Developmental toxicity of carboxylic acids to Xenopus embryos: a quantitative structure-activity relationship and computer-automated structure evaluation.

The developmental toxicity for each of 45 carboxylic acids was determined for Xenopus embryos. Acids tested included 12 unbranched, saturated aliphatics, 12 branched, saturated aliphatics, 12 unsaturated aliphatics, and 9 aromatics. Embryos were collected following hormone-induced breeding and exposed to at least eight concentrations of the acid, along with a control. For each concentration, 25 properly developing embryos were exposed to the acid solution for 96 h. Each acid was tested on at least three separate occasions and the data were pooled to calculate 96-h LC50 (lethality), 96-h EC50 (malformation), and DHI (developmental hazard index = 96-h LC50/96-h EC50) values. The endpoint data were subjected to quantitative structure-activity relationship (QSAR) analyse: and computer-automated structure evaluation (CASE). Variation in acid-induced lethality was effectively explained by partitioning and ionizability of the acids, while partitioning alone was somewhat effective in explaining variation for acid-induced malformation. The results indicated that developmental hazard of the acids to Xenopus embryos is primarily dependent on carbon-chain length, with acids containing five carbon atoms in the chain tending to be the most potent. Unsaturation reduced the hazard in comparison with the corresponding unbranched saturated acid. Developmental hazard was highest for 2-position branched compounds with a 5- or 6-C chain, but was reduced for 2-position branched acids with a 3- or 4-C chain. Hazard of the non-2 position branched acids was variable. Valproic (2-propylpentanoic) acid showed the highest developmental hazard with Xenopus, twice that of any other acid tested.

Quantitative structure-toxicity relationships and volume fraction analyses for selected esters.

The acute toxicity of aliphatic and aromatic mono and diesters in two eucaryotic organisms was compared. The test systems were the static 2-d Tetrahymena pyriformis 50% population growth impairment (IGC50(-1)) assay, and the flow-through 4-d Pimephales promelas 50% mortality (LC50(-1)) assay. In ciliates, esters act via the nonpolar narcosis mechanism of toxic action. This was indicated by: the high quality 1-octanol/water partition coefficient (log Kow) dependent quantitative structure-activity relationship (QSAR), log IGC50(-1) = 0.79 (log Kow) - 1.93, n = 15, r2 = 0.945, s = 0.22, f = 222.37 Pr > f = 0.001); volume fraction (Vf) (0.8e-02); and "a" coefficient (0.3) which are not different from other nonpolar narcotics. In vivo hydrolysis in Tetrahymena appears to be insignificant. However, in fish, presumably because of more active esterases, in vivo hydrolysis is significant and leads to greater toxicity of esters than observed for nonpolar narcotics. Moreover, it leads to a unique high quality QSAR, log LC50(-1) = 0.64 (log Kow) - 0.64, n = 14, r2 = 0.945, s = 0.22, f = 207.08, Pr > f = 0.0001). Due to in vivo hydrolysis, a nonreducing concentration gradient is formed between water and fish. Therefore, the fish take up more toxicant as compared to a situation that leads to thermodynamic equilibrium. Additional information about the mechanism of ester toxicity in fish was gained by applying corrections for hydrolysis in volume fraction analyses. The corrected Vf (0.6e-02) is very close to the one found for nonpolar narcotics (0.7e-02).(ABSTRACT TRUNCATED AT 250 WORDS)

Structure-toxicity relationships for alkanones and alkenones.

The relative toxicity (log IGC-1(50)) of 54 selected alkanones, both aliphatic and aromatic, as well as, alkenones and alkynones was evaluated in the static Tetrahymena pyriformis population growth assay. Excess toxicity, an indicator of bioreactivity, was associated only with the alpha-beta unsaturated alkenones and alkynones. Moreover, the alkynones were found to be more toxic than corresponding alkenones. A high quality 1-octanol/water partition coefficient (log Kow) dependent structure-toxicity relationship, log IGC-1(50) = 0.86 (log Kow) - 2.27; r2 = 0.955, was developed for alkanones. This QSAR represented the nonpolar narcosis mechanism of toxic action. Toxicity of alkenones was predicted by the highest-occupied-molecular-orbital energy (HOMO), log IGC-1(50) = -3.474 (HOMO) -35.357; r2 = 0.897, and the difference between HOMO and the lowest-unoccupied-molecular-orbital energy (LUMO), log IGC-1(50) = -3.559 (HOMO-LUMO gap) - 36.106; r2 = 0.903. The alpha-beta unsaturated ketones are considered soft electrophiles. Moreover, the toxicity of the aliphatic alkanones and alkenones was predicted by log Kow and LUMO, log IGC-1(50) = 0.69 (log Kow) - 2.55 (LUMO) + 0.05; r2 = 0.852.

