N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine

Endpoint summary

Description of key information

Oral (OECD 423), rat: LD50 cut-off = 2500 mg/kg bw

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:

29 June to 21 July 2022

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

Dec 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit, Schwabach, Germany

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han) (full barrier)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Step 1: 8 - 9 weeks; Step 2: 9 - 10 weeks
- Weight at study initiation: Step 1: 155 - 167 g; Step 2: 166 - 176 g
- Fasting period before study: yes, prior to the administration food was withheld from the test animals for 16 to 18 hours (access to water was permitted). Food was provided again approximately 3 hours post dosing.
- Housing: group housed in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding.
- Diet: Altromin 1324 maintenance diet for rats and mice (Altromin Spezialfutter GmbH & Co. KG, Lage, Germany), ad libitum.
- Water: tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals), ad libitum.
- Acclimation period: Step 1: 6 days; Step 2: 13 days

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

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

2000 mg/kg bw (Step 1 and Step 2)

No. of animals per sex per dose:

Step 1: 3 females at 2000 mg/kg bw
Step 2: 3 females at 2000 mg/kg bw

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: a careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
The animals were weighed on Day 1 (prior to the administration) and on Days 8 and 15.
- Clinical signs: cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

2 500 mg/kg bw

Based on:

test mat.

Mortality:

Step 1: one animal was found dead on the day of treatment (5.5 hours post-dose).
Step 2: one animal was found dead on the day of treatment (3 hours post-dose).

See Table 3 for details of the LD50 cut-off value.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

None of the animals showed weight loss during the observation period (see Table 2 for details).

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Table 1: Clinical Signs - Individual Data

Step	Animal No. / Sex	Starting Dose (mg/kg bw)	Time of Observation	Observations
1	1, 2 / female	2000	0 min – Day 15	nsf
	3 / female	2000	0 min – 240 min	nsf
			334 min	Animal found dead
2	4 / female	2000	0 min – 30 min	nsf
			30 min – 60 min	Reduced spontaneous activity (slight), prone position, shallow breathing
			60 min – 180 min	Reduced spontaneous activity (moderate), prone position, ataxia (slight), half eyelid closure, shallow breathing
			180 min – 240 min	Reduced spontaneous activity (slight), wasp waist, piloerection (slight)
			240 min – Day 2	Reduced spontaneous activity (slight), hunched posture, piloerection (moderate)
			Day 2 – Day 15	nsf
	5 / female	2000	0 min – 30 min	nsf
			30 min – 120 min	Reduced spontaneous activity (slight)
			120 min – 180 min	Reduced spontaneous activity (moderate), prone position, ataxia (slight), wasp waist, half eyelid closure, shallow breathing
			180 min	Animal found dead
2	6 / female	2000	0 min – 30 min	nsf
			30 min – 60 min	Reduced spontaneous activity (slight)
			60 min – 120 min	Reduced spontaneous activity (moderate), ataxia (slight), prone position, half eyelid closure, shallow breathing
			120 min – 180 min	Piloerection (slight)
			180 min – 240 min	Reduced spontaneous activity (slight), piloerection (slight)
			240 min – Day 2	Reduced spontaneous activity (slight), hunched posture, piloerection (moderate)
			Day 2 – Day 15	nsf

Day = study day (study Day 1 = day of administration); min = minute(s) post-application; nsf = no specific findings

Based on these results and according to the acute toxic class method regime no further testing was required. Therefore, according to OECD Guideline 423, a sufficient estimation of the acute oral toxicity of the test item is provided

 

Table 2: Absolute Body Weights (g) and Body Weight Change (%)

Step	Animal No. / Sex	Starting Dose (mg/kg bw)	Body Weight (g)			Body Weight Change in Comparison to Day 1 (%)
			Day 1	Day 2	Day 3
1	1 / Female	2000	162	184	190	17
	2 / Female		155	186	194	25
	3 / Female		167	n.a.	n.a.	-
2	4 / Female	2000	166	188	198	19
	5 / Female		169	n.a.	n.a.	-
	6 / Female		176	200	209	19

n.a. = not applicable (animals found dead on Day 1)

 

Table 3: LD50 Cut-Off Value

Starting Dose (mg/kg bw)	Number of Animals	Number of Intercurrent Deaths	LD50 Cut-Off (mg/kg bw)
2000	6	2	2500

Interpretation of results:

other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No. 1272/2008

Conclusions:

The acute oral toxicity study was conducted according to OECD 423 and in compliance with GLP. Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg bw. The liquid test item was administered undiluted. One animal of the first step was found dead on the day of the treatment (5.5 hours post-dose). The remaining two animals survived until the end of the study. No test item-related signs of toxicity were observed in any of the animals of Step 1. One animal of the second step was found dead on the day of the treatment (3 hours post-dose). The remaining animals of the step survived until the end of the study. Test item-related signs of toxicity were observed in all animals of Step 2. Based on the results, a LD50 cut-off value of 2500 mg/kg bw was derived.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

An acute oral toxicity study is available with N-{3-[dimethoxy(methyl)silyl]propyl}butan-1-amine (CAS 120939-52-8), which was conducted according to OECD 423 and in compliance with GLP (BSL, 2023).

Two groups, each of three fasted female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg bw. The liquid test item was applied undiluted. All animals used in the study were allowed to acclimatise to the laboratory conditions for at least 6 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the 14-day observation period. Body weights were recorded on Day 1 (prior to the administration) and on Days 8 and 15. All animals were necropsied and examined macroscopically.

One animal of the first step treated with the test item at a dose of 2000 mg/kg bw was found dead on the day of the treatment (5.5 hours post-dose). The remaining animals of the step survived until the end of the study. No test item-related signs of toxicity were observed in any of the animals of Step 1.

One animal of the second step treated with the test item at a dose of 2000 mg/kg bw was found dead on the day of the treatment (3 hours post-dose). The remaining animals of the step survived until the end of the study. Test item-related signs of toxicity were observed in all animals of Step 2. The most relevant clinical findings were reduced spontaneous activity, prone position, ataxia, wasp waist, hunched posture, piloerection, half eyelid closure and abnormal breathing. The surviving animals recovered within one day post-dose.

Throughout the 14-day observation period, the weight gain of the surviving animals was within the normal range of variation for this strain.

At necropsy, no macroscopic findings were observed in the surviving or decedent animals.

Under the conditions of the study, a LD50 cut-off value of 2500 mg/kg bw was derived.

Justification for classification or non-classification

The available data on acute oral toxicity of the test substance does not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and is therefore conclusive but not sufficient for classification.

No data are available for acute inhalation or dermal toxicity.