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PubMed1987

Two years of intrauterine contraception with levonorgestrel and with copper: a randomized comparison of the TCu 380Ag and levonorgestrel 20 mcg/day devices.

IUDs releasing 20 mcg/day of levonorgestrel (LNg20) were in randomized trial together with the Copper T, model TCu 380Ag, in seven centers involving 2244 women. Two-year (25 months) gross cumulative pregnancy rates were 0.2 +/- 0.2 and 0.9 +/- 0.3 for the levonorgestrel and copper releasing devices, respectively (P greater than 0.05). There were no ectopic pregnancies in more than 1600 woman-years of use of each device. Removal rates for bleeding and/or pain or for medical reasons other than menstrual problems did not differ significantly between devices. Oligomenorrhea or amenorrhea prompted 10.7 per hundred (gross rate, 8.4 net rate) women using the LNg 20 IUD to request removal in the two-year period, significantly above the 0.2 per hundred rate among women with the Copper IUD (P less than 0.001). At the end of two years an estimated 59.4 per 100 women were continuing use of the LNg 20 IUD, and 67.5 per 100 (P less than 0.001) with the TCu 380Ag. This difference is almost wholly ascribable to a marked reduction in bleeding episodes and days among women using the LNg 20 device with concomitant removal of device. Hemoglobin rose an average of 0.5 g/dl (P less than 0.001) for this group whereas women using the TCu 380Ag experienced a decline of 0.2 g/dl compared with baseline values (P less than 0.001).

Adolescent↗
PubMed1995

Breech delivery and foetal outcome: a review of 291 cases.

In a three year period (September 1989 to August 1992), among 7,170 consecutive deliveries at Yekatit 12 Hospital, Addis Abeba, Ethiopia, there were 291 singleton breech deliveries with a 4% incidence rate at a gestational age of 28 weeks and above. In 28% and 57% of the infants, weight was below 2,500 grams and Apgar score was less than 7 in the first minute, respectively. The gross perinatal mortality rate for breech delivery in the first 24 hours was 330 per 1,000 deliveries, which was significantly higher than for the total number of deliveries (70 per 1,000; p < 0.001). However, the perinatal mortality rate was 1,000 per 1,000 deliveries for foetuses of less than 1,500 grams, 635 for foetuses between 1,500-2,500 grams, and 156 for foetuses of greater than 2,500 gm. In general, foetuses with low birth weight showed a high mortality rate (p < 0.001). There was also a two-fold increase in perinatal death in patients without antenatal care (p < 0.001). In order to reduce this unacceptably high perinatal mortality, emphasis must be given to appropriate training of physicians and midwives in the management of breech deliveries along with provisions of efficient prenatal care to improve birth weight. In addition, as most of the neonatal problems are preventable, measures need to be taken to establish neonatal units equipped with basic resuscitation materials and manpower.

Adult↗
PubMedDate not supplied

Puerperal morbidity: a neglected area of maternal health in Sri Lanka.

Pregnancy is the period during which a mother prepares herself physically and psychologically for the delivery and care of the offspring. However, during this period the central concern is the welfare of the baby, but not the mother. When the mother and the child subsequently become two separate beings, the mother's health care is totally neglected unless she develops obvious symptoms of gross physiological and psychological abnormalities. This study, which was carried out in three MOH areas of the Kalutara District on maternal morbidity, had two main objectives. The first was to determine the prevalence of puerperal morbidity and the second was to identify characteristics of those with high levels of morbidity. Of the mothers who are registered by the PHM of the study area 600 were selected for this study. Data were collected using structured interviews conducted within the first week after puerperium (43-50 days after delivery). The morbidity rate revealed by the study is much higher than expected. Excessive bleeding from the vagina was reported by 40 per cent of mothers, while minor symptoms like breast engorgement and chills were reported by many mothers. Only 11 per cent of the mothers in the study did not have any symptoms or signs of ill health, and the rest reported one or more illnesses. Primae gravidae and those who experienced pregnancy wastage during an early pregnancy had a higher morbidity.

Adult↗
PubMed1983

Three-year experience with NORPLANT subdermal contraception.

