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Administrative data

Description of key information

The key study for acute oral toxicity found the test substance harmful, when administered via oral gavage to rats, with acute oral LD50s of 986 (male), 1650 (female) and 1423 mg/kg bw (males and females) calculated. The study was performed in accordance with OECD Test Guideline 401 but not in compliance with GLP

(ASTA Pharma 1987)

. The key study for acute dermal toxicity reports an LD50 value of >4000 mg/kg bw, which was determined in a reliable study conducted according to OECD 402 and in compliance with GLP (Harlan 2011). In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the inhalation route (required in Section 8.5.2) does not need to be conducted as reliable data via the oral and dermal routes are available.

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:
25 November 1986 to 14 August 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: EEC Guideline (84/449/EEC)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co. KG., D-4799 Borchen
- Age at study initiation: 49 to 56 days (males), 63 to 72 days (females)
- Weight at study initiation: 130 to 196 g (males), 132 to 161 g (females)
- Fasting period before study: 16 h
- Housing: singly in Macrolon cages type II
- Diet (e.g. ad libitum): standard diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 November 1986 To: 18 December 1986
Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 215, 316, 464 or 681 mg/ml
- Amount of vehicle (if gavage): 2.15 or 3.16 ml/kg bw (3.16 ml/kg bw given to top dose females only)
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 3.16 ml/kg
Doses:
464, 681, 1000, 1470 mg/kg bw (males and females), 2150 mg/kg bw (females only)
No. of animals per sex per dose:
generally 5 (10 females given 1000 mg/kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: rats were observed "for the first four to 8 hours" (apparently at 0.5, 1, 2, 4 and 8 h) for mortality or clinical signs of toxicity. Animals were then checked for mortality twice daily (only once on weekends and national holidays). For clinical signs of toxicity, animals were observed once daily. Body weights were recorded at the start of the study, and on days 7 and 14 after administration, or after death (provided that the animals survived one day)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
The LD50 values and the slopes of the dose response curves were determined for each sex and for both sexes together by probit analysis with a 95% confidence interval.
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 986 mg/kg bw
Based on:
test mat.
Remarks:
mortality
95% CL:
>= 658 - <= 2 180
Remarks on result:
other: mortality: 0/5 given 464 mg/kg bw, 2/5 given 681 mg/kg bw, 2/5 given 1000 mg/kg bw, 4/5 given 1470 mg/kg bw
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 1 650 mg/kg bw
Based on:
test mat.
Remarks:
mortality
95% CL:
>= 1 252 - <= 4 021
Remarks on result:
other: mortality: 1/5 given 464 mg/kg bw, 0/5 given 681 mg/kg bw, 2/10 given 1000 mg/kg bw, 1/5 given 1470 mg/kg bw, 4/5 given 2150 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 423 mg/kg bw
Based on:
test mat.
Remarks:
mortality
95% CL:
>= 2 049 - <= 3 478
Remarks on result:
other: mortality: 1/10 given 464 mg/kg bw, 2/10 given 681 mg/kg bw, 4/15 given 1000 mg/kg bw, 5/10 given 1470 mg/kg bw, 4/5 given 2150 mg/kg bw
Mortality:
0/5 males given 464 mg/kg bw died.
2/5 males given 681 mg/kg bw died (1 and 24 h after administration)
2/5 males given 1000 mg/kg bw died (1 and 2 h after administration)
4/5 males given 1470 mg/kg bw died (1, 1, 2 and 4 h after administration)

1/5 females given 464 mg/kg bw died (1 h after administration)
0/5 females given 681 mg/kg bw died
2/10 females given 1000 mg/kg bw died (both 2 h after administration)
1/5 females given 1470 mg/kg bw died (1 h after administration)
4/5 females given 2150 mg/kg bw died (one at 0.5 h, the rest 1 h after administration)
Clinical signs:
Signs of toxicity included: hypokinesia, clonic convulsions, decrease of muscle tone, salivation and strenuous breathing.
Stilted gait, tonic convulsion, ptosis, mydriasis, lacrimation, epistaxis, diarrhoea, cold extremities and vocalisation on handling occurred in individual animals.
Ante mortem general loss of reflexes and dyspnoea were observed.
Symptoms of toxicity were observed 3 minutes after substance administration and generally lasted up to one day (epistaxis up to 4 days after administration).
Body weight:
No effects on body weight noted
Gross pathology:
Observations at necropsy included: tympany in the stomach, red stomach and intestinal mucous membranes, liquid-filled intestine, red discolouration in the intestine of individual animals, red spotted/marbled lung of emphysematous consistency, reddened peritoneum, pancreas, spleen and external skin in individual animals.
Other findings:
- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: no data

