Registration Dossier

Administrative data

Description of key information

Oral (OECD 423), rat: 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:
20 Sep - 7 Oct 2004
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)
Version / remarks:
adopted in Feb 2002
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
2004/73/EC
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Behörde für Arbeit, Gesundheit und Soziales, Hamburg, Germany
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at start of adaptation: 40 days (males), 47 days (females)
- Weight at study initiation: 192 - 206 g (males), 171 - 190 g (females)
- Fasting period before study: animals were fasted 16 h prior to administration
- Housing: groups of 3 animals in MAKROLON cages (type III), granulated textured wood was used as bedding material
- Diet: ssniff R/M-H V1534 (ssniff Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum, analysis was performed
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40 - 70
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.17 mL/kg bw
Doses:
2000 mg/kg bw (step 1 and 2)
No. of animals per sex per dose:
3 males (step 1) and 3 females (step 2)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed before and immediately 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Observations on mortality were made at least once daily.
Individual body weights were determined before administration of the test substance and thereafter in weekly intervals. Changes in weight was calculated when survival exceeded one day.
- Necropsy of survivors performed: yes
- Other examinations performed: From animals which survive 24 h or longer a microscopic examination of all organs which showed evident lesions was performed, if necessary.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 cut-off of 5000 mg/kg bw according to OECD 423
Mortality:
No mortality occurred during the study period.
Clinical signs:
No signs of toxicity were observed up to the end of the 14-day observation period.
Body weight:
All animals gained the expected body weight at the end of the study.
Gross pathology:
No pathological findings were noted at necropsy.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study in rats a LD50 > 2000 mg/kg bw was found.
Executive summary:

Under the present test conditions a single oral administration of 2000 mg Mintonat/kgb.w. rats did not reveal any signs of toxicity. Mortality did not occur, all male and female animals gained the expected body weight at the end of the study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

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Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral

The acute oral toxicity of the test substance was assessed in a limit test according to OECD Guideline 423 and in compliance with GLP (2004). A total dose of 2000 mg/kg bw of the test substance was administered to 3 male (step 1) and 3 female rats (step 2). Animals were observed for clinical signs immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All surviving animals were observed for 14 days. Furthermore, individual body weights were determined before administration and thereafter in weekly intervals. Macroscopic examination was performed on test Day 15 (14 days after administration) at terminal sacrifice. There were no mortalities during the observation period and body weight gain of all animals was considered to be normal. Macroscopic post mortem examination did not reveal any abnormalities. Based on the results of this study, the LD50 value was determined to be > 2000 mg/kg bw in rats. In accordance with OECD Guideline 423, a cut-off value of 5000 mg/kg bw was derived, since no mortality occurred at 2000 mg/kg bw.

Inhalation

In accordance with Regulation (EC) No 1907/2006, Annex VIII, Point 8.5.2, Column II, there is no study required since exposure of humans via inhalation is unlikely.

Dermal

According to Regulation (EC) No 1907/2006, Annex VIII, Point 8.5.3, Column II an acute dermal toxicity study does not need to be conducted, if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation) or, in the absence of an in vivo study by the oral route, no systemic effects after dermal exposure are predicted on the basis of non-testing approaches (e.g. read-across, QSAR studies).

In an acute oral toxicity study in rats performed according to OECD Guideline 423 (2004), the test substance did not reveal any signs of toxicity and no mortality occurred at the limit dose of 2000 mg/kg bw. In a skin irritation study in rabbits according to OECD Guideline 404 no systemic intolerance reactions were observed (2004). Moreover, no changes in behaviour were noted in a guinea pig maximization test according to OECD Guideline 406 (2004).

In conclusion, the test substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (skin irritation and skin sensitisation) and therefore, no acute dermal toxicity study needs to be conducted.

Justification for classification or non-classification

The available data on acute oral toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) No 1272/2008, and are therefore conclusive but not sufficient for classification.