NORPLANTTM (Laboratorios Gutfol, S.A., Mexico City, Mexico) subdermal implants containing levonorgestrel were accepted by 816 women in a two-phase study initiated in 1975 and augmented in 1978. Through 3 years of first-segment use, acceptors experienced five pregnancies, a cumulative net rate of 0.7 per 100, and a gross pregnancy rate of 1.1 per 100. First-segment continuation at 3 years was at the rate of 44.6 per 100, an annual average of 76 per 100. NORPLANT users experienced irregular menstruation, with high interindividual variation, but with normal average numbers of bleeding days and of bleeding episodes. Hemoglobin levels increased moderately during implant use. The incidence of systolic blood pressure readings above 145 mm Hg or diastolic readings above 95 mm Hg was similar to that observed among users of the TCu 200 intrauterine device enrolled under the same selection criteria in the same clinics between the two phases of the NORPLANT study. Comparative data on pregnancy and other rates are also given for these intrauterine device acceptors.

Adolescent↗
PubMed1991

The effect of adding copper onto Lippes Loop IUDs: results from a ten-year study in Yugoslavia.

The present study is the first randomized ten-year comparison of the standard, non-medicated Lippes Loop D and the same device with the addition of 200 mm2 of copper in the form of copper sleeves. The devices were randomly inserted immediately after first trimester medical termination of pregnancy. Out of 400 postabortal IUD insertions, 371 were followed for up to ten years. Gross cumulative life-table accidental pregnancy rates after one year of use were 0.56 for the copper-bearing Lippes Loop and 4.63 for the standard Lippes Loop. After two, four and ten years, these rates were 1.24, 2.70 and 3.62 and 6.03, 7.58 and 14.94, respectively (in all comparisons, rates were significantly different at the 0.05 level or lower). At each time interval, expulsion/displacement rates were 4.49, 4.49, 5.23 and 6.32 for the copper-bearing Lippes Loop and 12.61, 13.29, 15.46 and 19.79 for the standard Lippes Loop (rates were significantly different at the 0.01 level or lower). Differences in removal rates for bleeding and/or pain were not significantly different at any of the follow-up intervals. The lower event rates for copper-bearing Lippes Loop D users indicates that the addition of copper to the Lippes Loop IUD may result in better long-term efficacy profiles for this device among postabortal women. The results also suggest that large, medicated IUDs may be more efficacious for women with larger uteri who often experience higher failure rates due to expulsion or displacement of smaller IUDs into the lower uterine segment.

Adolescent↗
PubMed1991

Animal models of opiate, cocaine, and cannabis use.

A traditional concern with drugs administered during pregnancy has been teratogenicity or the production of gross structural malformations. Beginning in the 1970s, it became increasingly evident that the issue of drug safety and risk assessment went far beyond structural defects. During the 1980s, the newly emerged research specialty of "developmental toxicology" came to encompass a wide range of adverse toxic outcomes that include not only birth defects but also neurobehavioral and other functional effects as well. Substances of use and abuse--the opiates, cocaine, and cannabis--have come to exemplify a diverse group of compounds that produce a broad spectrum of developmental outcomes. Unlike alcohol, neither the use of heroin nor methadone during pregnancy is associated with an increased risk of birth defects but both produce a neonatal abstinence syndrome that can persist for as long as 6 months; follow-up to preschool years suggests possible risk of attention deficit and problems of fine motor coordination. Methodologic weaknesses of opiate animal models, especially with respect of appropriate dosing schedules, have hampered meaningful extrapolation of these studies to human risk assessment. Given the renewed interest in methadone maintenance as an important therapeutic intervention to reduce exposure to the human immunodeficiency virus, better designed animal studies are needed urgently to assess developmental risk, but these must incorporate techniques that better model human pharmacokinetics. Animal models of early cocaine exposure, driven by human reports of serious risk to the fetus and newborn, have found reproductive hazard, risk of neurobehavioral effects as well as altered CNS function. Whereas animal studies need to explore routes of administration other than sc and ig, particularly the volatilized form of cocaine, to date it appears that the processes of somatic growth and morphogenesis in rodents are not as sensitive to cocaine as is the functional development of the CNS. Finally, animal studies of cannabis have taught us some major methodologic and interpretive lessons for the continuing development and refinement of animal models of drugs of abuse. Of particular importance is that poorly controlled experiments that do not adequately consider the confounding influences of maternal toxicity, both prenatally and postnatally, are likely to yield a high rate of false-positive results. This is well illustrated by those studies of cannabis that antedated the current concern for pair-feeding and surrogate fostering. Nearly all of the studies that failed to include nutritional and fostering controls found neurobehavioral effects that included changes in activity as well as impairments in learning and memory.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2005

