Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989-01-26 to 1989-02-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1984
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
A mixture of isomers of: 1,1'-[(3,5(or 2,4 or 4,6 or 2,6)-dihydroxy-o(or m or p)-phenylene)bis(azo-meta-phenyleneazo{1-[3-(dimethylamino)propyl]-1,2-dihydro-6-hydroxy-4-methyl-2-oxopyridine-5,3-diyl})]dipyridinium-dichloride-dihydrochloride; 1-(1-[3-(dimethylamino)propyl]-5-{3-[x-(4-{1-[3-(dimethylamino)propyl]-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-5-pyridinio-3-pyridylazo}phenylazo)-2,4(or 2,6 or 3,5 or 4,6)-dihydroxyphenylazo]phenylazo}-1,2-dihydro-6-hydroxy-4-methyl-2-oxo-3-pyridyl)pyridinium-dichloride-dihydrochloride (where x is variable)
EC Number:
404-540-1
EC Name:
A mixture of isomers of: 1,1'-[(3,5(or 2,4 or 4,6 or 2,6)-dihydroxy-o(or m or p)-phenylene)bis(azo-meta-phenyleneazo{1-[3-(dimethylamino)propyl]-1,2-dihydro-6-hydroxy-4-methyl-2-oxopyridine-5,3-diyl})]dipyridinium-dichloride-dihydrochloride; 1-(1-[3-(dimethylamino)propyl]-5-{3-[x-(4-{1-[3-(dimethylamino)propyl]-1,6-dihydro-2-hydroxy-4-methyl-6-oxo-5-pyridinio-3-pyridylazo}phenylazo)-2,4(or 2,6 or 3,5 or 4,6)-dihydroxyphenylazo]phenylazo}-1,2-dihydro-6-hydroxy-4-methyl-2-oxo-3-pyridyl)pyridinium-dichloride-dihydrochloride (where x is variable)
Cas Number:
159405-95-5
Molecular formula:
C50H56Cl4N14O6
IUPAC Name:
1'-[3-(dimethylamino)propyl]-5'-(2-{3-[2-(4-{2-[3-(2-{1'-[3-(dimethylamino)propyl]-6'-hydroxy-4'-methyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium-5'-yl}diazen-1-yl)phenyl]diazen-1-yl}-2,6-dihydroxyphenyl)diazen-1-yl]phenyl}diazen-1-yl)-6'-hydroxy-4'-methyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium 1'-[3-(dimethylamino)propyl]-5'-(2-{4-[2-(4-{2-[4-(2-{1'-[3-(dimethylamino)propyl]-6'-hydroxy-4'-methyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium-5'-yl}diazen-1-yl)phenyl]diazen-1-yl}-2,6-dihydroxyphenyl)diazen-1-yl]phenyl}diazen-1-yl)-6'-hydroxy-4'-methyl-2'-oxo-1',2'-dihydro-1λ⁵-[1,3'-bipyridin]-1-ylium tetrahydrochloride tetrachloride
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga, Sulzfeld, West-Germany
- Age at study initiation: approx. 7 weeks
- Weight at study initiation: males: 272 - 316 g, females: 180 - 205 g
- Fasting period before study: no
- Housing: housed in groups of five per sex in polycarbonate cages containing purified sawdust as bedding material
- Diet (e.g. ad libitum): free access to standard pelleted laboratory animal diet
- Water (e.g. ad libitum): free access to tap-water.
- Acclimation period: 7 days under laboratory conditions.

ENVIRONMENTAL CONDITIONS
- Temperature: 21 ± 3 °C
- Humidity: 30 - 70 %
- Air changes (per hr): 7.5 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: back of the animal
- % coverage: approximately 25 cm2 (5×5 cm) for males and 18 cm2 (3.5×5 cm) for females
- Type of wrap if used: gauze patch fixed successively to aluminium foil and flexible bandage with drops of petrolatum

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test article was removed with tissue moistened with tap-water.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg bw
- Concentration (if solution): 200 mg/ml
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 10 ml/kg bw
- Concentration (if solution): 200 mg test item/ml vehicle
- Purity: reverse osmosis
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males, 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: test days 1 (pre-administration), 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
At periodic intervals on the day of dosing (day 1) and once daily thereafter. All signs of reaction to treatment were recorded with particular attention paid to changes in the skin, fur, eyes and mucous membranes, as well as to behaviour pattern, tremors, convulsion, salivations, diarrhoea, lethargy, sleep and coma. Changes of the treated skin were described immediately after bandage removal (day 2) and on days 5, 8 and 15. Furthermore the body weight / body weight gain was recorded.
Statistics:
no statistics applied

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; number of animals: 5; number of deaths: 0
Female: 2000 mg/kg bw; number of animals: 5; number of deaths: 0
Clinical signs:
other: No deaths or signs of systemic toxicity were observed. Signs of toxicity (local): all males and 4/5 females had a brown mottled appearance of the treated skin for the duration of the study. 4/5 females also had red spots on the treated skin on day 15.
Gross pathology:
No substance-related macroscopic findings were observed.

Applicant's summary and conclusion

Interpretation of results:
other: not classified within the CLP Regulation (EC 1272/2008)
Conclusions:
The dermal LD50 value of test substance in rats of both sexes was estimated to exceed 2000 mg/kg body weight.
Executive summary:

The study followed the protocol as given in OECD guideline 402.

The substance was administered to rats of both sexes by dermal application at 2000 mg/kg body weight for 24 hours, followed by a 15 day observation period. No mortality occurred during the study period. The dermal LD50 value of the substance in rats of both sexes was estimated to exceed 2000 mg/kg body weight.

The substance is not classified for acute dermal toxicity within the CLP Regulation (EC 1272/2008).