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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
January 18, 1999 - January 20, 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guidlines for Testing of Chemicals Section 4: Health Effects, No. 401 (1987) and Commission Directive 92/69/EEC Annex V - Method B1 (1992) test procedures used.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
yes
Remarks:
The study was conducted using valid GLP
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Reference substance name:
Nitric acid, reaction products with cyclododecanol and cyclododecanone, by-products from, high-boiling fraction
EC Number:
276-431-5
EC Name:
Nitric acid, reaction products with cyclododecanol and cyclododecanone, by-products from, high-boiling fraction
Cas Number:
72162-23-3
Molecular formula:
UVCB substance. Formula not available
IUPAC Name:
Not available for a UVCB
Details on test material:
-Name of test material (as cited in study report): Corfree M1
-Physical state: solid
-Impurities (identity and concentrations): no data
-Purity test date: no data
-Expiration date of lot/batch: no data
- Stability under test conditions: no evidence of instability was observed.
-Storage condition of test material: no data
-Other: no additional data





Test animals

Species:
rat
Strain:
other: CrlCD(SD)IGS BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc. Raleigh, North Carolina
- Age at study initiation: malerats were 57 days old and the female rats were 78 days old at the day of dosing.
- Weight at study initiation: males 223.3g (average), female 206.1g (average)
- Fasting period before study: 20.5 hours
- Housing: singly in suspended, stainless steel, wire-mesh cages. An animal health monitoring program was in place.
- Diet (e.g. ad libitum): PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 food ad libitumexcept 20.5 hours before study
- Water (e.g. ad libitum): ad libitum except a 20.5 hours diet before treatment
- Acclimation period: Rats were quarantined, weighted, and observed for general health for 6 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23° ± 1°C
- Humidity (%): 50 ± 10%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark cycle

Administration / exposure

Route of administration:
other: intragastric intubation
Vehicle:
other: acetone and deionized water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 300 mg/mL, average dose volume 3.7 ml (male), 3.4 ml (female)
- Amount of vehicle (if gavage): approximately 15% acetone
- Justification for choice of vehicle: Attempts to mix the test substance with deionized water or corn oil failed due to insolubility of test substance in these vehicles.
- Lot/batch no. (if required): no data
- Purity: no data


MAXIMUM DOSE VOLUME APPLIED: 700 mg/kg = 14.0 mL/kg


DOSAGE PREPARATION (if unusual): The acetone and test substance were mixed by hand until all the test substance was moistened. Deionized water was added to the 30ml mark of the 50ml graduated cylinder, and the solution was mixed by hand. The solution was mixed with a polytron until it appeared smooth and the test substance appeared homogeneously distributed.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: To determine that the lethal dose 50 was greater than 5000 mg/kg the dose was selected.
Doses:
5,000 mg/kg
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
not specified
Details on study design:
-Duration of obsevation period following administration: 14 days
-Frequency of observations and weighting: daily mortality checks and body weight determinations and observations for clinical signs of toxicity (1 weekend excluded).
-Necropsy of survivors performed: yes
-Other examinations performed: clinical signs, body weight
Statistics:
standard deivations are given in the report, but the method is not directly wrriten in the study.

Results and discussion

Preliminary study:
In a preliminary study, Corfree® M1 was administered by oral intragastric intubation to 1 group of 5 fasted males and 1 group of 5 fasted female rats at a dosage of 5,000mg/kg. No deaths occurred during the study, therefore the oral lethal dose 50 was greater than 5000 mg/kg. No clinical signs of toxicity were observed in 4 female rats or 3 of the male rats. Lung nose was observed in 1 male rat on test day 2 only. Another male rat began exhibiting clinical signs on test day 13 until study completion. The signs observed included lethargy, bloated perineum, lung noise, red stained face and paws, and ruffed fur. One female rat exhibited red-stained head on test day 3 only.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
At 5,000mg/kg there was 0% mortality for males and females.
Clinical signs:
other: Again no clinical signs of toxicity were observed in 4 female rats or 3 of the male rats. Lung noise was observed in 1 male rat on test day 2 only. Another male rat began exhibiting clinical signs on test day 13 until study completion. The signs observ
Gross pathology:
The gross observations for the male and female study rats were non-specific and not indicative of target organ toxicity. The small and large intestines were distended with gas in one male and one female rat at the 5,000mg/kg dose.
Other findings:
No additional data

Any other information on results incl. tables

No additional data

Applicant's summary and conclusion

Interpretation of results:
relatively harmless
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions of this study, male and female rats' lethal dose 50 was greater than 5,000mg/kg. This test substance is considered to be very low in toxicity when administered orally to fasted male and female rats.
Executive summary:

In an acute toxicity study a single oral dose of Corfree® M1 (CAS# 72162-23-3) was administered in a acetone and water based solution to 5 male and 5 female groups of CrlCD (SD) IGS BR rats at dose level of 5,000 mg/kg, after a fasted period of 20.5 hours. This study was based on OECD Guidelines for the Testing of Chemicals Section 4: Health Effects, No. 401 (1987). Animals were observed, mortality noted and weighed daily. No clinical signs of toxicity were observed in 4 female rats or 3 of the male rats. Lung noise was observed in 1 male rat on test day 2 only. Another male rat began exhibiting clinical signs on test day 13 until study completion. The signs observed included lethargy, bloated perineum, lung noise, red stained face and paws, and ruffed fur. One female rat exhibited red-stained head on test day 3 only. When survivors were sacrified, no significant abnormality was detected at 5,000 mg/kg level. Under the test conditions of this study, the male and female rats were equally as sensitive. Therefore, based on the oral lethal dose 50 (LD50) of male and female rats considering as the worst case, Corfree® M1was considered as not classifiable based on EEC Directive 93/21.