International collaborative study of intracytoplasmic sperm injection-conceived, in vitro fertilization-conceived, and naturally conceived 5-year-old child outcomes: cognitive and motor assessments.

OBJECTIVE: To date, very few studies have been conducted on the neurodevelopmental well-being of children conceived through intracytoplasmic sperm injection (ICSI). The limitations of these studies often include a lack of comparison with a demographically matched, naturally conceived (NC) group and the investigation of only very young children, with relatively small samples sizes. One study showed that there were no differences in IQ scores among ICSI-conceived, in vitro fertilization (IVF)-conceived, and NC children at 5 years of age. Unfortunately, psychomotor development was not assessed in that study. Because findings regarding these children's cognitive and motor development are inconclusive, the aim of this study was to shed more light on the cognitive and motor development of 5-year-old ICSI-conceived children. METHODS: A total of 511 ICSI-conceived children were compared with 424 IVF-conceived children and 488 NC controls. Children were recruited in 5 European countries, ie, Belgium, Denmark, Greece, Sweden, and the United Kingdom. Participation rates ranged from 45% to 96% in the ICSI and IVF groups and from 34% to 78% in the NC group. Cognitive and motor development was assessed with the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) and McCarthy Scales of Children's Abilities (MSCA) Motor Scale, respectively. The WPPSI-R consists of 2 major scales, ie, Verbal and Performance, each including 6 subtests. The 6 Performance Scale subtests are object assembly, geometric design, block design, mazes, picture completion, and animal pegs. The 6 Verbal Scale subtests are information, comprehension, arithmetic, vocabulary, similarities, and sentences. Scores on the Performance and Verbal Scale subtests are summed to yield the performance IQ (PIQ) and verbal IQ (VIQ), respectively. Scores on both the Performance Scale and the Verbal Scale yield the full-scale IQ (FSIQ). IQ scales have a mean score of 100 and a SD of 15. Each subtest has a mean score of 10 and a SD of 3. The MSCA consists of 6 scales, ie, Verbal, Perceptual-Performance, Quantitative, General Cognitive, Memory, and Motor Scale. In this study, only the Motor Scale was administered. This scale assesses the child's coordination during performance of a variety of gross- and fine-motor tasks. Leg coordination, arm coordination, and imitative action tests provide measures of gross-motor ability. Draw-a-design and draw-a-child assess fine-motor coordination, as revealed by the levels of hand coordination and finger dexterity. The mean score for this test is 50, with a SD of . RESULTS: No differences were identified among ICSI, IVF, and NC children with respect to VIQ, PIQ, or FSIQ scores of the WPPSI-R. Furthermore, there were no differences between groups regarding the discrepancy between VIQ and PIQ scores. These results were not influenced by gender, country, or maternal educational level. However, in the subgroup of firstborn children with mothers who gave birth at an older age (33-45 years), NC children obtained significantly better VIQ and FSIQ scores than did children conceived through assisted reproductive technologies. These differences in VIQ and FSIQ scores between ICSI/IVF and NC children were relative, because NC children scored <1 IQ point higher than ICSI/IVF children. Therefore, these scores show no clinical relevance. For Verbal Scale subtests, variables such as age of the mother at the time of the birth, educational level of the mother, and gender and nationality of the child interacted with mode of conception, resulting in clinically irrelevant differences between scores for the ICSI/IVF and NC groups on the arithmetic, vocabulary, and comprehension subtests. For Performance Scale subtests, these same demographic factors interacted with mode of conception for the block design, object assembly, and animal pegs subtests, again resulting in clinically irrelevant differences among groups. In the 3 groups (ICSI, IVF, and NC), we observed equal numbers of children scoring below 1 SD from the mean on the WPPSI-R and the MSCA. CONCLUSIONS: This study includes a substantial number of children from several European countries. Apart from a few interaction effects between mode of conception and demographic variables, no differences were found when ICSI, IVF, and NC scores on the WPPSI-R and MSCA Motor Scale were compared. Nevertheless, the aforementioned interaction effects could indicate that demographic variables such as maternal age at the time of the birth and maternal educational level play different roles in the cognitive development of IVF and ICSI children, compared with NC children. Additional research is needed to explore and verify this finding. Previous studies revealed that ICSI children, in comparison with NC children, more frequently obtained scores below 1 SD from the mean on 3 subtests of the Performance Scale (object assembly, block design, and mazes) or showed a trend of 5.2% of ICSI children, compared with 2.5% of IVF children and 0.9% of NC children, obtaining a score below 1 SD from the mean, but those findings were not confirmed in this study. Here no differences were found among the 3 groups in the numbers of children scoring below 1 SD from the mean on the VIQ, PIQ, and FSIQ tests and the Verbal and Performance Scale subtests. Motor development results were somewhat more conclusive. There were no differences between the scores of ICSI, IVF, and NC children on the MCSA Motor Scale. No interaction effects were found between mode of conception and demographic variables, indicating that these results are not influenced by gender, nationality, maternal educational level, or maternal age at the time of the birth. Furthermore, equal proportions of children in all 3 groups scored below 1 SD from the mean. The results of this study are reassuring for parents who conceived through ICSI (or IVF). The findings indicate that the motor and cognitive development of their offspring is very similar to that of NC children. However, demographic factors such as maternal educational level and maternal age at the time of the birth might play different roles in the cognitive development of ICSI and IVF children, compared with NC children.

