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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study did not follow OECD guidelines and was not performed under GLP. Only reports on the effect of KSCN on nutrient transport to the brain in pups. Only one dose level.

Data source

Reference
Reference Type:
publication
Title:
Diverse effects of mild and potent goitrogens on blood-brain barrier nutrient transport.
Author:
Raghunath, M. Bala, T. S.
Year:
1998
Bibliographic source:
Neurochem. Int., Volume 33, pp. 173-177

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
KSCN

Test animals

Species:
rat
Strain:
Wistar
Sex:
female

Administration / exposure

Route of administration:
oral: feed
Details on mating procedure:
females were mated with control males
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
8 weeks before and during gestation and lactation
Frequency of treatment:
daily via food
Details on study schedule:
- F1 parental animals not mated until ± 10 weeks after selected from the F1 litters.
- Selection of parents from F1 generation when pups were unknonw days of age.
- Age at mating of the mated animals in the study: ± 10-12 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
± 25 mg/rat/day
Basis:
nominal in diet
No. of animals per sex per dose:
unknown
Control animals:
yes, concurrent vehicle

Results and discussion

Results: P0 (first parental animals)

Effect levels (P0)

Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
no NOAEL identified Generation not specified (migrated information)

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Continuous feeding of KSCN to females through 2 generations at a level of 25 mg/rat per day, seems to have an adverse effect on the nutrient transport across the blood brain barrier in the F2 generation. However due to the limitations of the study a firm conclusion cannot be drawn.
Executive summary:

Populations living in goitre endemic areas consume foods rich in a variety of goitrogens of different potencies and some are severely hypothyroid. Recently we observed in Wistar:NIN rats that chronic feeding of KSCN to dams produced only a moderate hypothyroidism and decreased the transport of 2 -deoxy-D-glucose(2 -DG) across the blood-brain barrier (BBB) in the offspring. The present studies were conducted to assess whether severe hypothyroidism would have greater effect on BBB nutrient transport. It has now been observed that weaning the pups of KSCN fed dams on to KSCN diet for four weeks had no further effect either on their thyroid status or the BBB 2 -DG transport. However, feeding KSCN to rats through two generations produced somewhat severe hypothyroidism in F1 pups than that in F0 pups. Interestingly, unlike in F0 pups, the BBB transport of all the three nutrients tested (2 -DG, Leu and Tyr) was significantly decreased in F1 pups, albeit to a small extent (10 -15%). On the other hand the potent goitrogen, methyl mercaptoimidazole (MMI) even on short term feeding to pregnant dams produced very severe hypothyroidism in the offspring (Serum T4:0.55 ± 0.099 µg/dl vs 4.96 ± 0.85 in controls). Surprisingly, the BBB transport of 2 -DG, Leu, Tyr and also sucrose, the background marker, was significantly increased in these pups (20 -30%). The diverse effects of goitrogen induced moderate and severe hypothyroidism observed here on the BBB nutrient transport probably suggest different mechanisms for iodine deffciency disorders of different aetiologies and hence the need for discrete approaches for their management.