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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Defciencies: Yes.No data on haematological examinations, results of drinking water intake not reported, no individual animal data.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1986

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
Version / remarks:
(methods comparable)
Deviations:
yes
Principles of method if other than guideline:
haematological results and drinking water intake not reported
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium hypochlorite
EC Number:
231-668-3
EC Name:
Sodium hypochlorite
Cas Number:
7681-52-9
Molecular formula:
ClO.Na
IUPAC Name:
sodium hypochlorite
Details on test material:
Sodium hypochlorite

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals or test system and environmental conditions:
7 weeks old169-172 g (mean group weights, males)119-120 g (mean group weights, females)

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on oral exposure:
Concentration in vehicle:0, 0.025, 0.05, 0.1, 0.2 0.4 % (0, 12.5, 25, 50, 100, 200 mg/kg bw/day for males and 14.3, 28.6, 57.2, 114.4, 228.8 mg/kg bw/day for females assuming a water consumption of 25 mL/day for a rat and a body weight of 500 and 350 g)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 days
Frequency of treatment:
ad libitumDaily (drinking water)
Doses / concentrations
Remarks:
Doses / Concentrations:0, 0.025, 0.05, 0.1, 0.2 0.4 % (0, 12.5, 25, 50, 100, 200 mg/kg bw/day for males and 14.3, 28.6, 57.2, 114.4, 228.8 mg/kg bw/day for females assuming a water consumption of 25 mL/day for a rat and a body weight of 500 and 350 g).Basis:no data
No. of animals per sex per dose:
number of animals per group: 10 per sex
Control animals:
yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:
Clinical signsYes (daily)MortalityYes (daily)Body weight Yes (weekly)Water consumption Yes (weekly)HaematologyYes( blood samples were taken at study termination; however, no further information is provided)
Sacrifice and pathology:
Organ Weights Yes, for all surviving animalsorgans: liver, kidneys, adrenals, testes, ovaries, spleen, brain, heart, pituitary gland, salivary glands, lungs.Gross and histopathologyYes, for all surviving animalsorgans: liver, kidneys, adrenals, testes, ovaries, spleen, brain, heart, pituitary gland, salivary glands, lungs.
Other examinations:
none
Statistics:
The data were subjected to analyses of variance and differences between the means were tested by Student’s t-test.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
Clinical signsEmaciationMortalityNo mortalities at any doseBody weight gainBody weight gain was statistically significantly reduced in males of the 0.2 and 0.4 % groups and in females of the 0.4 % group. Please refer to Table.HaematologyBlood samples were taken at study termination; however, no results of the examination are provided.Clinical chemistryBlood samples were taken at study termination; however, no results of the examination are provided.UrinalysisBlood samples were taken at study termination; however, no results of the examination are provided.Organ weightsHigh-dose males: absolute weights of lung, liver and spleen were significantly lower than controls.High-dose females: absolute weights of salivary glands, lung, heart and brain were significantly lower than controls.Gross and histopathologyBiochemical examination showed signs of damage to the liver in the 0.2 and 0.4 % groups of both sexes.

Effect levels

open allclose all
Dose descriptor:
LOAEL
Effect level:
100 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
other: (assuming a water consumption of 25 mL/day for a rat and a body weight of 500 g)based in reduced body weight gain and histopathological liver changes.
Dose descriptor:
LOAEL
Effect level:
114.4 mg/kg bw/day (nominal)
Sex:
female
Basis for effect level:
other: (assuming a water consumption of 25 mL/day for a rat and a body weight of 350 g)based in reduced body weight gain and histopathological liver changes.
Dose descriptor:
NOAEL
Effect level:
50 mg/kg bw/day (nominal)
Sex:
male
Basis for effect level:
other: (assuming a water consumption of 25 mL/day for a rat and a body weight of 500 g)
Dose descriptor:
NOAEL
Effect level:
57.2 mg/kg bw/day (nominal)
Sex:
female
Basis for effect level:
other: (assuming a water consumption of 25 mL/day for a rat and a body weight of 350 g)

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Mean body weights

Test substance concentration
(% NaOCl)

Mean body weights [g]

Males in week

Females in week

0

2

13

0

2

13

[g]

% of control

[g]

% of control

0 (control)

169

228

347

100

119

143

183

100

0.025

172

228

336

97

119

141

180

98

0.05

171

224

336

97

120

139

186

101

0.1

172

213

321

93

119

140

180

98

0.2

168

173

281

81

119

127

177

96

0.4

169

116

185

53

119

92

127

69

Applicant's summary and conclusion

Conclusions:
LO(A)EL: 0.2 %,corresponding to 100 mg/kg bw/d (males) and 114.4 mg/kg bw/d (females)(assuming a water consumption of 25 mL/day for a rat and a body weight of 500 and 350g)based in reduced body weight gain and histopathological liver changes.NO(A)EL: 0.1 %,corresponding to 50 mg/kg bw/d (males) and 57.2 mg/kg bw/d (females)(assuming a water consumption of 25 mL/day for a rat and a body weight of 500 and 350g)
Executive summary:

There were no mortalities throughout the study. Body weight gain was statistically significantly reduced in males of the 0.2 and 04 % groups and in females of the 0.4 % group. At autopsy there were no obvious macroscopic changes in any group, although several animals, particularly in the high dose, appeared emaciated. Absolute weights of the lung, liver and spleen of males and the salivary gland, lung, heart and brain of females were significantly lower in the highest-dose groups than in controls. No histological changes attributable to sodium hypochlorite administration were found in any of the experimental groups, but biochemical examination of the sera showed signs of slight damage to the liver in the two highest dose groups in both sexes.

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