Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Deficiency: Yes. Maternal toxicity not evaluated.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
maternal effects not stated, treatment period longer than required (2 ½ months plus gestation)
GLP compliance:
not specified
Limit test:
no

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:
Hypochloric acid
Purity: the chlorine gas to produce the hypochlorite solutions is described as "ultra high purity"

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
Age/weight at study initiation: Mature, 225-250 g

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
not stated
Duration of treatment / exposure:
2 1/2 months, prior to and throughout gestation
Frequency of treatment:
ad libitum
Duration of test:
2 1/2 months, prior to and throughout gestation
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 1, 10, 100 ppm corresponding to approximately 0, 0.08, 0.8, 8.0 mg/kg bw/day (assuming a water intake of 25 mL/rat/day and a body weight of 320 g)
Basis:
nominal conc.
No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle
Details on study design:
Sex: female

Examinations

Maternal examinations:
not determined
Ovaries and uterine content:
Examination of uterine content: Number of resorptions
Fetal examinations:
No. of dead Foetuses, Foetal Weight
Skeletal Yes
Soft tissue Yes

Statistics:
Chi-square analysis

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:not examined

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There was no treatment related effect on viability, external appearance and foetal weight. The percentage of skeletal, soft-tissue and total defects (combined skeletal and soft-tissue) was calculated and presented in the table. The foetuses from the 10 and 100 mg/L groups had a higher percentage of skeletal defects compared with control. However, these did not achieve statistical significance. The highest dose group also showed a higher rate of soft-tissue defects, again without achieving statistical significance when compared to control by chi-square analysis. These defects consisted of three cases of adrenal agenesis, one right-sided heart, one case of improper orientation of the apex of the heart, and one atrio-ventricular valve enlargement. Total defects were statistically higher in the high dose group than in control, whereas the lowest dose produced a lower percentage of defects than control.

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEL
Effect level:
>= 5.7 mg/kg bw/day
Basis for effect level:
other: teratogenicity
Dose descriptor:
LOAEL
Effect level:
> 5.7 mg/kg bw/day
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Effect of chlorine in drinking water on the formation of skeletal and soft-tissue defects in rat foetuses.

Concentration [ppm]

Skeletal defects [%]a

Soft-tissue defects [%]a

Total defects [%]a

0

34.5

7.1

21.1

1

23.8

0.0

12.2

10

59.1

0.0

27.1

100

57.7

19.2

38.5b

a            Values represent % of defects for all foetuses in each treatment

b            Statistically different from control (p < 0.05), chi-square analysis

Applicant's summary and conclusion

Conclusions:
A NO(A)EL for embryotoxic / teratogenic effects of >= 100 ppm corresponding to 5.7 mg/kg bw/day and a LO(A)EL for embryotoxic / teratogenic effects of > 100 ppm corresponding to 5.7 mg/kg bw/day were found.
Executive summary:
There were no treatment-related changes in viability, foetal weights and external appearance of all foetuses in all dose groups. Skeletal and soft-tissue defects were in the normal range for all dose groups. If skeletal and soft-tissue defects were combined a statistically significant increase was observed in the highest dose group. In the absence of a clear dose response and a relatively high incidence of defects in control animals, these findings were not considered to be of relevance. The authors conclude that chlorinated drinking water at the tested concentrations is relatively harmless to the rat when fed to pregnant dams. Unfortunately maternal toxicity was not evaluated. However, subchronic studies show that the NOAEL is 50 mg/kg bw/day.

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