Registration Dossier

Administrative data

Description of key information

oral LD50 (rat) = 962 mg/kg bw  (technical product)
dermal LD50 (rat) > 2000 mg/kg bw (technical product)
inhalation LC50: waived (exposure considerations)

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:
21 June 2006 - 18 July 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
yes
Remarks:
Storage of the vehicle at room temperature instead of refrigerator. No effect presumed on outcome of the study.
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Young healthy adult rats, 8-12 weeks old, body weight at start: 172-194 g, acclimatisation period: 13-15 days.
Husbandry: group caging (4 animals per cage), 12 h light / 12 hours dark; 19-25°C, 30-70% relative humidity.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
single dose
Doses:
Sighting study 1: 2000 mg/kg bw (single female rat)
Sighting study 2: 300 mg/kg bw (single female rat)
Main study: 300 mg/kg bw (four female rats)
No. of animals per sex per dose:
Sighting study 1: 1 female rat, one dose
Sighting study 2: 1 female rat, one dose
Main study: 4 female rats, one dose
Control animals:
no
Statistics:
not necessary
Preliminary study:
Sighting study 1 with one female rat, dosage 2000 mg/kg bw: animal found dead after 1 day.
Sighting study 2 with one female rat, dosage 300 mg/kg bw: no evident toxicity and no moratlity.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Sighting study 1: 1/1
Sighting study 2: 0/1
Main study: 0/4
Clinical signs:
Sighting study 1: decreased activity, tremor, incoordination, hunched back, decreased righting reflex, narrow eye aperture, paleness, piloerection, dyspnoea. lachrymation. First symptoms appeared 2 h after treatment.
Sighting study 2, main study: no visible symptoms.
Body weight:
Sighting study 1: not less than at starting.
Sighting study and main study: weight development was undisturbed.
Gross pathology:
No macroscopic changes in all animals.
Sighting study 1: Reddish mottled lungs as indication of an acute circulatory insufficiency during death of the animal.
Sighting study 2 and main study: Pinprick-sized haemorrhages in the lungs (sighting study: 1/1, main study: 2/4)m, hydrometra in the uterus (main study: 2/4).
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
2000 mg/kg bw of the test item caused mortality in female Wistar rat (1/1) after single oral administration.
300 mg/kg of the test item caused no adverse effect and no mortality in female Wistar rat (0/5) after single oral administration.
The test item was ranked into GHS class 4 and into EPA category III ("Caution") and is considered harmful if swallowed according to EU Commission Directive 2001/59/EC (R22).
Executive summary:

An acute oral toxicity test (fixed dose method) according to OECD 420 was performed on the test item.

At 2000 mg/kg bw, one female rat was dead within 1 day after one single oral adiminstration. At 300 mg/kg bw, all five female rats tested survived the whole observation period of 14 days. The acute oral toxicity of the test item against female Wistar rats was estabhlished between 300 and 2000 mg/kg bw.

The test item was rankec into the GHS class 4 and into the EPA Category III ("Caution").

The test item was considered harmful if swallowed (R22) according to EU Commission Directive 2001/59/EC.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
500 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:
04 July 2006 - 18 July 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 1987
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Young healthy adult rats, age not reported, 13 days of acclimatisation; weight range: male 249-258 g, female 201-220 g; husbandry: individual caging at 12 h light and 12 h dark, 19-25°C, 30-70% relative humidity.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
A limit test was carried out involving a dose of 2000 mg/kg bw with five malev and female animals each.
A single dermal dermal administration followed by a 14-d observation period was performed.
One day before the start of the test the trunk of the animals was shaved. The test item was applied in pure form in a single dose on about 10% of the total body surface for 24 h. Sterile gauze pads were placed on the skin of the rats and kept in contact with the skin by hypoallergenic plaster. Then the entire trunk of the animal was wrapped with semiocclusive plastic wrap for 24 hours. At the end of the exposure period, resuidual test item was removed by using water with body temperature.
Duration of exposure:
24 hours single exposure
Doses:
On single dosis: 2000 mg/kg bw
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
no
Details on study design:
Clinical observations were done for 14 days: 1 h and 5 h after the end of exposure and once a day on the following days.
Individual observations were done on the skin, fur, eyes, mucous membranes, respiration, circulation, autonomic and central nervous system, somatomotoric activity and behaviour.
Body weight was determined at the start (day 0) and on days 7 and 14.
Gross necropsy was performed on all animals after 14 days. External appearance and abnormalities of the organs in the cranial, thoracic and abdominal cavities were recorded.
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed in this test.
Clinical signs:
No dermal changes in male rats.
Female rats: erythema (5/5), epithelisation (5/5), necrosis (1/5). After 9-11 days, the skin in 4 of 5 animals returned to normal.
Body weight:
The mean body weight and the body weight gain were in the normal range during the observation period.
Gross pathology:
Pinprick-sized haemorrhages in the lungs (male 3/5, female 3/5) were observed.
One female had scar on the site of administration due to test item.
Other findings:
Behaviour and general state of male and female animals were normal during the whole observation period.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
AFLAMMIT SAP does not fulfill the criteria for classification and labelling according to the Commission Directive 2001/59/EC.
AFLAMMIT SAP was ranked into the WHO toxic class II-III (moderately/slightly hazardous).
AFLAMMIT SAP was ranked into the EPA toxci class III ("Caution").
Because of the skin effects (one animal showed necrosis and scar at the end of the recovery period) classification with "corrosive, R34" is considered to be necessary.
Executive summary:

A acute dermal toxity test was performed on the test item AFLAMMIT SAP using Wistar rats.The test item was applied in one dose (2000 mg/kg bw) for 24 hours followed by a 14 day observation period.

No mortalities occured in male and female rats (five male and five female): LD50 > 2000 mg/kg bw.

Symptoms in the skin were observed only in female rats and were reversible after 11 day with the exeption of one female rat, which showed necrosis and scar on the treated skin at necropsy.

Pinprick-size haemorrhages were observed in 3 of male and 3 of 5 female rats by necropsy after 14 days.

AFLAMMIT SAP does not fulfill the criteria for classification adn labelling according to the Commission Directive 2001/59/EC.

AFLAMMIT SAP was ranked into the classes WHO II-III (moderately/slightly hazardous) and EPA III ("Caution").

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Acute oral LD50 = 300 -2000 mg/kg bw AFLAMMIT SAP. Evidence from similar technical product: oral LD50=962 mg/kg bw (Tuffnell 1994).

Acute dermal LD50 > 2000 mg/kg bw AFLAMMIT SAP. Evidence from similar technical product: dermal LD50>2000 mg/kg bw (Tuffnell 1991).


Justification for selection of acute toxicity – oral endpoint
OECD 423 with applicants product: LD50 = 300-2000 mg/kg bw/day

Justification for selection of acute toxicity – inhalation endpoint
Test waived (exposure considerations).

Justification for selection of acute toxicity – dermal endpoint
corrosive to rat skin

Justification for classification or non-classification

oral LD50 (rat) = 962 mg/kg bw (technical product: 68% in water); substance is considered harmful if swallowed (Xn R22, GHS cat 4)

dermal LD 50 (rat) > 2000 mg/kg bw (technical product: 65-68% in water); substance is not hazardous (GHS cat 5)

inhalation LC50: waived (exposure considerations).