Registration Dossier

Administrative data

Endpoint:
specific investigations: other studies
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No guidelines or GLP compliance stated.

Data source

Reference
Reference Type:
publication
Title:
Sodium chlorite administration in Long-Evans rats: Reproductive and Endocrine Effects
Author:
Carlton BD, Habash DL, Basaran AH, George EL and Smith MK
Year:
1987
Bibliographic source:
Environmental Research, 42: 238-245

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Long-Evans rats were given access to 0, 1, 10 and 100 mg/L sodium chlorite in deionised water ad libitum as drinking water. Males were exposed 56 days, and females 14 days prior to breeding and throughout the 10-day breeding period. Adult males were necropsied after breeding. Dams and pups were necropsied at weaning and examined for thyroid hormone levels T3 and T4.
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Long-Evans
Sex:
male/female
Details on test animals and environmental conditions:
Source:Charles River Breeding Laboratories (Portage, Mich. USA)Age at study initiation:4-6 weeksMating ratio: Male:female – 1:2, Duration of mating: 10 daysDuration of exposure before mating: Males: 56 days; Females: 14 days

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
The study was conducted in the form of 3 experiments:•Experiment 1 was conducted to confirm the effect of chlorite on reproductive outcome.•Experiment 2 was conducted to confirm subtle reproductive effects observed during the first study.•Experiment 3 was conducted to reconfirm the observed reproductive effects and establish a NOEL if possible.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Experiment 1:Males: 56 days prior to breeding and then throughout 10 day breeding period.Females: 14 days prior to breeding and then throughout breeding, gestation and lactation until the pups were weaned on day 21.Experiment 2: 72-76 days for malesExperiment 3: duration not specified
Frequency of treatment:
Drinking water supplied ad libitum
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:Experiment 1: 0, 1, 10 and 100 mg sodium chlorite/L (0, 0.75, 7.5 and 75 mg chlorite/L)Basis:nominal in water
Remarks:
Doses / Concentrations:Experiment 2: 0, 100 and 500 mg sodium chlorite/L (0, 75 and 373 mg chlorite/L)Basis:nominal in water
Remarks:
Doses / Concentrations:Experiment 3: 0, 10 and 100 mg sodium chlorite/L (0, 7.5 and 75 mg chlorite/L)Basis:nominal in water
No. of animals per sex per dose:
Experiment 1: 12 males/dose group, 24 females/dose groupExperiment 2: 12 male rats/ dose groupExperiment 3: 12 male rats/ dose group
Control animals:
yes, concurrent vehicle

Examinations

Examinations:
BODYWEIGHTWATER CONSUMPTIONThree times per weekTHYROID HORMONE LEVELSMale pups examined on: Postnatal days 17, 21 and 40.Female pups examined on: Postnatal days 21 and 40.Adult females: Day 21 of lactationOTHER EXAMINATIONSFemales: fertility, length of gestation, body weight gain, maternal behaviourLitters: viability, litter size, day of eye opening, body weight gain, gross external abnormalitiesNecropsy: Adult males: complete blood count, and gross necropsy: reproductive tract (including testis, epididymis, prostate and seminal vesicles) weighed and subjected to histopathologic evaluation. Sperm motility.Dams: (lactation day 21) – complete blood count hormone analysis and complete gross necropsy: reproductive tract weighed and subjected to histopathologic evaluation.Pups: blood counts and hormone analysis, organ weights (reproductive tract)

Results and discussion

Details on results:
PARENT MALESNo significant changes in hormone levels or other observations made.PARENT FEMALESNo significant changes in hormone levels or other observations made.F1 MALESDecrease in serum T3 and T4 observed in 100 mg/L dose group only.F1 FEMALESDecrease in serum T3 and T4 observed in 100 mg/L dose group only.OTHER4.2Other In all studies, neither body weights nor water consumption were different between the 0, 1, 10 and 100 mg/L dose group animals. Water consumption among 500 mg/L animals was decreased throughout the dosing period by 20 %. The observed fertility rates varied between 67 and 96 % but did not differ in a dose dependent manner.No compound related abnormalities were found upon gross pathologic or histopathologic examinations. Haematologic parameters and organ and body weights were also unchanged in chlorite exposed rats.Sperm count and percentage of sperm motility were unaltered by chlorite exposure. However, sperm direct progressive movement was significantly reduced at 100 and 500 mg/L.A significant increase in abnormal sperm forms was observed among 100 and 500 mg/L dose group rats. The most commonly observed morphologic abnormalities were frayed tails, open hooks and amorphous sperm heads.LO(A)EL100 mg/L: altered thyroid hormone levels in offspringParent males:>100 mg/LParent females:>100 mg/LF1 males:100 mg/L: altered thyroid hormone levelsF1 females:100 mg/L: altered thyroid hormone levelsNO(A)ELParent males:≥ 100 mg/LParent females:≥ 100 mg/LF1 males:10 mg/LF1 females:10 mg/L

Applicant's summary and conclusion

Conclusions:
The results of this study suggest that the young rat is more sensitive to the antithyroid effects of chlorite than is the adult. Decreases in serum T3 and T4 were observed on postnatal days 21 and 40 in male and female pups exposed to 100 pm sodium chlorite.
Executive summary:

Long-Evans rats were given access to 0, 1, 10 and 100 mg/L sodium chlorite in deionised water ad libitum as drinking water. Males were exposed 56 days, and females 14 days prior to breeding and throughout the 10-day breeding period. Adult males were necropsied after breeding. Dams and pups were necropsied at weaning and examined for thyroid hormone levels T3 and T4. The results of this study suggest that the young rat is more sensitive to the antithyroid effects of chlorite than is the adult. Decreases in serum T3 and T4 were observed on postnatal days 21 and 40 in male and female pups exposed to 100 pm sodium chlorite.