Registration Dossier

Administrative data

Description of key information

The key acute oral and dermal studies are the only available data for the registered substance for these endpoints (BRRC, 1980a and 1980c) and identified LD50 values of 3010 and 11460 mg/kg respectively. The studies were carried out according to protocols that were similar to appropriate OECD test guidelines, but pre-dated GLP, and were therefore assigned reliability 2. No reliable acute inhalation data are available for the registered substance. However, in the same study as the key acute oral and dermal data were reported, there were no mortalities among rats exposed to substantially saturated vapour for 6 hours.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Study predates GLP but is sufficiently documented, meets generally accepted scientific principles and is acceptable for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
No follow up study in females; limited details of clinical examinations and pathology,
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no details
- Age at study initiation: 3-4 wk
- Weight at study initiation: 90-120 g
- Fasting period before study: no details
- Housing: no details
- Diet: standard diet ad libitum
- Water: drinking water ad libitum
- Acclimation period: no details

ENVIRONMENTAL CONDITIONS
no details

IN-LIFE DATES: no details
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg bw (neat test substance)
Doses:
1.25, 2.5, 5.0 ml/kg bw
No. of animals per sex per dose:
5 males/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighed at days 0 and 14; no details on frequency of observations
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Moving average method.
Sex:
male
Dose descriptor:
LD50
Effect level:
2.97 mL/kg bw
95% CL:
>= 1.67 - <= 5.28
Remarks on result:
other: approximately 3030 mg/kg bw.
Mortality:
See table 1.
Clinical signs:
See table 1.
Body weight:
See table 1.
Gross pathology:
Among the survivors at 2.5 ml/kg bw, the rat with weight loss (see table 1) had pus in the lungs. No other remarkable findings in survivors. Those that died had purple colouration in the glandular stomach.

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)

Overt toxicity

Weight change (g)

Male

1.25

0/5

-

-

 75 to 107 (mean 95)

2.5

2/5

0,5

Sluggish @ 10 mins; one death @ 15 mins.

 -31 to 108 (mean 61)

5.0

4/5

0,0,0,5

Sluggish and unsteady gait @ 2 mins; salivation @ 10 mins; death of 3 @ 6 min-2.5 h.

 125

 

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Not classified based on EU criteria
Conclusions:
A brief summary of a limited study, conducted according to a protocol that was similar to guideline but not compliant with GLP, recorded an LD50 in the rat of 2.97 ml/kg bw (approximately 3030 mg/kg bw).
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
3 010 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study predates GLP but is sufficiently documented, meets generally accepted scientific principles and is acceptable for assessment.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Only 4 males tested at each dose; no follow-up assessment in females. Occlusive covering. Limited detail of clinical examinations and pathology.
GLP compliance:
no
Test type:
standard acute method
Species:
rabbit
Strain:
New Zealand White
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no details
- Age at study initiation: 3-5 months
- Weight at study initiation: no details
- Fasting period before study: no details
- Housing: no details
- Diet (e.g. ad libitum): no details
- Water (e.g. ad libitum): no details
- Acclimation period: no details

ENVIRONMENTAL CONDITIONS
no details

IN-LIFE DATES: no details
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: no details
- % coverage: no details
- Type of wrap if used: polyethylene

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test substance 'removed' after exposure
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4, 8 and 16 ml/kg bw (no further details).
- Concentration (if solution): neat
Duration of exposure:
24 h
Doses:
4, 8 and 16 ml/kg bw
No. of animals per sex per dose:
4 males/dose
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no details
- Necropsy of survivors performed: apparently yes - very limited details given
- Other examinations performed: body weight - very limited details given
Sex:
male
Dose descriptor:
LD50
Effect level:
11.3 mL/kg bw
95% CL:
5.19 - 24.7
Mortality:
See table 1.
Clinical signs:
None reported.
Body weight:
See table 1; no further details given.
Gross pathology:
See table 1; no further details given.
Other findings:
- Organ weights: not measured
- Histopathology: see table 1
- Potential target organs: insufficient detail available

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)

Local skin effects

Pathology

Body weight change (g)

[as reported – initial body weight not given]

4

0/2

-

Scabbing in1 of 2 on day 14

In fatalities: discoloured liver  (mottled red and tan, white spots) and kidneys (tan).

In survivors: discoloured livers (dark red) and kidneys (mottled tan and red).

4; 61

8

1/4

9

Erythema, oedema, desquamation and necrosis; full details not presented.

-784 to 239 (mean 239)

16*

3/4

1, 2, 4

Erythema, oedema, desquamation, necrosis and fissuring in the survivor; full details not presented.

59

* two different samples of test substance used for 2 rabbits in each case

Interpretation of results:
GHS criteria not met
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
A brief summary of a limited study, for which neither guideline nor GLP status were reported, recorded an LD50 in the rabbit of 11.3 ml/kg bw.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
11 460 mg/kg bw

Additional information

In the key acute oral toxicity study (BRRC, 1980a), an LD50 value 2.97 ml/kg was determined for male rats in a study that was carried out according to a protocol that was similar to OECD 401 but was not compliant with GLP. Clinical signs included sluggishness and unsteady gait. Necropsy of animals that died during the study revealed purple-coloured glandular portions of the stomach. Based on a relative density of 1.014, the LD50 was approximately 3010 mg/kg bw.

In the key acute dermal toxicity study (BRRC, 1980c), an LD50 value of 11.3 ml/kg was determined for rabbits in a study that was carried out according to a protocol that was similar to OECD 402 but was not compliant with GLP. No clinical signs were reported, but severe local effects were observed at the higher dose levels of 8 and 16 ml/kg. In fatalities, necropsy findings were discoloured liver (mottled red and tan, white spots) and kidneys (tan). In survivors, discoloured livers (dark red) and kidneys (mottled tan and red). Based on a relative density of 1.014, the LD50 was approximately 11460 mg/kg bw.




Justification for classification or non-classification

Based on the available data for the oral, inhalation and dermal routes, 3-(trimethoxysilyl)propylamine does not require classification for acute toxicity according to Regulation (EC) 1272/2008.