Postnatal evolution of supernumerary ribs in rats after a single administration of sodium salicylate.

Radiographs were used to follow the postnatal evolution of 14th ribs in rat pups. Initially, 30 pregnant female rats were randomly distributed into two groups receiving 0 or 300 mg kg(-1) sodium salicylate on day 9 of pregnancy. In the treated group, adverse effects were noted on body weight changes and food consumption during the 2 days following dosing. At birth, a high majority of pups had extra ribs at the 300 mg kg(-1) dose. Radiographs done on postnatal days 1, 6, 14, 28 and 54 showed a reduction in the incidence of rudimentary ribs only, whereas extra ribs, often associated with 27 presacral vertebrae, had the same incidence from birth to adult stage. Furthermore, extra ribs seemed to exhibit similar growth evolution to the other thoracic ribs. This work helps to clarify the postnatal evolution of supernumerary ribs because it was performed on the same animals from birth to adult stage, showing that the reversibility was related to rib length and, in consequence, concerned the rudimentary ribs only. The coexistence of additional presacral vertebrae primarily with extra ribs suggests that both kinds of supernumerary ribs (rudimentary and extra) might be different phenomena and could be considered separately in developmental toxicology studies.

Induction of supernumerary ribs with sodium salicylate.

Although many chemical agents induce supernumerary ribs (SNR), few efforts have been published examining the induction of SNR in the presence or absence of maternal toxicity and the effect of dose on SNR length. A single administration of sodium salicylate on Day 9 of pregnancy at different dose levels (120, 180, 240, and 300 mg/kg) was used to induce SNR in the thoracolumbar region. At 180, 240, and 300 mg/kg, body weight loss was observed for dams following the administration, associated with reduced food consumption. The mean litter incidence of SNR in the control groups ranged between 0 and 17.1% and in the treated groups (from 180 to 300 mg/kg) between 50.5 and 88.6%. At 120 mg/kg, no adverse effects were noted in dams and the incidence of SNR was in the range of the control groups. Furthermore, in the three highest dose groups, increased incidences of 27 presacral vertebrae (PSV) were noted. In most instances, fetuses with 27 PSV had extra ribs whereas fetuses with 26 PSV tended to have rudimentary ribs. The distinction of SNR between rudimentary and extra ribs is usually based on a ratio of the length of 14th to 13th rib of 0.50. However, this value does not reflect the separation of the apparent bimodal distribution of SNR induced by sodium salicylate. A ratio of 0.35, which corresponds to the superior limit of the SNR of control fetuses, seemed to better define the two populations of SNR.

A two-generation reproduction study with hydroquinone in rats.

The effects of hydroquinone (HQ) on reproductive performance and fertility were assessed in a two-generation study with CD Sprague-Dawley rats (one litter per generation). HQ was administered in an aqueous solution by gavage at doses of 0, 15, 50, and 150 mg/kg/day. F0 and F1 parental animals were dosed daily for at least 10 weeks prior to cohabitation, during cohabitation, and until scheduled termination. At all dose levels tested, no adverse effects were observed on feed consumption, survival, or reproductive parameters for the F0 or F1 parental animals. Mild, transient tremors were observed shortly after dosing at 150 mg/kg/day in several F0 and F1 parental animals and in a single F0 male at 50 mg/kg/day. These tremors occurred infrequently and were considered to be due to an acute stimulatory effect of HQ on the nervous system. Body weights for F0 and F1 parental females were similar between all dose groups throughout the study. Body weights for F0 parental males were also comparable to those of control throughout the study. Statistically significant differences in body weights were noted for the F1 parental males in the 50 and 150 mg/kg/day dose groups at several intervals during the premating, mating, and postmating periods. No treatment-related effects on pup weight, sex distribution, or survival were noted for pups of either generation. Upon postmortem examination, no treatment-related gross lesions were observed in either the F0 or F1 parental animals or their weanlings. Histopathologic examination of reproductive tissues and pituitary glands from high-dose F0 and F1 parental animals did not reveal any changes related to treatment with HQ.(ABSTRACT TRUNCATED AT 250 WORDS)

A study of developmental toxicity of hydroquinone in the rabbit.