Sexually abused children: identifying masked presentations in a medical setting.

Sexual abuse of children frequently lies hidden while the victims receive medical care for other complaints. To identify clinical signals of latent abuse, we studied 50 children whose initial presentations masked the presence of sexual abuse and compared them with 31 overt cases identified by chief complaint. A broad variety of symptoms masked the abuse. While some, such as early adolescent pregnancy and genital symptomatology, might have suggested the diagnosis, unusual physical symptoms, psychosomatic, and behavioral disorders were as frequent. The masked group differed significantly from the more frequently studied overt group in that chronic history of sexual abuse was twice as common; school problems and psychosomatic disorders were three times as frequent; the alleged abuser was more often an immediate family member, usually the father; male victims were more likely to present in this disguised manner. Familiarity with typical masked presentations should aid earlier identification of these troubled children.

Relactation by mothers of sick and premature infants.

Relactation, the induction of lactation at any time beyond the immediate postpartum period, has received minimal scientific investigation. In this study, one adoptive mother and six mothers ten to 150 days postpartum, who for a variety of reasons did not initiate or maintain lactation after delivery, attempted relactation. Each suckled her infant at regular feeding intervals. Prior to milk production, formula was provided during suckling through an artificial device. Serum prolactin responses to thyrotropin-releasing hormone infusion and to suckling were measured at the start of the study and to suckling at approximately weekly intervals thereafter. All mothers produced milk; three completely nourished their infants and two others provided at least half of their infants' nutritional needs. The adoptive mother and one other failed to provide significant quantities of milk. Mothers reached their maximum potential for milk production in varying periods of time (eight to 58 days). Shorter postpartum interval and less postpartum breast involution correlated with the likelihood of successful relactation and the rapidity of the onset of lactation. Basal prolactin levels and stimulation tests were of no additional predictive value. Each mother, regardless of milk production, expressed positive feelings about nurturing her infants in this manner. We conclude that relactation frequently is possible and may offer the mother of a sick or premature infant who desires to breast-feed an alternative if she does not maintain lactation in the immediate postpartum period.

Pediatric liaison psychiatry: a forum for separation and loss.

Separation and loss issues arise frequently in pediatric hospital settings. Three forms of psychiatry/psychology liaison are presented which demonstrate: 1. case-centered collaboration to address child and family concerns about death; 2. team-centered activities which link family and staff roles in the course of terminal illness; and 3. the development of a program mechanism to meet the needs of staff "survivors" of recurrent childhood deaths. These examples illustrate the enrichment which pediatric psychiatry/psychology liaison program offer when the conceptual model of liaison service and teaching operates flexibly on case, team, and program levels.

Breaking the cycle in abusive families.

The tendency for the cycle of abusive and neglectful parenting to be transmitted across generations has been well documented. The authors report on 40 families who broke this family pattern. The mechanisms for change used in these families included reliance on a broad network of resources, a degree of self-differentiation, an attitude of realistic optimism, and the ability to marshall extra resources to meet crisis situations. The authors recommend further study of such exceptions and a more hopeful approach to the problem of abusive families.

Antecedents of child abuse and neglect in premature infants: a prospective study in a newborn intensive care unit.

Families of premature and ill newborns admitted to a regional newborn intensive care unit were studied prospectively to assess the incidence of reported child abuse and neglect. Of the 255 infants discharged to their parents, ten were subsequently reported as victims of maltreatment during the first year of life. The high incidence of maltreatment (3.9%) in these premature and ill newborns supports the findings of retrospective studies that there is an increased risk of maltreatment in these special infants. Thirteen family psychosocial characteristics, assessed by admission interview, showed significant association with later maltreatment. These family characteristics included social isolation, a family history of child abuse and neglect, serious marital problems, inadequate child care arrangements, apathetic and dependent personality styles, and inadequate child spacing. Maltreated infants were less mature at birth and had more congenital defects than their nursery mates. There was also less family-infant contact during the prolonged nursery hospitalization in families in which maltreatment eventually occurred.