Developmental Toxicity Study of Orally Administered Lithium Hypochlorite in Rats

1990 ◽  
Vol 9 (3) ◽  
pp. 367-379 ◽  
Author(s):  
Alan M. Hoberman ◽  
John R. Deprospo ◽  
Elizabeth A. Lochry ◽  
Mildred S. Christian
Keyword(s):  
Body Weight ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Deionized Water ◽  
Feed Consumption ◽  
Corpora Lutea ◽  
Test Substance ◽  
Thoracic Vertebrae ◽  
Chlorine Toxicity ◽  
Metacarpal Bones

The purpose of this study was to examine the developmental toxicity of lithium hypochlorite in Sprague-Dawley rats. Groups of 25 pregnant rats received lithium hypochlorite at dosages of 0 (vehicle-reverse osmosis deionized water), 10, 50, 100, or 500 mg/kg/day, via oral gavage once daily on days 6 through 15 of gestation. The test solution was not adjusted for ion concentration. All dosages were given at a volume of 10 m/kg per day, adjusted daily for body weight. The rats were given RO deionized water for drinking, to prevent ingestation of chlorine or any other ions except those provided by the test substance. Clinical signs, body weight, and feed consumption were recorded daily during the dosage and postdosage periods. Caesarean-sectioning of the rats occurred on day 20 of gestation. Evaluations were made for pregnancy, number and placement of implantations, early and late resorptions, fetal viability, and number of corpora lutea. Fetuses were subsequently examined for gender, body weight, and gross external, soft tissue, and skeletal alterations. Significant (p ≤ 0.05 to p ≤ 0.01) maternal toxicity was observed in the 500 mg/kg per day dosage group, which included maternal death, clinical signs, gross necropsy findings, and inhibited maternal body weight gain and feed consumption. These effects were consistent with those expected from chlorine toxicity. The only effects of this dosage on embryo-fetal development were small reversible delays in growth (decreased fetal body weight, wavy ribs and delayed ossification of the thoracic vertebrae (bifid centra), forepaw and hindpaw phalanges, and metatarsal and metacarpal bones). Average values for corpora lutea, implantation sites, litter sizes, live and dead fetuses, and resorptions were comparable in the five dosage groups andlor were within the range observed historically. On the basis of these data, both the maternal no-observable-adverse-effect level (NOAEL) and the developmental NOAEL for lithium hypochlorite were 100 mg/kg per day. These data are in agreement with other studies and demonstrate that developmental toxicity of lithium hypochlorite does not occur in the absence of overt maternal toxicity.

Evaluation of the Developmental Toxicity of Acetyl Cedrene

2006 ◽  
Vol 25 (5) ◽  
pp. 423-428 ◽  
Author(s):  
Aurelia Lapczynski ◽  
Daniel A. Isola ◽  
Mildred S. Christian ◽  
Robert M. Diener ◽  
Anne Marie Api
Keyword(s):  
Body Weight ◽  
Soft Tissue ◽  
Corn Oil ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Body Weights ◽  
Weight Gains

The developmental toxicity of acetyl cedrene (AC), a widely used fragrance ingredient, was evaluated in pregnant Sprague-Dawley rats (25/group). Gavaged dosages of 0 (corn oil), 25, 50, or 100 mg/kg/day were administered on days 7 through 17 of gestation (GDs 7 to 17). First and last day dosing suspensions were analyzed for AC content. All rats were observed daily for viability, clinical signs, abortions, and premature deliveries. Body weights were recorded at frequent intervals. Cesarean-sectioning and necropsy examinations were performed on GD 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. The number of corpora lutea in each ovary was also recorded. Fetuses were weighed and examined for gender and gross external changes and soft tissue or skeletal alterations. Totals of 25, 23, 21, and 24 rats became pregnant in the 0 (control), 25, 50 and 100 mg/kg/day groups, respectively, and analysis of dosage preparations verified that administered dosages reflected calculated dosages ±10%. No deaths or premature deliveries occurred in the study. Clinical signs included excessive salivation, which was attributed to the administration of AC. When compared to controls, significant reductions in feed consumption and body weight gains occurred only at 100 mg/kg/day. Both absolute (g/day) and relative (g/kg/day) feed consumption values were significantly decreased on GDs 7 to 12. Relative values were decreased significantly on GDs 15 to 18. Body weight gains were significantly reduced on GDs 7 to 10. Mean maternal body weights remained significantly lower than controls on GDs 9 to 14, but a marked compensatory increase in feed consumption on GDs 15 to 18 prevented further deterioration in body weight gains. No cesarean-sectioning or litter parameters were affected by dosages of AC and necropsy of the dams after cesarean section did not reveal any gross changes attributable to AC. No gross external, soft tissue, or skeletal fetal alterations (malformations or variations) were attributed by dosages AC. The average number of ossifications sites per fetus per litter did not differ among the groups. Based on these data, maternal and developmental no-observable-adverse-effect levels (NOAELs) of 50 and 100 mg/kg/day, respectively, were established for AC.

