reaction mass of 1-chloro-3-(dodecyloxy)propan-2-ol andalpha-dodecyl-omega-hydroxy-di[oxy[(chloromethyl)-1,2-ethanediyl]] andalpha-dodecyl-omega-hydroxy-tri[oxy[(chloromethyl)-1,2-ethanediyl]]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 November 2006 - 10 December 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in compliance with OECD Guideline 423 without any deviation.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

reaction mass of 1-chloro-3-(dodecyloxy)propan-2-ol and alpha-dodecyl-omega-hydroxy-di[oxy[(chloromethyl)-1,2-ethanediyl]] and alpha-dodecyl-omega-hydroxy-tri[oxy[(chloromethyl)-1,2-ethanediyl]]

Cas Number:

63727-39-9

Molecular formula:

C15H31ClO2 C18H36Cl2O3 C21H41Cl3O4

IUPAC Name:

reaction mass of 1-chloro-3-(dodecyloxy)propan-2-ol and alpha-dodecyl-omega-hydroxy-di[oxy[(chloromethyl)-1,2-ethanediyl]] and alpha-dodecyl-omega-hydroxy-tri[oxy[(chloromethyl)-1,2-ethanediyl]]

Test material form:

other: liquid

Details on test material:

- Physical state: Thick colorless to pale yellow liquid
- Date of receipt: 12 October 2006
- Expiration date of the lot/batch: 04 October 2007
- Storage condition of test material: Room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: 202 ± 7 g
- Fasting period before study: Animals were fasted for an overnight period of approximately 18 h before dosing, but had free access to water. Food was given back approximately 4 h after administration of the test item.
- Housing: Animals were housed in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals during the acclimation period and three rats of the same group during the treatment period.
- Diet: SSNIFF R/M-H pelleted diet (SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: Drinking water filtered by a FG Millipore membrane (0.22 micron), ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 30-70 %
- Air changes: Approximately 12 cycles/h of filtered, non-recycled air
- Photoperiod: 12 h dark / 12 h light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Justification for choice of vehicle: As the test item was not soluble in purified water, corn oil was used as the vehicle (solution).
- Lot/batch no. (if required): 015K015 (Sigma, Saint-Quentin-Fallavier, France)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION:
- The test item was prepared at the chosen concentrations in the vehicle. The test item preparation was made freshly on the morning of administration.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose-level used as the starting dose-level was selected from one of four fixed levels, 5, 50, 300 and 2000 mg/kg bw. As no information on the toxic potential of the test item was available, for animal welfare reasons, the starting dose-level of 300 mg/kg bw was chosen.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

- First assay: 3 females/dose (300 mg/kg bw)
- Second assay: 3 females/dose (2000 mg/kg bw)
- Confirmatory assay: 3 females (2000 mg/kg bw)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical signs and mortality: Animals were observed frequently during the hours following administration of the test item, for detection of possible treatment-related clinical signs. Thereafter, observation of the animals was made at least once a day.
- Bodyweight: Animals were weighed individually just before administration of the test item on Day 1 and then on Days 8 and 15.
- Necropsy of survivors performed: Yes; On day 15, all animals were killed by carbon dioxide asphyxiation and macroscopic examination was performed.

Statistics:

None

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed.

Mortality:

- No mortality was observed.

Clinical signs:

- No clinical signs were observed at 300 mg/kg bw.
- At 2000 mg/kg bw, hypoactivity (all the animals), piloerection and dyspnea (3/6 animals) were observed within 4 h of treatment.

Body weight:

- When compared to historical control animals, a slightly lower body weight gain was recorded in 2/6 females treated at 2000 mg/kg bw between Days 1-8, and in 1/3 females treated at 300 mg/kg bw between Days 8-15, without any relevant consequence at the end of the observation period.
- Overall body weight gain of the other animals was not affected by treatment with the test item.

Gross pathology:

- No macroscopic abnormalities were observed at necropsy.

Other findings:

None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the oral LD50 of the test item is higher than 2000 mg/kg bw in female rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).

Executive summary:

In a GLP-compliant acute oral toxicity study performed according to OECD Guideline 423, groups of Sprague Dawley [Rj:SD (IOPS Han)] rats (3 females/dose) were given a single oral (gavage) dose of the test item at 300 and 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

No mortality and no clinical signs were observed at 300 mg/kg bw. At 2000 mg/kg bw, no mortality was observed. However, hypoactivity (all the animals), piloerection and dyspnea (3/6 animals) were observed within 4 h of treatment. When compared to historical control animals, a slightly lower body weight gain was recorded in 2/6 females treated at 2000 mg/kg bw between Days 1-8, and in 1/3 females treated at 300 mg/kg bw between Days 8-15, without any relevant consequence at the end of the observation period. Overall body weight gain of the other animals was not affected by treatment with the test item. No macroscopic abnormalities were observed at study termination. The oral LD50 of the test item 75418/10 was therefore considered to be higher than 2000 mg/kg bw in female rats.

Under the test conditions, the oral LD50 of the test item is higher than 2000 mg/kg bw in female rats; it is therefore not classified according to the Annex VI to the Directive 67/548/EEC and to the CLP Regulation (EC) N° (1272-2008).