Case-Control Studies↗
PubMed2005

Male-mediated developmental toxicity in mice after 8 weeks'exposure to low doses of X-rays.

PURPOSE: The aim of the study was to investigate the effects of subchronic irradiation of male mice on reproduction ability and induction of male-mediated teratogenesis. MATERIALS AND METHODS: Male mice were irradiated to 0.05 Gy, 0.10 Gy and 0.20 Gy daily for 8 weeks, 5 days per week. The total doses were 2.00 Gy, 4.00 Gy and 8.00 Gy, respectively. After the end of exposure each male was caged with two untreated females. The females were sacrificed on day 17 based on the finding of a vaginal plug. Females were examined for the number of live and dead implantations and the incidence of congenital malformations of survival foetuses. RESULTS: The fertilization ability of males was not diminished. The exposure to 0.20 Gy daily significantly decreased the percent of pregnant females and the number of total implantations. Exposure to 0.10 Gy and 0.20 Gy daily caused decreases in the number of live foetuses and induced dominant lethal mutations (over 50% at the highest dose). Exposure to each dose significantly enhanced the number of deaths (especially early) implants. The incidence of gross and skeletal malformations was not statistically significant, except for skeletal malformations at the highest dose. CONCLUSIONS: Results confirmed that irradiation of male germ cells cause genetic effects which could be transmitted to the offspring. After subchronic exposure to low doses the majority of mutations caused premature death. Subchronic exposure to low doses of X-rays did not induce external and skeletal malformations of surviving foetuses.

Abnormalities, Radiation-Induced↗
PubMed1995

Use of performance ratios to calculate the economic impact of thin cows in a beef cattle herd.

