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Toxicological information

Toxicity to reproduction: other studies

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Administrative data

Endpoint:
toxicity to reproduction: other studies
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Mechanisms regulating toxicant deposition to the embryo during early pregnancy: an interspecies comparison
Author:
Carney EW, Scialli AR, watson RE, deSesso JM
Year:
2005
Bibliographic source:
Birth Defects Research (Part C) 72, 345-360

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
Determination of salicylate concentration in maternal and foetal tissues on intravenous administration.
GLP compliance:
not specified
Type of method:
in vivo

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
not specified
Sex:
female

Results and discussion

Any other information on results incl. tables

Administration of salicylate to pregnant rats by intravenous infusion was associated with five-fold higher concentrations to total salicylate in maternal plasma than in the embryo, visceral sac, or extraembryonic fluid on GD 12.5. However, the proportion of free salicylate was slightly higher in the embryo than in maternal blood, consistent with ion trapping. By contrast, at term, total maternal plasma salicylate was only about twice the level of fetal blood salicylate.

The authors attributed the lower maternal:fetal salicylate ratio at term to decreased maternal protein binding closer to term, with free salicylate levels increasing from 14 to 27% between GD 12.5 and GD 20.5.

Applicant's summary and conclusion

Executive summary:

In rats, salicylic acid transfer across the placenta appears to be influenced both by ion trapping and protein binding. Clearance of salicylate from the near-term fetus across the placenta to the more alkaline maternal compartment is greater than maternal transfer to the fetus. This phenomenon can be augmented by alkalinization of maternal blood. Administration of salicylate to pregnant rats by intravenous infusion (to maintain constant maternal blood levels) was associated with five-fold higher concentrations to total salicylate in maternal plasma than in the embryo, visceral sac, or extraembryonic fluid on GD 12.5. However, the proportion of free salicylate was slightly higher in the embryo than in maternal blood, consistent with ion trapping. By contrast, at term, total maternal plasma salicylate was only about twice the level of fetal blood salicylate. The authors attributed the lower maternal:fetal salicylate ratio at term to decreased maternal protein binding closer to term, with free salicylate levels increasing from 14 to 27% between GD 12.5 and GD 20.5.

The distribution of salicylate in near-term human pregnancy favours the fetus, with neonatal:maternal salicylate concentration ratios of about 1.6. The concentration gradient of high concentrations in the fetus relative to the mother was attributed to greater protein binding in the term fetus, with comparable concentrations of free salicylate in the two compartments.