1,3-Propanediol, 2-methyl-, reaction products with ethenyltrimethoxysilane

Endpoint summary

Description of key information

Oral (OECD 423), rat (f): LD50 > 5000 mg/kg bw (limit test)
Dermal (OECD 402), rat (m/f): LD50 > 2000 mg/kg bw (limit test)

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:

30 Mar - 22 Apr 2010

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: RccHan: WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories B.V., NM Horst, The Netherlands
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 175.7-189.4 g
- Fasting period before study: animals were fasted prior to test substance administration for approximately 16 to 18 h. Food was provided again approximately 3 h after dosing.
- Housing: animals were housed in groups of 3 in Makrolon type-4 cages with wire mesh tops and standard softwood bedding (‘Lignocel’ J. Rettenmaier & Söhne GmbH & Co KG, Rosenberg, Germany).
- Diet: pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 83/09 (Provimi Kliba AG, Kaiseraugst, Switzerland), ad libitum
- Water: community tap water from Füllinsdorf, Switzerland, ad libitum
- Acclimation period: at least 5 days

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

IN-LIFE DATES: From: 06 Apr 2010 (group 1) or 08 Apr 2010 (group 2) To: 20 Apr 2010 (group 1) 22 Apr 2010 (group 2)

Route of administration:

oral: gavage

Vehicle:

other: polyethylene glycol 300 (PEG 300)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20% (w/w)
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: in a preliminary solubility test, the test substance was well dissolved in PEG 300.
- Lot/batch no.: S60502-099

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 in group 1 and group 2, respectively

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical signs and mortality once before treatment, within the first 30 min and at approximately 1, 2, 3 and 5 h after treatment on Day 1. During the observation period, animals were observed twice daily for mortality and once daily for clinical signs. Body weights were recorded on Day 1 (prior to administration) and on Days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: experimental result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off according to OECD 423

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: Slightly ruffled fur was observed in all 6 animals 2 h after test substance administration. The ruffled fur persisted with the same severity in 2 animals of group 2 at the 3 h reading. All 6 animals of groups 1 and 2 were free of clinical signs from the 5

Gross pathology:

No macroscopic findings were recorded at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of a reliable acute toxicity study Y-15866 is not classified for acute oral toxicity.

Executive summary:

The acute oral toxicity of Y-15866 was investigated in a GLP-conform study according to the acute toxic class method (OECD guideline 423). Two groups, each consisting of 3 female RccHan:WIST rats, were treated with Y-15866 diluted in PEG 300 as vehicle by single oral gavage administration at a limit dose of 2000 mg/kg bw. The animals were observed for clinical signs and mortality once before treatment, within the first 30 min and at approximately 1, 2, 3 and 5 h after treatment on Day 1. During the observation period of 14 days, animals were inspected twice daily for mortality and once daily for clinical signs. Body weights were recorded on Day 1 (prior to administration) and on Days 8 and 15. All animals were necropsied and examined macroscopically. No mortality occurred during the study period. Slightly ruffled fur was observed in all 6 animals 2 h after test substance administration. The ruffled fur persisted with the same severity in 2 animals at the 3 h reading. All 6 animals of groups 1 and 2 were free of clinical signs from the 5 h reading to the end of the study (on Day 15). The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. Based on these experimental results, the LD50 of Y-15866 was greater than 2000 mg/kg bw. According to the criteria of OECD guideline 423, the LD50 cut-off of Y-15866 may be considered to be greater than 5000 mg/kg bw.

Endpoint conclusion

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

The available study is reliable (Klimisch 1).

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:

30 Mar - 20 Apr 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: RccHan: WIST

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

other: polyethylene glycol 300 (PEG 300)

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of a reliable acute toxicity study Y-15866 is not classified for acute dermal toxicity.

Executive summary:

The acute dermal toxicity of Y-15866 was tested in accordance with OECD guideline 402 and in compliance with GLP. The study was performed as a limit test in RccHan: WIST rats (5 males and 5 females) at a dose of 2000 mg/kg bw. The test substance was applied at a concentration of 50% (w/w) in polyethylene glycol 300 (PEG 300) onto the clipped skin of the test animals for 24 h under semiocclusive conditions. After removal of the test substance, animals were observed for a period of 14 days. No local dermal signs were noted during the course of the study with the exception of one male, which showed very slight erythema at the application site on Day 2 after treatment. No mortalities and no signs of systemic toxicity were observed. The body weight evolution in all animals was not affected by treatment. No macroscopic findings were recorded at necropsy. Based on these results, the dermal LD50 value for male and female rats was greater than 2000 mg/kg bw.

Endpoint conclusion

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available study is reliable (Klimisch 1).

Additional information

Oral

The acute oral toxicity of Y-15866 was investigated in a GLP-conform study according to the acute toxic class method (OECD guideline 423). Two groups, each consisting of 3 female RccHan:WIST rats, were treated with Y-15866 diluted in PEG 300 as vehicle by single oral gavage administration at a limit dose of 2000 mg/kg bw (Arcelin, 2010). No mortality occurred during the study period. Slightly ruffled fur was observed in all 6 animals 2 h after test substance administration. The ruffled fur persisted with the same severity in 2 animals at the 3 h reading. All 6 animals were free of clinical signs from the 5 h reading to the end of the study (on Day 15). No effects on body weights were observed and necropsy revealed no substance-related findings. Based on these experimental results, the LD50 of Y-15866 was greater than 2000 mg/kg bw. According to the criteria of OECD guideline 423, the LD50 cut-off of Y-15866 may be considered to be greater than 5000 mg/kg bw.

Dermal

The acute dermal toxicity of Y-15866 was tested in accordance with OECD guideline 402 and in compliance with GLP (Arcelin, 2011). The study was performed as a limit test in RccHan: WIST rats (5 males and 5 females) at a dose of 2000 mg/kg bw. The test substance was applied at a concentration of 50% (w/w) in polyethylene glycol 300 (PEG 300) onto the clipped skin of the test animals for 24 h under semiocclusive conditions. After removal of the test substance, animals were observed for a period of 14 days. No local dermal signs were noted during the course of the study with the exception of one male, which showed very slight erythema at the application site on Day 2 after treatment. No mortalities and no signs of systemic toxicity were observed. The body weight evolution in all animals was not affected by treatment. No macroscopic findings were recorded at necropsy. Based on these results, the dermal LD50 value for male and female rats was greater than 2000 mg/kg bw.

Justification for classification or non-classification

The available data on the acute toxicity of Y-15866 do not meet the criteria for classification according to Regulation (EC) 1272/2008 (CLP) or Directive 67/548/EEC (DSD), and are therefore conclusive but not sufficient for classification.