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Description of key information

For the acute oral toxicity study with the test item Aldehyde M in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 > 2000 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:
2013-03-05 to 2013-03-21
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-study according to OECD/EU guideline. This study is considered as scientific acceptable.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 December 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
30 May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90.
- Age of animals: Young adult rats, 8 weeks old in group 1 and 2
- Weight at study initiation: 193-208 g
- Fasting period before study: the day before treatment
- Housing: 3 animals/sex/cage
- Diet: ssniff® SM R/M-Z+H complete diet, ad libitum
- Water: tap water from watering bottles ad libitum
- Acclimation period: 5 days in first step and 6 days in second step

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 10-15 air exchanges/hour by central air-condition system
- Photoperiod (hrs dark / hrs light): 12/12, artificial light, from 6 am. to 6 pm.

IN-LIFE DATES: From: 2013-03-05 To: 2013-03-21
Route of administration:
oral: gavage
Vehicle:
other: Helianthi annui oleum raffinatum
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 10 mL/kg bw
- Justification for choice of vehicle: common vehicle
- Lot/batch no.: 19T3

DOSAGE PREPARATION: Formulations were prepared just before the administration and stirred continuously during the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose: No severe acute toxicity was expected.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
2x 3 female animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h, after the treatment and once per day for 14 days thereafter
- Frequency of weighing: on day 0 (shortly before the treatment), on day 7 and on day 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
not applicable
Preliminary study:
not applicable
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
The test item Aldehyde M did not induce mortality following a single oral administration to female rats at a dose of 2000 mg/kg bw. All female rats survived the performed treatment until the end of the 14-day observation period.
Clinical signs:
In group 1 treated with 2000 mg/kg bw of the test item clinical sign of reaction comprised of decreased activity (3 cases of 57 observations). This symptom (score -1) was observed in all animals. It was detected on the treatment day 30 min. after the treatment.
In group 2 treated with 2000 mg/kg bw of the test item clinical sign of reaction comprised of decreased activity (2 cases of 57 observations). This symptom (score -1) was observed in one animal. It was detected on the treatment day between 30 min. and 1 hour after the treatment. The other two animals were free of symptoms throughout the observation period.
Body weight:
The mean body weight of the other animals corresponded to their species and age throughout the study.
Gross pathology:
All animals treated with 2000 mg/kg bw of test item survived until the scheduled necropsy on Day 15.
Slight hydrometra was observed in two females of the group 1 and moderate hydrometra was found in one female of the group 2. Hydrometra is physiological finding and connected to the cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.
Other findings:
not applicable

Summary of lethality

 

Groups

Treatment

Lethality

Test item

Dose (mg/kg bw)

Females

1

Aldehyde M Step 1

2000

0/3

2

Aldehyde M Step 2

2000

0/3

 

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 was determined to be above 2000 mg/kg bw. According to the current EU Regulation on classification, labelling and packaging (CLP) (EC) No 1272/2008 no classification is required for the test item Aldehyde M.
Executive summary:
In this acute oral toxicity study, two groups of female rats (Crl(WI)Br) were given a single oral dose of the test item Aldehyde M at a concentration of 2000 mg/kg bw. The starting dose was selected on the basis of the available information about the test item.

The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level. Therefore, treatment with 2000 mg/kg bw was repeated on further three female rats. Again, no animal died in the second step, thus no further testing was required. The stopping criteria of Annex 2d of OECD Guideline No. 423 were met.

Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the 15th day after the treatment.

No lethality was noted following oral administration of a single dose of 2000 mg/kg bw. In the first step, CNS - and emotion symptom as decreased activity was observed in all animals on the treatment day 30 min after the treatment. In the second step, CNS - and emotion symptom as decreased activity was observed in one animal on the treatment day between 30 min and 1 hour after the treatment. In the other two animals, no clinical symptoms were observed on the day of the treatment and during the 14-day observation period. The body weight development was normal in all animals.

Altogether 6 animals were subjected to scheduled sacrifice during the study. All organs of the animals treated with 2000 mg/kg bw dose proved to be free of treatment related gross pathological changes. The method used is not intended to allow for the calculation of a precise LD50 value. However, for this acute oral toxicity study with the test item Aldehyde M in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 ≥ 2000 mg/kg bw).

The test item is ranked into classes of the current EU Regulation on classification, labelling and packaging (CLP) (EC) No 1272/2008. According to the current Regulation (EC) No 1272/2008 no classification is required for the test item Aldehyde M.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
2 000 mg/kg bw
Quality of whole database:
GLP study according to OECD/EU guideline. Reliable without restrictions.

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

In the acute oral toxicity study, two groups of female rats (Crl(WI)Br) were given a single oral dose of the test item Aldehyde M at a concentration of 2000 mg/kg bw. The starting dose was selected on the basis of the available information about the test item.

The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level. Therefore, treatment with 2000 mg/kg bw was repeated on further three female rats. Again, no animal died in the second step, thus no further testing was required. The stopping criteria of Annex 2d of OECD Guideline No. 423 were met.

Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on the 15th day after the treatment. No lethality was noted following oral administration of a single dose of 2000 mg/kg bw. In the first step, CNS - and emotion symptom as decreased activity was observed in all animals on the treatment day 30 min after the treatment. In the second step, CNS - and emotion symptom as decreased activity was observed in one animal on the treatment day between 30 min and 1 hour after the treatment. In the other two animals, no clinical symptoms were observed on the day of the treatment and during the 14-day observation period. The body weight development was normal in all animals. Altogether 6 animals were subjected to scheduled sacrifice during the study. All organs of the animals treated with 2000 mg/kg bw dose proved to be free of treatment related gross pathological changes.

The method used is not intended to allow for the calculation of a precise LD50 value. However, for this acute oral toxicity study with the test item Aldehyde M in rats the determined LD50 is greater than 2000 mg/kg bw (LD50 ≥ 2000 mg/kg bw). The test item is ranked into classes of the current EU Regulation on classification, labelling and packaging (CLP) (EC) No 1272/2008. According to the current Regulation (EC) No 1272/2008 no classification is required for the test item Aldehyde M.

 


Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for classification or non-classification

According to Regulation (EC) No 1272/2008 (CLP) and Directive 67/548/EEC no classification for acute oral toxicity is required for the test item.