Professional Documents
Culture Documents
Diphenyl Ethers
And
Developmental Toxicity
Inhibit photosynthesis
Inhibit electron transport
Inhibit coupled photophosphorylation?
Some auxin-like action
Inhibit protoporphyrinogen oxidase
Last common enzyme in synthesis of chlorophyll
and hemoglobin
(some diphenyl ethers may affect hemoglobin
production , as shown by gray color of treated
mice)
Menghambat fotosintesis
Uses
Water solubility
Persistence
Not very great
Toxicology
LD50 po in rats
EPA: 1,300 mg/kg
UI Extension: 3,300 mg/kg
Kegunaan
Kelarutan air
Kegigihan
Tidak terlalu besar
Toksikologi
LD50 po pada tikus
EPA: 1.300 mg / kg
Ekstensi UI: 3.300 mg / kg
Oxyfluorfen
Water solubility: 0.1 ppm
Bioaccumulation quite probable under normal
use
Herbicidal activity
2-4 months (in medium-textured IL soil)
Pre- and post-emergent herbicide
Broad range of crops
Most uses cancelled in 1982
Kelarutan dalam air: 0,1 ppm
Diperkirakan tidak ada potensi bioakumulasi
Aktivitas herbisida
2-4 bulan (di tanah bertekstur IL sedang)
Herbisida pra-dan pasca-muncul
Luas tanaman
Sebagian besar penggunaan dibatalkan pada tahun 1982
Oxyfluorfen toxicology
Acute
LD50, po, in rats: 5,000 mg/kg
Delayed effects
Probable mutagen
Probable carcinogen
Contaminated with perchloroethylene
Probable hepatotoxicant
Probable thyrotoxicant
Develomental toxicity data inadequate
Akut
LD50, po, dalam tikus: 5.000 mg / kg
Efek tertunda
Kemungkinan mutagen
Kemungkinan karsinogen
Terkontaminasi dengan perchlorethylene
Kemungkinan hepatotoksis
Mungkin tirotoksik
Data toksisitas develomental tidak memadai
Uses:
Bifenox Paddy rice
Pre-emergent
Corn, soybeans
Toxicity
LD50, po, in rats:
UI Extension: 1,630
EPA: 6,400 mg/kg
Delayed toxicities
Carcinogen??
Ecotoxicology
Benign
Kegunaan:
Padi sawah
Pra-muncul
Jagung, kedelai
Toksisitas
LD50, po, pada tikus:
Ekstensi UI: 1,630
EPA: 6,400 mg / kg
Toksisitas tertunda
Karsinogen ??
Ekotoksikologi
Jinak
Bifenox
Nitrofen
Kelompok ke-2 pada cincin nitrofenil dari bifenox
bertindak sebagai degradophore
Brief History of Nitrofen
6 7 8
Protocol for 2-Generation Assay
F0: parental animals
2nd mating
Necropsy F2B at
Necropsy at F2B weaning; including
weaning F2A
complete histopathology
Continue feeding chemical to each group at the appropriate dosing level throughout the study (progeny, too!)
Advantages of the 2-Generation Assay
A single assay identifies:
acute or cumulative toxicity leading to
male or female infertility,
pre- and post-natal mortality,
pre- and post-natal growth retardation,
functional deficits in offspring
transplacental carcinogenesis
infertility
behavioral anomalies
The 2-Generation Assay:
Disadvantages
Cost
well over $500,000 per species
but still cheaper than the alternatives
Labor-intensive
Necropsies of all parents
Necropsies of offspring of all litters
Histopathology of offspring from 2nd litters
Identifies the existence of a problem, but not necessarily
its nature
Advantages of the 2-Generation Assay
A single assay identifies:
acute or cumulative toxicity leading to
male or female infertility,
pre- and post-natal mortality,
pre- and post-natal growth retardation,
functional deficits in offspring
transplacental carcinogenesis
infertility
behavioral anomalies
The 2-Generation Assay:
Disadvantages
Cost
well over $500,000 per species
but still cheaper than the alternatives
Labor-intensive
Necropsies of all parents
Necropsies of offspring of all litters
Histopathology of offspring from 2nd litters
Identifies the existence of a problem, but not necessarily
its nature
Chemically induced birth defetcs
Vary with
Chemical
Genotype
Of dam and of embryo
Within and between species
Developmental stage at time of exposure
Dose
Either severity of defects or probability of defect increases with
increasing dose
Karnofskys Law
Any chemical, given at the right time, and at the right dose,
to the right species will cause malformations
The fact that a pesticide causes malformations in one
species - especially at high doses - is not necessarily
enough reason to ban it.
In the case of nitrofen, malformations occurred in both rats
and mice, but not in rabbits.
Developmental Toxicity is a Threshold
Phenomenon
For agents other than mutagens, there is a minimum dose
that will not affect the embryo
because it is metabolized by the dam and does
not reach the embryo, and/or
it does not significantly perturb embryonic
development, and/or
compensatory mechanisms result in repair of
the damage.
Nitrofen
Causes malformations
In both rats and mice
Heart
Kidneys
Diaphragm
Eyes
At a fraction of the adult LD50
NOAEL in rats estimated at 0.03 mg/kg/day