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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 August 2011 - 12 October 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011

Materials and methods

Test guidelineopen allclose all
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 (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
dodecane-12-lactam, manufacturing of, by-products from, distillation residues
EC Number:
923-400-5
IUPAC Name:
dodecane-12-lactam, manufacturing of, by-products from, distillation residues
Test material form:
solid
Details on test material:
- Name of test material: Dodecane-12-Lactam Manufacturing of, by-products from, distillation residues
- Physical state: brown solid
- Lot/batch No.: AVRIL 2011
- Expiry date: 30 April 2012
- Composition of test material: UVCB
- Storage condition: at room temperature.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: on the day of treatment, the females were approximately 8 weeks old
- Mean body weight at study initiation: 212 g (range: 195 g to 228 g)
- Fasting period before study: yes, during the night before treatment
- Housing: polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 6 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

IN-LIFE DATES: 14 September 2011 to 12 October 2011

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5% methylcellulose aqueous solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: in the absence of recommendation from the Sponsor, the solubility assay first started at the concentration of 200 mg/mL, and the first choice vehicle was drinking water treated by reverse osmosis.
As unsatisfactory solubility of the test item was obtained in this vehicle, 0.5% methylcellulose aqueous solution, batch Nos. 107K0081 and 066K0129, supplied by Sigma (Saint-Quentin-Fallavier, France) was used. A homogenous suspension was obtained at the concentration of 200 mg/mL in 0.5% methylcellulose aqueous solution.

DOSAGE PREPARATION (if unusual):
The test item was administered as a homogenous suspension in the vehicle.
The test item was ground to a fine powder, using a mortar and pestle, and then mixed with the required quantity of vehicle.
Dosage form preparations were prepared by the CIT Pharmacy extemporaneously on the day of each administration.
The dosage forms were stored at room temperature, and delivered to the study room in brown flasks.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose:
The starting dose-level was selected in agreement with the Sponsor. Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data have been taken into account by the Sponsor; the starting dose level was 300 mg/kg for animal welfare reasons.
After treatment at the starting dose-level, the next dose-levels were administered in a sequential manner, under the same conditions to different
animals, according to the flow charts of OECD Guideline No. 423, 17th December 2001, which are equivalent to those of Commission Regulation (EC) No. 440/2008, B.1tris (30 May 2008).
Doses:
300 and 2000 mg/kg.
No. of animals per sex per dose:
3 per treatment step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No unscheduled deaths occurred in any animals.
Clinical signs:
No clincal signs at 300 mg/kg/day.
At 2000 mg/kg, hypoactivity, lateral/ventral recumbency and sedation were observed in almost all animals, accompanied in some females byhunched posture, staggering gait, half-closed eyes, ptyalism, tremors and/or dyspnea.
Body weight:
No effects on body weight were recorded, except in one animal during the first week of the study.
Gross pathology:
none.
Other findings:
none.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of the test item was higher than 2000 mg/kg in rats.
Therefore, the test item is not classified as toxic by oral route according to the criteria of CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential acute toxicity of the test item following a single oral administration (gavage) to rats.

This study was conducted in compliance with the principles of Good Laboratory Practice and according to OECD 423 guideline.

 The test item was administered once by oral route (gavage) to three groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test item was prepared in a 0.5% solution of methylcellulose.

Since no relevant toxicity data are available for the estimation of a lethal dose-level and any existing data have been taken into account by the Sponsor, the starting dose-level was 300 mg/kg for animal welfare reasons.After the first assay, the next higher dose-level of 2000 mg/kg was tested. Then, as no toxicity was observed at this higher dose-level, the results were confirmed in other females.

No unscheduled deaths occurred in any animals. No clinical signs were observed at 300 mg/kg.At 2000 mg/kg, hypoactivity, lateral/ventral recumbency and sedation were observed in almost all animals, accompanied in some females byhunched posture, staggering gait, half-closed eyes, ptyalism, tremors and/or dyspnea. These clinical signs were either limited to the day of administration or lasted until day 5.

No effects on body weight were recorded, except in one animal during the first week of the study and there were no macroscopic post-mortem findings.

Conclusion

The oral LD50of the test item was higher than 2000 mg/kg in rats. 

Therefore, the test item is not classified as toxic by oral route according to the criteria of CLP Regulation.

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