The slopes of the dose response curves were:

Males: 4.6 (95% CL 0.8 - 8.4)

Females: 5.1 (95% CL 1.2 - 9.0)

Males and females: 2.9 (95% CL 0.9 - 4 .9)

Interpretation of results:
Category 2 based on GHS criteria
Conclusions:
In a study performed in accordance with OECD Test Guideline 401 (acute oral toxicity) but not in compliance with GLP, triethoxy(3-thiocyanatopropyl)silane was harmful when administered via oral gavage to rats, with acute oral LD50s of 986 (male), 1650 (female) and 1423 mg/kg bw (males and females) calculated.
Executive summary:

An acute oral study was carried out according to OECD Test Guideline 401 (acute oral toxicity), in which male and female Wistar rats were exposed to triethoxy(3-thiocyanatopropyl)silane via oral gavage.

 

Generally, groups of five males and five females were given a single oral gavage administration of triethoxy(3-thiocyanatopropyl)silane (in peanut oil) at 464, 681, 1000, 1470 or 2150 mg/kg bw, and observed for 14 days (ten females were given 1000 mg/kg bw, and no males were treated with 2150 mg/kg bw). After the observation period, surviving animals were sacrificed. Both sacrificed animals and those dying over the course of the experiment were subject to gross necropsy.

 

Overt signs of toxicity included hypokinesia (decreased body movement), clonic convulsions, decrease of muscle tone, salivation and strenuous breathing. Adverse effects on the stomach, intestines and lungs were noted at necropsy (the peritoneum, pancreas, spleen and skin were also affected in individual animals). There was no noted effect on body weight. Over the course of the study, mortality was observed in individuals belonging to each treatment group between 0.5 and 24 hours after administration.

Under the conditions of this study, triethoxy(3-thiocyanatopropyl)silane was harmful to rats. LD50 values were calculated for males (986 mg/kg bw), females (1650 mg/kg bw) and male and female animals (1423 mg/kg bw).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 423 mg/kg bw

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
Study period:
29 September 2011 to 18 October 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / The Netherlands
- Age at study initiation: 9 weeks (males), 11 weeks (females)
- Weight at study initiation: 225.1 to 234.5 g (males), 201.3 to 216.2 g (females)
- Fasting period before study: no data
- Housing: in groups of three in Makrolon type 4 cages
- Diet (e.g. ad libitum): pellet diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 ± 3
- Humidity (%): 30 to 70
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29 September 2011 To: 18 October 2011
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: ~ 5 x 5 cm
- % coverage: 10
- Type of wrap if used: gauze pad held in place by adhesive hypoallergenic aerated dressing and elastic adhesive restrainer bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 ml/kg bw
- Constant volume or concentration used: no
Duration of exposure:
24 h
Doses:
4000 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: 15 days (day of treatment (day 1) and up until 14 days after patch removal (days 2 to 15))
- Frequency of observations and weighing: Clinical signs and mortality assessed within first 30 minutes and 1, 2, 3 and 5 hours after treatment, and on days 2 to 15 (daily for clinical signs, twice daily for mortality). Skin observed daily during test days 2 to 15 (re-clipped on days 4, 8, 10 and 14). Body weights recorded on day 1 (prior to treatment), 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality observed throughout the study
Mortality:
There were no deaths over the course of the study.
Clinical signs:
Slightly increased activity noted in all males and females 1 and 2 hours after treatment on day 1.
5 hours after treatment, dragging of limbs seen in all animals and still seen on day 2 in all males and four females, persisting up to day 3 in two males.
Slight/moderately decreased activity noted on day 2 and/or 3.
Severely decreased activity on day 2 in one female, with decreased severity (slight) noted on day 4. Also reduced temperature, vocalisation and shivering noted on day 2 in this animal.
Body weight:
No effects on body weight were reported.
Gross pathology:
No macroscopic findings recorded at necropsy.
Other findings:
- Other observations: Slight erythema was seen in four males during the first days after treatment. Focal crusts were additionally seen in three of these males and slight desquamation in one. All these symptoms reverted by day 8. Slight to moderate erythema in females, persisting up until day 13/14 in two animals. Slight to severe focal crusts were seen in all animals, and persisted in two females up until test day 15. Slight to severe desquamation was seen in four females, and slight to moderate necrosis in two females. In one female, desquamation was still seen at day 15.
Interpretation of results:
GHS criteria not met
Conclusions:
In a study carried out in accordance with OECD Test Guideline 402 and in compliance with GLP, triethoxy(3-thiocyanatopropyl)silane was of low toxicity to rats following a 24-hour dermal application. The acute dermal LD50 was determined to be greater than 4000 mg/kg bw.
Executive summary:

