Evaluation of the effects of inhalation exposure to 1,3-dichloropropene on fetal development in rats and rabbits

Hanley, Thomas R.; John-Greene, J. A.; Young, John T.; Calhoun, L. L.; Rao, K. S.

doi:10.1016/0272-0590(87)90141-2

Cited by 16 publications

(6 citation statements)

References 7 publications

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“…Mixed isomer vapors of 1,3-dichloropropene were not embryotoxic or teratogenic in bred rats or inseminated rabbits exposed to 20, 60, or 120 ppm vapors, 6 h/day, during gestation days 6-15 (rats) or 6-18 (rabbits) (Hanley et al, 1987). Maternal toxicity was evidenced at all exposure levels.…”

Section: Effects On Reproductionmentioning

confidence: 87%

1,3-Dichloropropene

Stott

Gollapudi

2010

Hayes' Handbook of Pesticide Toxicology

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Section: Effects On Reproductionmentioning

confidence: 87%

1,3-Dichloropropene

Stott

Gollapudi

2010

Hayes' Handbook of Pesticide Toxicology

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“…No maternal effects were observed in an inhalation study with 1,2-dichlorobutene or in an oral gavage study with 1-hexene (Gingell et al, 2000;Kennedy et al, 1982). Maternal toxicity was, however, observed in rats and rabbits in an inhalation study with 1,2-dichloropropene at concentrations of 60 and 120 ppm administered on days 6 -15 (rats) or days 6 -18 (rabbits) of gestation (Hanley et al, 1987). Note.…”

Section: Discussionmentioning

confidence: 98%

Developmental Toxicity and Genotoxicity Studies of 1,1,1,3,3,3-Hexachloropropane (HCC-230fa) in Rats

Brock¹

2003

Toxicological Sciences

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The potential developmental toxicity and the in vitro and in vivo genotoxicity of HCC-230fa were assessed. In the developmental toxicity study, groups of 25 mated Crl:CD(R)(SD)BR rats were exposed (whole body) by inhalation to HCC-230fa over days 7-21 of gestation; the day of confirmed mating was designated as gestation day 1 (GD1). Exposures were 6 h per day at concentrations of 0, 0.5, 2.5, or 25 ppm. Body weight, food consumption, and clinical observation data were collected during the study. On day 22 of gestation, the dams were euthanized and examined grossly. The fetuses were removed and subsequently weighed, sexed, and examined for external, visceral, head, and skeletal alterations. Evidence of maternal and developmental toxicity was observed at 25 ppm and was noted as significant, compound-related reductions in mean maternal body weight, weight change, and food consumption. Significant fetal effects also were observed at 25 ppm as compound-related reductions in mean fetal weight and increased fetal malformations (filamentous tail, situs inversus, absent vertebrae) and variations (rudimentary cervical ribs, delayed sternebral ossification). There was no evidence of either maternal or developmental toxicity at 0.5 or 2.5 ppm. The genotoxicity of HCC-230fa was examined in a bacterial reversion assay and in erythrocyte micronucleus studies in two species by different routes of administration. No increases in the number of revertants were observed in the bacterial reversion assay. In one micronucleus study, HCC-230fa was administered by inhalation to rats as part of a 90-day study at doses indicated above. For the second study, ICR mice were given a single ip dose at 0, 166, 330, or 660 mg/kg. In both micronucleus studies, a significant increase in micronucleated erythrocytes was observed. The results of these studies suggest that HCC-230fa affects rapidly dividing cells and may have long-term consequences for occupational exposures.

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“…Fetal toxicity, as evidenced by reduced body weight and transient delayed ossification of the pubic bones, was observed in gestation day 20 rat fetuses at exposures > 10,000-fold human plasma levels. Delayed fetal skeletal ossification is commonly observed in teratology studies, may occur secondary to maternal toxicity (i.e., decreased body weight and/or food consumption), and is often transitory (Breslin, Kirk, and Zimmer 1989; Hanley et al 1987; Kirk et al 1995; Rodwell et al 1989). Rat postnatal evaluations (Skov et al 2004) further support the transient nature of this finding, because no effects were observed on the survival, skeletal development, or behavior of F 1 generation pups.…”

Section: Discussionmentioning

confidence: 99%

“…observed in teratology studies, may occur secondary to maternal toxicity (i.e., decreased body weight and/or food consumption), and is often transitory (Breslin, Kirk, and Zimmer 1989;Hanley et al 1987;Kirk et al 1995;Rodwell et al 1989). Rat postnatal evaluations (Skov et al 2004) further support the transient nature of this finding, because no effects were observed on the survival, skeletal development, or behavior of F1 generation pups.…”

Section: Safety Ratiosmentioning

confidence: 99%

Nonclinical Safety of Ziconotide: An Intrathecal Analgesic of a New Pharmaceutical Class

et al. 2007

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Ziconotide, a potent, selective, reversible blocker of neuronal N-type voltage-sensitive calcium channels, is approved in the United States for the management of severe chronic pain in patients for whom intrathecal therapy is warranted, and who are intolerant or refractory to other treatment, such as systemic analgesics, adjunctive therapies, or intrathecal morphine. In the European Union, ziconotide is indicated for the treatment of severe chronic pain in patients who require intrathecal analgesia. Nonclinical investigations of ziconotide included a comprehensive characterization of its toxicology, incorporating acute and subchronic toxicity studies in rats, dogs, and monkeys; reproductive toxicity assessments in rats and rabbits; and mutagenic, carcinogenic evaluations performed in vivo and in vitro. Additional investigations assessed the potential for cardiotoxicity (rats) and immunogenicity (mice, rats, and guinea pigs), and the presence or absence of intraspinal granuloma formation and local cell proliferation and apoptosis (dogs). The resulting nonclinical toxicology profile was predictive of human adverse events reported in clinical trials and consistent with ziconotide's pharmacological activity. Frequently observed nonclinical behavioral effects included tremoring, shaking, ataxia, and hyperreactivity. Occurrences were generally transient and reversible upon cessation of treatment, and intolerable effects occurred at doses more than 45 times the maximum recommended clinical dose. Ziconotide was not associated with target organ toxicity, teratogenicity, or treatment-related gross or histopathological changes; it displayed no mutagenic or carcinogenic potential and no propensity to induce local cell proliferation or apoptosis. Although guinea pigs developed systemic anaphylaxis, antibodies to ziconotide were not detected in mice, rats, or guinea pigs, indicating low immunogenic potential. No evidence of granuloma formation was observed with intrathecal ziconotide treatment. In summary, the results from these nonclinical safety assessments revealed no significant toxicological risk to humans treated with ziconotide as recommended.

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Evaluation of the effects of inhalation exposure to 1,3-dichloropropene on fetal development in rats and rabbits

Cited by 16 publications

References 7 publications

1,3-Dichloropropene

1,3-Dichloropropene

Developmental Toxicity and Genotoxicity Studies of 1,1,1,3,3,3-Hexachloropropane (HCC-230fa) in Rats

Nonclinical Safety of Ziconotide: An Intrathecal Analgesic of a New Pharmaceutical Class

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