Pre- and postnatal studies on 2,4,5-trichlorophenoxyacetic acid, 2,4-dichlorophenoxyacetic acid and their derivatives in rats

Khera, K. S.; McKinley, W. P.

doi:10.1016/0041-008x(72)90221-9

Cited by 80 publications

(13 citation statements)

References 2 publications

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“…Phocomelia, amelia and syndactyly arc the manifestations of skeletal defects induced by the resins from marijuana in the rat [23], while shortened metacarpals and metatarsals are among the malformations observed in lambs from ewes exposed to the plant Veratrum californicum [2], The sternum is one region of the rat skeleton affected by the herbicides 2,4,5-T and 2.4-D [11] in a manner quite similar to the sternal damage observed in the present study. Of course, the effects of the drug thalidomide on the human embryo are well known [26], The carbonic anhydrase inhibitor, acetazolamide, has been shown to produce very specific defects in the postaxial portion of the forelimb of several rodents including the hamster [12,13].…”

Section: Discussionsupporting

confidence: 54%

Skeletal Malformations Resulting from Cadmium Treatment in the Hamster

Gale

Ferm

1973

Neonatology

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Previous studies have shown that cadmium induces a variety of grossly detectable malformations in the golden hamster including exencephaly, cleft lip and palate, amelia, micromelia and ectrodactyly. This report presents the frequency and types of underlying skeletal malformations induced by the intravenous administration of cadmium at four times during the critical stages in hamster embryo organogenesis. In general, all areas of the skeletal system are damaged by this heavy metal. This is manifested by the absence or poor development of ossification centers in different bones. Possible mechanisms of action of cadmium are discussed.

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Section: Discussionsupporting

confidence: 54%

Skeletal Malformations Resulting from Cadmium Treatment in the Hamster

Gale

Ferm

1973

Neonatology

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“…Kast (1994) indicated that wavy ribs do not seem to be strain-specific in rats, but Wistar rats generally have a higher background incidence of wavy ribs (2-22%) (Khera and McKinley, 1972;Khera et al, 1978;Buttar et al, 1978;Verma and Guna Sherlin, 2001;Favero et al, 2005) than do Sprague-Dawley (SD or CD s ) rats (0-1.5%) (Nishimura et al, 1982;Marathe and Thomas, 1986;Yoshimura and Delatour, 1986;Vorhees, 1987;Morseth and Nakatsu, 1991), although the incidence of wavy ribs may vary among Wistar populations (Nyitray and Druga, 1989). Wistar rats also may be more sensitive than SD rats to the induction of wavy ribs by exogenous exposures, although the data to compare strain effects is limited.…”

Section: Species Concordance and Divergencementioning

confidence: 95%

Interpretation of skeletal variations for human risk assessment: delayed ossification and wavy ribs

Carney

Kimmel²

2007

Birth Defects Research Pt B

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Delayed (or incomplete) ossification of developing fetal bones and wavy ribs are some of the most common skeletal variations encountered in regulatory guideline developmental toxicity studies. Although they tend to be regarded as minor effects, they can be quite sensitive and consequently may influence the study lowest-observed-adverse-effect levels (LOAELs), and thus, impact classification, labeling, and risk assessment. In this study, we review the underlying mechanisms of these skeletal variations, evaluate different scenarios in which they have been observed, offer guidance for their interpretation, and comment on their use for risk assessment. Both minor delays in ossification and wavy ribs seem to be readily repairable via postnatal skeletal remodeling, are not mechanistically linked to malformation, and often are seen in the presence of maternal or fetal toxicity. As such, these minor variations would not generally be considered adverse in and of themselves but should be interpreted in the context of other maternal and fetal findings, information available on normal skeletogenesis patterns, mode of action of the test agent, and historical control incidence using a weight of evidence approach. Birth Defects Res 80: 473-496, 2007. r 2007

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“…kg -1 to 24 mg . kg -1 b. w., from the 6th to the 15th day of pregnancy, and of Khera et al (1971) who treated rats with 2,4,-D and 2,4,5-T at doses of 100 mg . kg -1 and 150 mg .…”

Section: Discussionmentioning

confidence: 99%

“…Administration of aryloxyacetic acid-derivative herbicides during organogeny led to disorders in foetuses such as dropping eyelids, hydrocephalus, split hard palate, anomalies of the heart, kidneys, and skeleton Birnbaum et al 1989;Courtney et al 1970;Courtney and Moore 1971;Emerson et al 1970;Khera et al 1971;Loktionov and Tsyrempilov 1987;Vos et al 1974). …”

mentioning

confidence: 99%

Toxicity of hercides 2,4-D and MCPA for Rats and Rabbits

Kobal¹,

Budinha²

1999

Acta Vet. Brno

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Kobal S., M. V. Budihna: Toxicity of Herbicides 2,4-D and MCPA for Rats and Rabbits. Acta Vet. Brno 1999, 68: 281-290. A subacute toxicity test using 2,4-dichlorophenoxyacetic acid (2,4-D, 10 mg . kg -1 and 100 mg . kg -1 ) and 4-chloro-2-methylphenoxyacetic acid (MCPA, 15 mg . kg -1 and 150 mg . kg -1 ) was carried out on Wistar rats (n = 60) and New Zealand White rabbits (n = 30) of both sexes.The lower doses of 2,4-D and MCPA used in our experiments were chosen based on the estimate that such doses would be present in feed of plant origin treated with the concentrations of both herbicides recommended by the manufacturer; the higher ones were sublethal doses.Herbicides 2,4-D and MCPA in our trial did affect neither body weight in adult rats and rabbits and their offspring nor weights of inner organs or the red and white blood cell count. The mucous membrane of the stomach and small intestines in rats treated with high doses of both herbicides was slightly inflamed and swollen. In rabbits, some of the semen characteristics changed during the trial; both herbicides acted in different directions. At the end of the trial the concentration of serum testosterone was significantly higher (p < 0.05) in rabbits treated with MCPA than in controls. The number of surviving young per litter at weaning in the MCPA group of rabbits was lower than in controls. No evident toxic effects on the viability and the ossification processes were observed in the young of treated rabbits.

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Pre- and postnatal studies on 2,4,5-trichlorophenoxyacetic acid, 2,4-dichlorophenoxyacetic acid and their derivatives in rats

Cited by 80 publications

References 2 publications

Skeletal Malformations Resulting from Cadmium Treatment in the Hamster

Skeletal Malformations Resulting from Cadmium Treatment in the Hamster

Interpretation of skeletal variations for human risk assessment: delayed ossification and wavy ribs

Toxicity of hercides 2,4-D and MCPA for Rats and Rabbits

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