reduction in body weight gain was recorded which was presumed to be due to slightly reduced food intake. Gross pathology revealed no significant findings. An LD50 of greater than 15.9 ml/kg bw (equivalent to 17193 mg/kg bw based on relative density of 1.0813 at 20°C) was reported (Laboratorium fűr Pharmakologie und Toxikologie, 1977).

 

Two supporting studies with bis[3-(triethoxysilyl)propyl]polysulfides were also available for acute oral toxicity. In a study conducted according to a protocol similar to the now deleted OECD Test Guideline 401 but which was limited in some respects and pre-dated GLP, an LD50 value greater than 30 ml/kg bw (equivalent to 32439 mg/kg bw based on relative density of 1.0813 at 20°C) was determined for male and female rats (TNO, 1979). In the other supporting study, for which very limited details were available and which pre-dated GLP, an LD50 greater than 5000 mg/kg bw was identified (Chemiewerk, 1972).

 

The key study for acute inhalation toxicity with bis[3-(triethoxysilyl)propyl]polysulfides was conducted according to OECD Test Guideline 403 but pre-dated GLP (RCC Ltd, 1983). An LC50 greater than 7967 mg/m³was determined in a 4-hour exposure to an aerosol of the test substance. There were no mortalities or necroscopy findings. Minor clinical signs were reported during Day 1, but these were likely due to discomfort during the exposure procedure than indications of systemic toxicity. During the test study period, there were no signs of overt toxicity. There were no effects on body weight, and gross pathology revealed no treatment related effects.

 

The key study for acute dermal toxicity with bis[3-(triethoxysilyl)propyl]polysulfides was conducted largely in a manner similar to the OECD Test Guideline 402 but pre-dated GLP. In this study, no mortality or systemic effects were observed in rats treated at 4983 mg/kg bw. Eschar was recorded in 8/10 animals, which resolved by Day 13. No treatment-related abnormalities were reported at necropsy (Degussa Institute of toxicology, 1983). The LD50 was >4983 mg/kg bw.

Justification for classification or non-classification

Based on the available oral, dermal and inhalation data, bis[3-(triethoxysilyl)propyl]polysulfides does not require classification for acute toxicity according to Regulation (EC) No. 1272/2008.