Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Secondary source

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Mononitrophenols
Author:
International Programme on Chemical Safety (IPCS)
Year:
2011
Bibliographic source:
http://www.inchem.org/documents/cicads/cicads/cicad_20.htm (query result from 2011-10-14)
Reference Type:
study report
Title:
Unnamed
Year:
1983

Materials and methods

Principles of method if other than guideline:
A range-finding study on maternal and developmental toxicity was conducted in rats after repeated gavage of the test material during gestation.
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
2-nitrophenol
EC Number:
201-857-5
EC Name:
2-nitrophenol
Cas Number:
88-75-5
Molecular formula:
C6H5NO3
IUPAC Name:
2-nitrophenol
Details on test material:
- Name of test material (as cited in study report): 2-Nitrophenol
No further data is given on the test material.

Test animals

Species:
rat
Strain:
other: Charles River COBS CD

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
not specified
Details on exposure:
no data
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
no data
Duration of treatment / exposure:
from day 5 to day 15 of gestation
Doses / concentrations
Remarks:
Doses / Concentrations:
50, 125, 250, 500, and 1000 mg/kg bw
Basis:
other: not specified
No. of animals per sex per dose:
5 dams per group
Control animals:
other: yes (not further specified)

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes

BODY WEIGHT: Yes

POST-MORTEM EXAMINATIONS: Yes

OTHER: Urine, haircoat
Ovaries and uterine content:
- Uterine examination on day 20
Fetal examinations:
no data
Historical control data:
Yes

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes. Remark: dose levels of 500 and 1000 mg/kg body weight caused signs of maternal toxicity (transient but dose-related decrease in weight gain early during treatment).

Details on maternal toxic effects:
One high-dose animal died, but no cause of death could be determined. Other clinical findings included darkly coloured urine at > 250 mg/kg body weight and yellow staining of haircoat (at the nose, mouth, anogenital area) at > 125 mg/kg body weight; the necropsy findings gave no biologically meaningful differences in surviving dams. At the highest dose level of 1000 mg/kg body weight, a slight but statistically significant (also compared with historical controls) increase in group mean post-implantation losses (13.8 % versus 8.2 % in controls) and mean early resorptions (2.3 versus 1.2 in controls) was seen.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
125 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
No effects were observed on the number of viable fetuses, implantations, or corpora lutea.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion