2,4-dinitrophenol

Developmental toxicity / teratogenicity

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

Reference

Reference 1

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 2

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

Test material information

Constituent 1

Reference substance name:

2,4-dinitrophenol

EC Number:

200-087-7

EC Name:

2,4-dinitrophenol

Cas Number:

51-28-5

Molecular formula:

C6H4N2O5

IUPAC Name:

2,4-dinitrophenol

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 / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0
Basis:
no data
mg/Kg/day

Doses / concentrations 2

Remarks:

Doses / Concentrations:
25.5
Basis:
no data
mg/Kg/day

Doses / concentrations 3

Remarks:

Doses / Concentrations:
38.3
Basis:
no data
mg/Kg/day

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Remarks:

25.5 mg/Kg/day

Basis for effect level:

other: maternal toxicity

Remarks on result:

other: no futher information available

2

Dose descriptor:

LOAEL

Remarks:

38.3 mg/Kg/day

Basis for effect level:

other: developmental toxicity

Remarks on result:

other: no further information available

Results (fetuses)

Effect levels (fetuses)

Remarks on result:

other: see results reorted below

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.