OBJECTIVE: To determine gross income lost that was attributable to thin cows in a beef cattle herd, to estimate the cost of added nutrition necessary to prevent thin cows in the herd, and to determine the financial outcome of the improved nutritional practices. DESIGN: Prospective, observational study. ANIMALS: Four hundred and twenty-two Santa Gertrudis cows and their calves. PROCEDURE: At pregnancy examination in the fall of 1992, cows were assigned a body condition score (BCS), using a scale of 1 (emaciated) to 9 (obese), and the ratio of the productivity of BCS-3 and BCS-4 cow groups (thin cows), compared with the mean productivity of BCS-5 and BCS-6 cows (cows in good condition), was determined. Measures of productivity evaluated included pregnancy rates, weaning weights, and prices per hundredweight of calves. The performance ratios of BCS-3 and BCS-4 cows were multiplied by the mean gross income of BCS-5 and BCS-6 cows to calculate their gross income. This was then subtracted from the mean income of BCS-5 and BCS-6 cows to estimate the amount of lost gross income per thin cow. The cost of a nutritional program that would prevent thin cows in the herd was subtracted from the lost gross income of the thin cows to yield the amount of increased net income that could be generated from a nutritional program that would maintain cows in the herd at a BCS of 5 or 6. RESULTS: Cows with a BCS of 3 were 0.48 as productive, and cows with a BCS of 4 were 0.74 as productive as the average of the BCS-5 and BCS-6 cows combined. Each BCS-3 cow generated $215.06 less, and each BCS-4 cow generated $107.53 less gross income than the average gross income of BCS-5 and BCS-6 cows. The added cost of nutrition that would have reconditioned BCS-3 and BCS-4 cows to a BCS of 5.5 was $91.48/BCS-3 cow and $43.67/BCS-4 cow. Implementation of the reconditioning nutrition program the previous fall would have resulted in an extra net income of $123.58/BCS-3 cow and $63.86/BCS-4 cow, received over a 2-year period. The 262 thin cows in the herd accounted for a total net income loss of $19,897. CLINICAL IMPLICATIONS: The time of pregnancy examination is a strategic intervention point to estimate the past negative economic impact of thin cows and to implement a plan to prevent these losses in the future. Pregnancy examinations should be performed at least 100 days before the beginning of the calving season, and thin pregnant cows should be sorted into a special group and fed a reconditioning diet that will improve their body condition to an average BCS of 5.5 by the onset of the calving season.

Animal Husbandry↗
PubMed2005

Environmental contaminants and biomarker responses in fish from the Rio Grande and its U.S. tributaries: spatial and temporal trends.

We collected, examined, and analyzed 368 fish of seven species from 10 sites on rivers of the Rio Grande Basin (RGB) during late 1997 and early 1998 to document temporal and geographic trends in the concentrations of accumulative contaminants and to assess contaminant effects on the fish. Sites were located on the mainstem of the Rio Grande and on the Arroyo Colorado and Pecos River in Texas (TX), New Mexico (NM), and Colorado. Common carp (Cyprinus carpio) and largemouth bass (Micropterus salmoides) were the targeted species. Fish were examined in the field for internal and external visible gross lesions, selected organs were weighed to compute ponderal and organosomatic indices, and samples of tissues and fluids were obtained and preserved for analysis of fish health and reproductive biomarkers. Whole fish from each station were composited by species and gender and analyzed for organochlorine chemical residues and elemental contaminants using instrumental methods, and for 2,3,7,8-tetrachloro dibenzo-p-dioxin-like activity (TCDD-EQ) using the H4IIE rat hepatoma cell bioassay. Overall, fish from lower RGB stations contained greater concentrations of organochlorine pesticide residues and appeared to be less healthy than those from sites in the central and upper parts of the basin, as indicated by a general gradient of residue concentrations and biomarker responses. A minimal number of altered biomarkers and few or no elevated contaminant concentrations were noted in fish from the upper RGB. The exception was elevated concentrations [up to 0.46 microg/g wet-weight (ww)] of total mercury (Hg) in predatory species from the Rio Grande at Elephant Butte Reservoir, NM, a condition documented in previous studies. Arsenic (As) and selenium (Se) concentrations were greatest in fish from sites in the central RGB; Se concentrations in fish from the Pecos River at Red Bluff Lake, TX and from the Rio Grande at Langtry, TX and Amistad International Reservoir, TX exceeded published fish and wildlife toxicity thresholds. In the lower RGB, residues of p,p'-DDT metabolites (<or=1.69 microg/g ww), chlordane-related compounds (<or=0.21 microg/g ww), dieldrin (<or=0.0.05 microg/g ww), and toxaphene (<or=2.4 microg/g ww) were detected in fish from most sites; maximum concentrations were in channel catfish (Ictalurus punctatus) from the Arroyo Colorado at Harlingen, TX. Concentrations of one or more residues exceeded toxicity thresholds for fish and wildlife in fish from this site and from the Rio Grande at Mission, TX and Brownsville, TX; however, concentrations were lower than those reported by previous studies. In addition, the proportional concentrations of p,p'-DDT at all sites were low, indicating weathered DDT rather than the influx of new material. Concentrations of total PCBs (<0.05 microg/g ww) and TCDD-EQ (<or=6 pg/g ww) were comparatively low in all samples. Hepatic ethoxyresorufin O-deethylase (EROD) activity in some fish was elevated relative to reference rates at most sites, but was generally lower than previously reported activity in fish from heavily contaminated locations. The comparatively low PCB and TCDD-EQ concentrations together with elevated EROD activity may reflect exposure to polycyclic aromatic hydrocarbons. Reproductive biomarkers were consistent with chronic contaminant exposure at lower RGB sites; comparatively large percentages of intersex male largemouth bass, relatively low gonadosomatic indices, and elevated plasma vitellogenin concentrations in male fish were noted at three of the four stations. Large percentages of atretic eggs were also observed in the ovaries of female common carp from the Rio Grande at Brownsville, TX. Although many of the conditions noted may have other causes in addition to contaminant exposure, the biomarker results for the lower RGB sites are consistent with subtle responses of fish to contaminants, an interpretation supported by the chemical data of this and other investigations.

