Registration Dossier

Administrative data

Description of key information

          

Due to the physical-chemical properties of amine synergist (i.e. low vapour pressure), inhalationexposure is not expected to occur under normal and foreseeable handling and use conditions.

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:
25 August 1999 - 25 February 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Age at study initiation: Young adult animals- Weight at study initiation: animals of comparable weight (150g - 300g) (+/- 20% of the mean weight)- Housing: stainless steel wire mesh cages, type DK-III (single housing)- Diet (e.g. ad libitum): ad libitum (feed assayed for chemical and microbiological contaminants)- Water (e.g. ad libitum): Tap water ad libitum per day- Acclimation period: acclimatization for at least 1 weekENVIRONMENTAL CONDITIONS- Temperature (°C): The animals were housed in fully air-contitioned rooms. Central air-conditioning guaranteed a range of 20 - 24 degrees centigrade for temperature and of 30 - 70 % for relative humidity. There were no deviations from these ranges, which influenced the results of the study.- Photoperiod (hrs dark / hrs light): 12 h/12 h
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE- Concentration in vehicle: 40.00 g/100mL- Amount of vehicle (if gavage): 5.00 ml/kg- Justification for choice of vehicle: The test substance could not be homogeneously distributed in aqua bidest.
Doses:
2,000 mg/kg bw
No. of animals per sex per dose:
3 males / 3 females
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days - Examinations performed: clinical signs and symptoms, body weight,mortality, pathology: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality.
Clinical signs:
Signs of toxicity noted in female animals comprised impaired general state, dyspnoea and staggering. These syptoms were considered to be unspecific toxicity symptoms. The animals appeared normal 2 days after application.The male rats did not show any symptoms.
Body weight:
The excepted body weigth gain was observed in the course of the study.
Gross pathology:
No abnormalities were noted at necropsy of animals sacrificed at the end of the study.
Conclusions:
Under the test conditions, the LD50 value of the test substance was > 2,000 mg/kg bw.
Executive summary:

A study was conducted to determine the acute oral LD50 of the test substance according to EPA OPPTS 870.1100, OECD Guideline 423 and EU Method B.1.

No mortality was observed at the dose level of 2,000 mg/kg bw .

Under the conditions of the study, the LD50 of the test substance was therefore >2,000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 March 2010 - 13 April 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.- Age at study initiation: Young adult animals (approx. 10 weeks old)- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.- Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Woody-Clean type 3/4, Tecnilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Enviro-dri, Tecnilab-BMI BV, Someren, The Netherlands). - Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).- Water (e.g. ad libitum): Free access to tap water.- Acclimation period: The acclimatization period was at least 5 days before the start of treatment under laboratory conditions.- Health inspection: A health inspection was performed prior to treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.ENVIRONMENTAL CONDITIONS- Temperature (°C): 20.0– 21.7ºC- Humidity (%): 41 - 54%- Air changes (per hr): approximately 15 air changes per hour- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day. IN-LIFE DATES: From: 30 March 2010 to 13 April 2010
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.The test substance was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only. * Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).Frequency: Single dosage, on Day 1.Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw (2.02 mL/kg bw) .Dose volume calculated as dose level (g/kg) / specific gravity.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Dose level (volume): 2000 mg/kg bw (2.02 mL/kg bw). Dose volume calculated as dose level (g/kg) / specific gravity.DOSAGE PREPARATION: The test substance was dosed undiluted as delivered by the sponsor.Duration of observation period following administration: 14 days- Frequency of observations and weighing:Mortality/Viability: Twice dailyBody weights: Days 1 (pre-administration), 8 and 15.Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.- Necropsy of survivors performed: yes- Other examinations performed: none.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Lethargy, tremor, hunched posture, laboured and shallow respiration, piloerection, chromodacryorrhoea, ptosis, and hyperthermia were noted in the majority of animals. Most animals had recovered from the symptoms between Days 4 and 6. General or focal erythema, scabs, scars, scales, fissures, dryness, thickened area, hypersensitivity to touch and necrosis were seen in the treated skin-area of most of the animals during the observation period.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Conclusions:
Under the test conditions, the dermal LD50 of the test substance in Wistar rats was > 2000 mg/kg bw.
Executive summary:

A study was conducted to determine the LD50 of the test substance according to OECD Guideline 402, EC Method B.3, EPA OPPTS 870.1200 and JMAFF Notification No. 8147 .

No mortality was observed at the dose level of 2,000 mg/kg bw in rats after a single dermal application.

Under the test conditions, the dermal LD50 of the test substance in Wistar rats was > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Based on two acute oral toxicity OECD guidelines studies, single dose levels of 2,000 and 5,000 mg/kg/ bw of amine synergist administered in rats resulted in no mortality. The oral LD50 was found to be > 5,000 mg/kg bw in Crl:CD(SD) BR rats (Gardner, 1987) and > 2,000 mg/kg bw in Wistar rats (Wiemann, 2000). Both studies suggest that the substance has a low acute toxicity when administered via the oral route.

A single application of 2,000 mg/kg bw of amine synergist applied to the skin of rats resulted in no mortality. The LD50 was determined to be > 2,000 mg/kg bw, indicating a low acute dermal toxicity (Beerens-Heijnen, 2010).

Due to the physical-chemical properties of amine synergist (i.e. low vapour pressure), inhalation exposure is not expected to occur under normal and foreseeable handling and use conditions.

Justification for classification or non-classification

The available data for amine synergist indicates a low potential for acute oral and dermal toxicity. The substance therefore does not meet the requirement for classification according to CLP (EC 1272/2008) criteria.