Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
August 9 1984 - August 23 1984
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study performed to GLP and guideline. The chlorinated isocyanurates (sodium dichloroisocyanurate and sodium dichloroisocynaurate dihydrate) produce free available chlorine, in the form of hypochlorous acid (HOCl) as they dissolve in water. As the equilibria involve all of the possible chlorinated isocyanurates, the toxicity of sodium dichloroisocyanurate (NaDCC) and sodium dichloroisocyanurate dihydrate (NaDCC.2H2O) will be virtually equivalent at the same available chlorine concentration. The parent compound for all chlorinated isocyanurates is isocyanuric acid (cyanuric acid). All of the chlorinated isocyanurates are essentially equivalent, once they are dissolved in water at the low concentrations at which they are used. Therefore read across from sodium dichloroisocyanurate dihydrate to troclosene sodium is justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Dichloroisocyanuric acid, sodium salt, dihydrate

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Kingston, New York, USA
- Weight at study initiation: 200.4 – 234.7 g
- Housing: Suspended wire mesh cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: No less than 7 days


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 150, 200, 250, 300 and 400 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg



DOSAGE PREPARATION: The test material was first put through a 40 mesh sieve and then the appropriate amount of test material was weighed on an electronic balance and transferred to a beaker. A small amount of corn oil was first added to make a paste and then the remaining required amount of vehicle was added to the beaker and stirred on a magentic stirrer for approcimately 5 to 10 minutes.


Doses:
Range finding study: 500, 1000, 1250, 1500 and 2000 mg/kg bw
Main study: 1500, 2000, 2500, 3000 and 4000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: All of the rats were observed for signs of toxicity and pharmacologic effects at 1, 2 and 3 hours post does, and once daily thereafter for 14 consecutive days. .
- Frequency of observations and weighing: Mortality and moribundity was recorded twice daily. Individual body weights were recorded prior to treatment, on day 7 and at death or termination
- Necropsy of survivors performed: yes
Statistics:
The mortality data were anlayzed for the males and the sexes by a logit regression method (Bliss, 1952) and for the females by a modified Behrens-Reed-Muench Method (Thakur and Fezio, 1981).

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
2 094 mg/kg bw
95% CL:
1 551 - 2 636
Sex:
female
Dose descriptor:
LD50
Effect level:
1 671 mg/kg bw
95% CL:
1 423 - 1 962
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 823 mg/kg bw
95% CL:
1 479 - 2 166
Mortality:
Cumulative mortality data for the range finding study are presented in table 1. The group 5 animal was found dead on day 3 post dose. No mortality occurred in the groups 1-4 animals. Cumulative mortality data for the main study are presented in table 2.
Clinical signs:
A variety of commonly noted clinical signs were observed in all groups with severity increasing with increasing dose.
Body weight:
In general animals which survived through termination gained weight, and animals which were found dead lost weight after initiation.
Gross pathology:
Animals which survived to termination showed no observable gross pathology findings. Gross pathology findings in found dead animals included observations in the stomach, intestines, lung, liver and abdominal cavity

Any other information on results incl. tables

Table 1: Cumulative mortality (range finder)

Group

Dose level (mg/kg)

Hours

Days

1

2

4

1

2

3

4

1

500

0

0

0

0

0

0

0

2

1000

0

0

0

0

0

0

0

3

1250

0

0

0

0

0

0

0

4

1500

0

0

0

0

0

0

0

5

2000

0

0

0

0

0

1

1

Table 2: Cumulative mortality data (main study)

Group

Dose level (mg/kg)

Hours post dose

Day post dose

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

 

 

 

 

 

Males

1

1500

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

2000

0

0

0

2

2

2

3

3

3

3

4

4

4

4

4

4

4

3

2500

0

0

0

1

2

2

2

2

2

3

3

4

4

4

4

4

4

4

3000

0

0

0

1

3

3

3

3

3

3

3

3

3

3

3

3

3

5

4000

0

0

0

2

4

4

4

4

4

4

5

5

5

5

5

5

5

 

 

 

 

 

Females

 

1

1500

0

0

0

0

1

1

1

1

1

1

1

1

1

1

1

1

1

2

2000

0

0

0

3

5

5

5

5

5

5

5

5

5

5

5

5

5

3

2500

0

0

0

4

5

5

5

5

5

5

5

5

5

5

5

5

5

4

3000

0

0

0

4

5

5

5

5

5

5

5

5

5

5

5

5

5

5

4000

0

0

0

3

4

5

5

5

5

5

5

5

5

5

5

5

5

The study was performed on sodium dichloroisocyanurate dihydrate. In order to convert the LD50 values to the anhydrous form the following calculation is applied:

Lowest LD50 = 1671 mg/kg (females)

MW of sodium dichloroisocyanurate dihydrate = 256

MW of sodium dichloroisocyanurate anhydrous = 220

220/256 x 1671 = 1436 mg/kg

Therefore the LD50 value for sodium dichloroisocyanurate anhydrous is 1436 mg/kg

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Sodium dichloroisocyanurate dihydrate is harmful by the oral route based on the LD50 value of 1671 mg/kg bw.
Sodium dichloroisocyanurate anydrous is harmful by the oral route based on the calculated LD50 value of 1436 mg/kg bw