5-((4-chloro-6-((8-hydroxy-3,6-disulfo-7-((2-sulfo-4-((2(sulfooxy)ethyl)sulfonyl)phenyl)diazenyl)naphthalen-1-yl)amino)-1,3,5-triazin-2-yl)amino)-4-hydroxy-3-((Z)-(3-sulfophenyl)diazenyl)naphthalene-2,7-disulfonic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

Data is from experimental report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1978

Report date:

1978

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

To determine the acute median lethal dosage after oral administration to rats.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]]bisnaphthalene-1,5-disulphonate

Cas Number:

68110-30-5

Molecular formula:

C58H30Cl2N14Na8O26S8

IUPAC Name:

octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]]bisnaphthalene-1,5-disulphonate

Test material form:

solid: particulate/powder

Details on test material:

IUPAC Name: octasodium 2,2'-[(2,2'-disulphonato[1,1'-biphenyl]-4,4'-diyl)bis[imino(6-chloro-1,3,5-triazine-4,2-diyl)imino(1-hydroxy-3-sulphonatonaphthalene-6,2-diyl)azo]]bisnaphthalene -1,5-disulphonate
Name reported in publication: Procion Orange H-ER
InChI:1S/C58H38Cl2N14O26S8.8Na/c59-53-65-55(61-27-7-11-31-25(19-27)21-45(105(89,90)91)47(49(31)75)73-71-39-17-15-35-37(51(39)107(95,96)97)3-1-5-41(35)101(77,78)79)69-57(67-53)63-29-9-13-33(43(23-29)103(83,84)85)34-14-10-30(24-44(34)104(86,87)88)64-58-68-54(60)66-56(70-58)62-28-8-12-32-26(20-28)22-46(106(92,93)94)48(50(32)76)74-72-40-18-16-36-38(52(40)108(98,99)100)4-2-6-42(36)102(80,81)82;;;;;;;;/h1-24,75-76H,(H,77,78,79)(H,80,81,82)(H,83,84,85)(H,86,87,88)(H,89,90,91)(H,92,93,94)(H,95,96,97)(H,98,99,100)(H2,61,63,65,67,69)(H2,62,64,66,68,70);;;;;;;;/q;8*+1/p-8/b73-71+,74-72+;;;;;;;;
Smiles:[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].c1(c(cc(cc1)Nc1nc(nc(n1)Cl)Nc1cc2cc(c(c(c2cc1)O)\N=N\c1c(c2cccc(c2cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])c1c(cc(cc1)Nc1nc(nc(n1)Cl)Nc1cc2cc(c(c(c2cc1)O)\N=N\c1c(c2cccc(c2cc1)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)[O-]
Molecular Weight: 1850.3 g/mole
Molecular Formula: C58H38Cl2N14O26S8.8Na

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River U.K. Limited, Margate, Kent,
- Weight at study initiation: weight-range of 137 - 159 g for males; and 126 - 143 g for females.
- Fasting period before study: Rats were deprived of food for 16 hours before dosing.
- Housing:Animals were housed throughout in suspended polypropylene cages with grid mesh floors.
- Diet (e.g. ad libitum): pelleted rodent diet, ad libitum
- Water (e.g. ad libitum):tap water, ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 degree ± 2 degree C
- Photoperiod (hrs dark / hrs light): 12-hour lighting cycle during a minimum period of seven days.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: aqueous solution

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% w/v
- Amount of vehicle (if gavage):10 ml/kg

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

groups of 5 male and 5 female rats

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:The animals were closely observed throughout the first hour for signs of reaction to the administered material, followed by examination at regular intervals for the remainder of the day. Subsequently, until termination, they were examined at least daily. The time-course of reaction to treatment and subsequent recovery was assessed subjectively by visual appraisal of the animals and, more objectively, by examination of the bodyweight changes 7 and 14 days after dosing.
- Necropsy of survivors performed: yes, all animals that died were subjected to thorough necropsy with the objective of locating target tissues damaged by the test material. Animals which survived to Day 15 were killed and similarly examined to assess any residual or delayed pathology.
- Other examinations performed: Signs of reaction and mortalities were recorded during a 14-day observation period.

Statistics:

not specified

Results and discussion

Preliminary study:

Two rats of each sex were employed in preliminary range finding studies at the maximum required dosage of 5000 mg/kg.No signs of reaction to treatment were observed during a preliminary study. Bright orange coloured faeces were present on Days 2 and 4. Necropsy on Day 15 revealed no abnormalities,except for orange-colouration of the kidneys.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality was observed

Mortality:

No mortality was observed at 5000 mg/kg bw.

Clinical signs:

other: The overt signs of reaction to treatment comprised piloerection at 1-2.5 hours after treatment and a decrease in motor activity over the period 0.5 - 6 hours, in all animals. The presence of bright-red pigmented faeces from the day of dosing to Day 3 prob

Gross pathology:

Terminal necropsy on Day 15 revealed no significant lesions that could be attributable to treatment; however, the renal cortices were stained slight orange, showing some deposition of material.

