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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data have been obtained from secondary source.

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Toxicological Profile for dinitrophenol
Author:
M. Olivia Harris, M.A; James J. Corcoran, Ph.D. (peer rewied by Dr. martin Alexander; Dr.Leon Koller; Dr.Norman Trieff)
Year:
1995
Bibliographic source:
U.S Department of Health and human Services, Public Health Service Agency for Toxic Substances and Disease Registry
Reference Type:
review article or handbook
Title:
Teratology studies in mice with 2-set-butyl-4,6 dinitro phenol (Dinoseb).
Author:
Gibson JE.
Year:
1993
Bibliographic source:
Food Cosmet Toxicol 11:31-43.

Materials and methods

Principles of method if other than guideline:
The study measured important developmental toxicity and points, including teratogenicity.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
mouse
Strain:
Swiss Webster

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
Treatment was done on gestation day 10-12, than mice were sacrificed on gestation day 19.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0
Basis:
no data
mg/Kg/day
Remarks:
Doses / Concentrations:
25.5
Basis:
no data
mg/Kg/day
Remarks:
Doses / Concentrations:
38.3
Basis:
no data
mg/Kg/day

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Remarks:
25.5 mg/Kg/day
Basis for effect level:
other: maternal toxicity
Dose descriptor:
LOAEL
Remarks:
38.3 mg/Kg/day
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

In this study the lower dose 25.5 mg/Kg/day apparently did not produce maternal toxicity (NOAEL).

The high dose 38.3 mg/Kg/day produced overt toxicity (hyperexcitability and hyperthermia) in dams (data not presented), but no deaths (LOAEL).

The percentage resorption increased, but the effect was not significant or dose-related; no other abnormalities were observed.

Applicant's summary and conclusion

Conclusions:
The authors indicated that the high dose 38.3 mg/Kg/day produced overt toxicity (hyperexcitability and hyperthermia) in dams (data not presented), but no deaths. The percentage resorption increased, but the effect was not significant or dose-related; no other abnormalities were observed. Thus, treatment of mice at a dose level producing maternal toxicity did not result in adverse developmental effects.
Executive summary:

Data have been obtained from secondary source that mentions Gibson JE. 1973. Teratology studies in mice with 2-set-butyl-4,6 dinitro phenol (Dinoseb). Food Cosmet Toxicol 11:31-43. This study measured important developmental toxicity and points, including teratogenicity. Three doses 0, 25.5, 38.5 mg/Kg/day of 2,4 -dinitrophenol were administered by gavage to Swiss-Webster mice on gestaetion day 10 -12. On gestation day 19 mice were sacrified and important developmental toxicity end points, including teratogenicity observed. The authors indicated that the high dose 38.3 mg/Kg/day produced overt toxicity (hyperexcitability and hyperthermia) in dams (data not presented), but no deaths. The percentage resorption increased, but the effect was not significant or dose-related; no other abnormalities were observed. Thus, treatment of mice at a dose level producing maternal toxicity did not result in adverse developmental effects.