Animals↗
PubMed2005

Final report of the safety assessment of L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate as used in cosmetics.

L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate function in cosmetic formulations primarily as antioxidants. Ascorbic Acid is commonly called Vitamin C. Ascorbic Acid is used as an antioxidant and pH adjuster in a large variety of cosmetic formulations, over 3/4 of which were hair dyes and colors at concentrations between 0.3% and 0.6%. For other uses, the reported concentrations were either very low (<0.01%) or in the 5% to 10% range. Calcium Ascorbate and Magnesium Ascorbate are described as antioxidants and skin conditioning agents--miscellaneous for use in cosmetics, but are not currently used. Sodium Ascorbyl Phosphate functions as an antioxidant in cosmetic products and is used at concentrations ranging from 0.01% to 3%. Magnesium Ascorbyl Phosphate functions as an antioxidant in cosmetics and was reported being used at concentrations from 0.001% to 3%. Sodium Ascorbate also functions as an antioxidant in cosmetics at concentrations from 0.0003% to 0.3%. Related ingredients (Ascorbyl Palmitate, Ascorbyl Dipalmitate, Ascorbyl Stearate, Erythorbic Acid, and Sodium Erythorbate) have been previously reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel and found "to be safe for use as cosmetic ingredients in the present practices of good use." Ascorbic Acid is a generally recognized as safe (GRAS) substance for use as a chemical preservative in foods and as a nutrient and/or dietary supplement. Calcium Ascorbate and Sodium Ascorbate are listed as GRAS substances for use as chemical preservatives. L-Ascorbic Acid is readily and reversibly oxidized to L-dehydroascorbic acid and both forms exist in equilibrium in the body. Permeation rates of Ascorbic Acid through whole and stripped mouse skin were 3.43 +/- 0.74 microg/cm(2)/h and 33.2 +/- 5.2 microg/cm(2)/h. Acute oral and parenteral studies in mice, rats, rabbits, guinea pigs, dogs, and cats demonstrated little toxicity. Ascorbic Acid and Sodium Ascorbate acted as a nitrosation inhibitor in several food and cosmetic product studies. No compound-related clinical signs or gross or microscopic pathological effects were observed in either mice, rats, or guinea pigs in short-term studies. Male guinea pigs fed a control basal diet and given up to 250 mg Ascorbic Acid orally for 20 weeks had similar hemoglobin, blood glucose, serum iron, liver iron, and liver glycogen levels compared to control values. Male and female F344/N rats and B6C3F(1) mice were fed diets containing up to 100,000 ppm Ascorbic Acid for 13 weeks with little toxicity. Chronic Ascorbic Acid feeding studies showed toxic effects at dosages above 25 mg/kg body weight (bw) in rats and guinea pigs. Groups of male and female rats given daily doses up to 2000 mg/kg bw Ascorbic Acid for 2 years had no macro- or microscopically detectable toxic lesions. Mice given Ascorbic Acid subcutaneous and intravenous daily doses (500 to 1000 mg/kg bw) for 7 days had no changes in appetite, weight gain, and general behavior; and histological examination of various organs showed no changes. Ascorbic Acid was a photoprotectant when applied to mice and pig skin before exposure to ultraviolet (UV) radiation. The inhibition of UV-induced suppression of contact hypersensitivity