To obtain information on potential developmental toxicity, hydroquinone (HQ) was administered to pregnant New Zealand White rabbits (18 mated per dose group) in aqueous solution (0, 25, 75, or 150 mg HQ/kg/day) by gavage on Gestation Days (GD) 6 to 18. Caesarean sections were performed on GD 30. Doses of 75 and 150 mg/kg/day adversely affected feed consumption and/or body weights of dams during the treatment period. At these doses, however, treatment-related effects were not evident from physical observations, liver and kidney weights, premature delivery incidence, and caesarean sectioning data. The NOEL for maternal toxicity was 25 mg/kg/day. In the 150 mg/kg/day dose group, total incidences of external, visceral, and skeletal findings for fetuses did not differ statistically from controls. Slight, statistically insignificant, increases were found, however, in the incidences of ocular and minor skeletal malformations (micro-ophthalmia, vertebral/rib defects, angulated hyoid arch) on both a per fetus and a per litter basis. Under the conditions of this study, HQ at 150 mg/kg/day produced minimal developmental alterations in the presence of maternal toxicity. The NOEL for developmental toxicity was 75 mg/kg/day.

Hydroquinone: a developmental toxicity study in rats.

To determine the potential developmental toxicity of hydroquinone (HQ), pregnant rats (COBS-CD-BR) were given 0, 30, 100, or 300 mg/kg HQ by gavage on the 6th through the 15th days of gestation. Maternal effects included a slight, but significant (p less than or equal to 0.05), reduction in body weight gain and feed consumption for the 300 mg/kg HQ dams. Reproductive indices, i.e., pregnancy rate, numbers of corpora lutea, implantation sites, viable fetuses, and early and late resorptions, fetal sex ratio, pre- and postimplantation losses, and gravid uterine weights, were not affected by treatment with HQ. A slightly reduced (p less than or equal to 0.05) mean fetal body weight seen at the 300 mg/kg dose level was associated with the slightly reduced body weight gain seen for the dams at this dose level. Gross external, internal soft tissue, and skeletal examinations of the fetuses revealed no HQ-related malformations. The incidences of gross external variations (small hematomas) and internal soft tissue variations (dilated renal pelvis, hydronephrosis, and hydroureter) in the HQ-treated litters were not statistically different from the control incidences. Skeletal variations (delayed ossification of membranous skull bones, hyoid bone, thoracic centra 1-3, sacral arches 3 and 4, and bilobed thoracic centra 9-13) were seen with similar frequency in the control and HQ-treated groups. A statistically significant increase in the incidence of total common vertebral variations seen at the 300 mg/kg HQ dose level was not considered toxicologically significant. The incidences of total skeletal variations were not statistically different between the control and the HQ-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Worker exposure and protective clothing performance during manual seed treatment with lindane.

Twelve workers were monitored for exposure to 18.75% lindane dust formulation during manual wheat seed treatment. The mean total actual exposure rate was 32.89 mg/hr. Potential respiratory exposure averaged 0.0057 mg/hr (less than 1% of the total), with seven workers receiving no measurable respiratory exposures. Mean hand exposure was 1.84 mg/hr (5.6%). Dermal exposure to the head and neck averaged 4.28 mg/hr (13%). Exposure measured beneath the workshirt and workpants averaged 26.8 mg/hr (81.4%). The workshirt and workpants provided 3.4-fold and 11.5-fold protection factors, respectively. Forearm exposure measured beneath the workshirt represented more than 40% of total actual exposure. The small contribution of hand exposure to total dermal exposure was consistent with the use of chemical-resistant gloves by all workers. Total dermal exposure could be reduced substantially by wearing coveralls over regular work clothing, and by the use of guantlet-type gloves. It is recommended that worker education concerning personal hygiene and the appropriate use of protection clothing be made essential components of exposure reduction programs.