4-chlorophenol

Toxicity to reproduction: other studies

Administrative data

Endpoint:

toxicity to reproduction: other studies

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

1991

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Documentation insufficient for assessment; non-standard test systems.

Data source

Reference

Reference Type:

publication

Title:

In vivo and in vitro structure-dosimetry-activity relationships of substituted phenols in developmental toxicity assays.

Author:

Kavlock RJ, Oglesby L, Hall LL et al.

Year:

1991

Bibliographic source:

Reprod Toxicol. 5:255-258.

Materials and methods

Principles of method if other than guideline:

Evaluation of structure-dosimetry-activity relationships (SDARs).

GLP compliance:

not specified

Type of method:

other: in vivo /in vitro

Test material

Test material information

Constituent 1

Reference substance name:

4-chlorophenol

EC Number:

203-402-6

EC Name:

4-chlorophenol

Cas Number:

106-48-9

Molecular formula:

C6H5ClO

IUPAC Name:

4-chlorophenol

Administration / exposure

Doses / concentrations

Remarks:

Doses / Concentrations:
in vivo test: 1000 mg/kg - max. maternal dose
Basis:
nominal conc.

Results and discussion

Any other information on results incl. tables

Results:

 

The potential to induce embryotoxicity in vitro was not well correlated with the potential to induce developmental toxicity in vivo: whereas the in vitro data demonstrates that the phenols are intrinsically embryotoxic, few of them actually produced significant developmental toxicity in the in vivo system, and there were few positive correlations between effects observed in the two systems.

 

Embryonic dosimetry obtained for the in vitro assay system indicated that the principal determining factor in producing embryotoxicity of a phenol in vitro is the ability to gain access into the embryo, but that once in the embryo, the lipophilic phenols are more toxic on a per molecule basis. Furthermore, embryonic dosimetry data for two phenols indicated that for a given exposure, in vitro embryos will accumulate more of a phenol than will the in vivo embryos.

So, in contrast to the in vivo findings, where few of the phenols actually produced developmental toxicity at a maximum maternal dose of 1000 mg/kg, all 13 phenols tested in vitro produced embryotoxicity (measured as growth retardation or as the incidence of structural abnormalities), with effective concentrations generally less than 0.5 mM.

 

In summary, the authors have undertaken a systematic study of the response of in vivo and in vitro embryos to a series of structural analogues, and attempted to relate the potency of the congeners to specific physicochemical properties. While different conclusions were reached about the potency of the phenols in the two systems, the assessment of pharmacokinetic parameters provided insight into the deposition and activity of these congeners in the embryo and have pointed us in the direction of determining the reason(s) for the differences that were observed.

 

This material was presented at the symposium entitled "Application of Pharmacokinetics in Developmental Toxicity Risk Assessments" held in conjunction with the 1990 meeting of the Society of Toxicology.