In a GLP-compliant study carried out in accordance with OECD Test Guideline 402, triethoxy(3-thiocyanatopropyl)silane was assessed for its dermal toxicity in rats.

The test material was applied semi-occlusive to the clipped skin of five male and five female Wistar rats at 4000 mg/kg bw for 24 hours (day 1). Rats were then observed for clinical signs of toxicity and mortality for a further 14 days (days 2 to 15), before sacrifice and gross necropsy.

 

No mortality occurred and no significant gross macroscopic or body weight changes were reported. Dragging of limbs was noted in all animals within a day of application. This persisted until day two in females except from one female and to day three in two males. A sigificant increased activity was observed in all animals shortly after treatment, while decreased activity was noted on days two and three. More severe effects (severely decreased activity, reduced temperature, vocalisation and shivering) were observed in one female on day two.

 

Some males demonstrated reversible skin effects (slight erythema and focal crusts, with slight desquamation in one), which reverted within eight days of application. Skin effects were more pronounced in females (slight to moderate erythema, slight to severe focal crusts, slight to severe desquamation, and slight to moderate necrosis), with some effects lasting up until day 15 (focal crusts in two animals, desquamation in one).

 

Triethoxy(3-thiocyanatopropyl)silane was of low systemic toxicity when applied to the skin of male and female rats for 24 hours. The acute dermal LD50 was determined to be greater than 4000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
4 000 mg/kg bw

Additional information

The key study for acute oral toxicity, conducted according to OECD test guideline 401 but not in compliance with GLP, reports an LD50 value of 1423 mg/kg bw in rat (males and females) (ASTA Pharma 1987). Signs of toxicity included hypokinesia, clinic convulsions, decrease of muscle tone, salivation and strenuous breathing. Stilted gait, tonic convulsion, ptosis, mydriasis, lacrimation, epistaxis, diarrhoea, cold extremities and vocalisation on handling also occurred in individual animals. Ante mortem general loss of reflexes and dyspnoea were observed. Symptoms of toxicity were observed 3 minutes after substance administration and generally lasted up to one day (epistaxis up to 4 days after administration). Observations at necropsy included: tympany in the stomach, red stomach and intestinal mucous membranes, liquid-filled intestine, red discolouration in the intestine of individual animals, red spotted/marbled lung of emphysematous consistency, reddened peritoneum, pancreas, spleen and external skin in individual animals.

An acute dermal toxicity study was carried out in compliance with GLP and in accordance with OECD 402, in which triethoxy(3-thiocyanatopropyl)silane was found to be of low toxicity to rats following a 24-hour dermal application (Harlan 2011). The acute dermal LD50 was determined to be greater than 4000 mg/kg bw. There were no deaths over the course of the study, and no significant gross macroscopic or body weight changes were reported. Dragging of limbs was noted in all animals within a day of application and persisted in all but one (a female) until day two, and to day three in two males. Activity was significantly increased in all animals shortly after treatment, while decreased activity was noted on days two and three. More severe effects (severely decreased activity, reduced temperature, vocalisation and shivering) were seen in one female on day two. Some males demonstrated reversible skin effects (slight erythema and focal crusts, with slight desquamation in one), which reverted within eight days of application. Skin effects were more pronounced in females (slight to moderate erythema, slight to severe focal crusts, slight to severe desquamation, and slight to moderate necrosis), with some effects lasting up until day 15 (focal crusts in two animals, desquamation in one).

Justification for classification or non-classification

Based on the available information, no classification is required for acute dermal toxicity. However, the reported acute oral LD50 value of 1423 mg/kg bw in male and female rats requires classification of triethoxy(3-thiocyanatopropyl)silane as Category 4, H302; Harmful if swallowed in accordance with Regulation (EC) No 1272/2008.