was also noted. Magnesium Ascorbyl Phosphate administration immediately after exposure in hairless mice significantly delayed skin tumor formation and hyperplasia induced by chronic exposure to UV radiation. Pregnant mice and rats were given daily oral doses of Ascorbic Acid up to 1000 mg/kg bw with no indications of adult-toxic, teratogenic, or fetotoxic effects. Ascorbic Acid and Sodium Ascorbate were not genotoxic in several bacterial and mammalian test systems, consistent with the antioxidant properties of these chemicals. In the presence of certain enzyme systems or metal ions, evidence of genotoxicity was seen. The National Toxicology Program (NTP) conducted a 2-year oral carcinogenesis bioassay of Ascorbic Acid (25,000 and 50,000 ppm) in F344/N rats and B6C3F(1) mice. Ascorbic Acid was not carcinogenic in either sex of both rats and mice. Inhibition of carcinogenesis and tumor growth related to Ascorbic Acid's antioxidant properties has been reported. Sodium Ascorbate has been shown to promote the development of urinary carcinomas in two-stage carcinogenesis studies. Dermal application of Ascorbic Acid to patients with radiation dermatitis and burn victims had no adverse effects. Ascorbic Acid was a photoprotectant in clinical human UV studies at doses well above the minimal erythema dose (MED). An opaque cream containing 5% Ascorbic Acid did not induce dermal sensitization in 103 human subjects. A product containing 10% Ascorbic Acid was nonirritant in a 4-day minicumulative patch assay on human skin and a facial treatment containing 10% Ascorbic Acid was not a contact sensitizer in a maximization assay on 26 humans. Because of the structural and functional similarities of these ingredients, the Panel believes that the data on one ingredient can be extrapolated to all of them. The Expert Panel attributed the finding that Ascorbic Acid was genotoxic in these few assay systems due to the presence of other chemicals, e.g., metals, or certain enzyme systems, which effectively convert Ascorbic Acid's antioxidant action to that of a pro-oxidant. When Ascorbic Acid acts as an antioxidant, the Panel concluded that Ascorbic Acid is not genotoxic. Supporting this view were the carcinogenicity studies conducted by the NTP, which demonstrated no evidence of carcinogenicity. Ascorbic Acid was found to effectively inhibit nitrosamine yield in several test systems. The Panel did review studies in which Sodium Ascorbate acted as a tumor promoter in animals. These results were considered to be related to the concentration of sodium ions and the pH of urine in the test animals. Similar effects were seen with sodium bicarbonate. Because of the concern that certain metal ions may combine with these ingredients to produce pro-oxidant activity, the Panel cautioned formulators to be certain that these ingredients are acting as antioxidants in cosmetic formulations. The Panel believed that the clinical experience in which Ascorbic Acid was used on damaged skin with no adverse effects and the repeat-insult patch test (RIPT) using 5% Ascorbic Acid with negative results supports the finding that this group of ingredients does not present a risk of skin sensitization. These data coupled with an absence of reports in the clinical literature of Ascorbic Acid sensitization strongly support the safety of these ingredients.

Administration, Oral↗