Other findings:

Under the conditions of this study, test chemical was absorbed sufficiently to produce, in all animals, minor signs of reaction to treatment. Staining of the renal cortices afforded evidence of urinary excretion.

Any other information on results incl. tables

Table – Distribution of signs and mortality among groups of male and female rats given a single, maximum practicable, oral dosage of 5000 mg/kg, H-ER as a 50% w/v aqueous solution

Dosage Mg/kg

Observations

Animal number and sex

Number showing effect at time after dosing

♂

Hour

Day

1

2

3

4

5

6

7

8

9

10

⅟2

⅟2

1

2⅟2

4

6

2

3

4

5

6

7

8

9

10

11

12

13

14

15

am

pm

5000

Body weight: (g)

Initial

159

138

152

137

152

143

137

139

140

153

Day 8

248

213

222

216

233

230

214

214

210

224

Day 15

306

253

276

270

280

278

266

264

258

274

Increment

147

115

124

133

128

135

129

125

118

121

Mortality:

^0/10

Signs of reaction:

Piloerection

+

+

+

+

+

+

+

+

+

+

^9/10

^10/10

Hypoactivity

+

+

+

+

+

+

+

+

+

+

^10/10

^10/10

^10/10

^10/10

^10/10

^6/10

Inactivity

+

+

+

+

^4/10

Faeces, pigmented bright red

+

+

+

+

+

+

+

+

+

+

^9/10

^10/10

^10/10

^10/10

^10/10

Necropsy

NSL

+

+

+

+

+

+

+

+

+

+

^10/10

Renal cortex, stained slight orange

+

+

+

+

+

+

+

+

+

+

^10/10

♀

5000

Body weight: (g)

Initial

137

138

136

132

141

126

137

143

128

142

Day 8

175

174

169

180

189

162

179

180

164

186

Day 15

190

186

189

196

220

178

197

197

182

217

Increment

53

48

53

64

89

52

60

54

54

75

Mortality:

^0/10

Signs of reaction:

Piloerection

+

+

+

+

+

+

+

+

+

+

^10/10

^10/10

Hypoactivity

+

+

+

+

+

+

+

+

+

+

^10/10

^10/10

^10/10

^10/10

^10/10

^10/10

Faeces, pigmented bright red

+

+

+

+

+

+

+

+

+

+

^9/10

^10/10

^10/10

^10/10

^10/10

Necropsy

NSL

+

+

+

+

+

+

+

+

+

+

^10/10

Renal cortex, stained slight orange

+

+

+

+

+

+

+

+

+

+

^10/10

 

+ identifies animal showing response

NSL No significant lesions

Applicant's summary and conclusion

Interpretation of results:

other: Not classified

Conclusions:

The acute oral toxicity dose (LD50) was considered to be >5000 mg/kg bw, when groups of 5 male and 5 female Wistar rats were treated with the given test chemical via oral gavage route.

Executive summary:

The acute oral toxicity study was conducted in wistar rats by using test chemical at the dose concentration of 5000 mg/kg bw. The given test chemical (Procion Orange H-ER, ORG/98, Code B6100 Z0593, a powder) was prepared for administration as a 50% w/v aqueous solution but dosages were expressed gravimetrjcally. Dosages were determined according to the fasted body weight of the animals, which were dosed orally at approximately 11.00 hours with a dosage volume of 10 ml/kg. In preliminary range finding studies, 2 rats of each sex were employed at the maximum required dosage of 5000 mg/kg. No signs of reaction to treatment were observed during a preliminary study. Bright orange coloured faeces were present on Days 2 and 4. Necropsy on Day 15 revealed no abnormalities, except for orange-colouration of the kidneys. In main study, the animals were closely observed throughout the first hour for signs of reaction to the administered material, followed by examination at regular intervals for the remainder of the day. Subsequently, until termination, they were examined at least daily. The time-course of reaction to treatment and subsequent recovery was assessed subjectively by visual appraisal of the animals and, more objectively, by examination of the bodyweight changes 7 and 14 days after dosing. All animals that died were subjected to thorough necropsy with the objective of locating target tissues damaged by the test material. Animals which survived to Day 15 were killed and similarly examined to assess any residual or delayed pathology. Signs of reaction and mortalities were recorded during a 14-day observation period. No mortality was observed at 5000 mg/kg bw. The overt signs of reaction to treatment comprised piloerection at 1-2.5 hours after treatment and a decrease in motor activity over the period 0.5 - 6 hours, in all animals. The presence of bright-red pigmented faeces from the day of dosing to Day 3 probably indicated poor absorption of the dose. Animals gained weight normally over the period of observation. Terminal necropsy on Day 15 revealed no significant lesions that could be attributable to treatment; however, the renal cortices were stained slight orange, showing some deposition of material. Under the conditions of this study, test chemical was absorbed sufficiently to produce, in all animals, minor signs of reaction to treatment. Staining of the renal cortices afforded evidence of urinary excretion. Hence, the LD50 value considered to be >5000 mg/kg bw, when groups of 5 male and 5 female Wistar rats were treated with the given test chemical via oral gavage route.