Evaluation of the Developmental Toxicity of Linalool in Rats

2008 ◽  
Vol 27 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Valerie T Politano ◽  
Elise M Lewis ◽  
Alan M Hoberman ◽  
Mildred S Christian ◽  
Robert M Diener ◽  
...  
Keyword(s):  
Body Weight ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Weight Gains ◽  
Adverse Effect Level ◽  
Effect Level

The developmental toxicity of linalool, a widely used fragrance ingredient, was evaluated in presumed pregnant Sprague-Dawley rats (25/group). Oral dosages of 0, 250, 500, or 1000 mg/kg/day linalool were administered by gavage on gestational days 7 to 17. The presence of spermatozoa and/or a copulatory plug in situ was designated as gestational day 0. Rats were observed for viability, clinical signs, body weights, and feed consumption. Caesarean sectioning and necropsy occurred on gestational day 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. Numbers of corpora lutea were also recorded. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. There were no maternal deaths, clinical signs, or gross lesions that were considered related to linalool. During the dosage period, mean relative feed consumption was significantly reduced by 7% and mean body weight gains were reduced by 11% at 1000 mg/kg/day. During the postdosage period, feed consumption values at 1000 mg/kg/day were significantly higher than vehicle control values, which corresponded to the increase in body weight gains during this period. Caesarean section and litter parameters, as well as fetal alterations, were not affected by linalool at any of the three dosages tested. On the basis of these data, the maternal no observed adverse effect level (NOAEL) of linalool is 500 mg/kg/day, whereas the developmental NOAEL is ≥ 1000 mg/kg/day. It is concluded that linalool is not a developmental toxicant in rats at maternal doses of up to 1000 mg/kg/day.

Developmental Toxicity Studies of Triethylene Glycol Monomethyl Ether Administered Orally to Rats and Rabbits

1996 ◽  
Vol 15 (5) ◽  
pp. 349-370 ◽  
Author(s):  
A. M. Hoberman ◽  
W. J. Krasavage ◽  
M. S. Christian ◽  
C. R. Stack
Keyword(s):  
Developmental Toxicity ◽  
Clinical Signs ◽  
Triethylene Glycol ◽  
Monomethyl Ether ◽  
Feed Consumption ◽  
Corpora Lutea ◽  
Maternal Body ◽  
Body Weights ◽  
Effect Level ◽  
Dose Levels

Triethylene glycol monomethyl ether (TGME) was administered orally via gavage stomach tube to mated Caesarean delivered (CD) rats and artificially inseminated New Zealand white rabbits on days 6–15 and 6–18 of gestation, respectively, at dose levels of 0, 625, 1,250, 2,500, or 5,000 mg/kg/day (rats) and 0, 250, 500, 1,000, or 1,500 mg/kg/day (rabbits). Clinical signs, maternal body weights, and feed consumption were monitored throughout the treatment period. The surviving rats and rabbits underwent Caesarean section on day 20 and day 29 of gestation, respectively. Fetuses were weighed, sexed, and examined externally and for soft tissue and skeletal alterations. In rats, the high dose significantly reduced maternal body weights, feed consumption, and gravid uterine weights. One dam in this group died on day 13 of gestation. Treatment-related clinical signs were seen only at the highest dose tested. Maternal feed consumption was significantly reduced at 5,000 and 2,500 mg/kg and slightly, but not significantly, reduced at 1,250 mg/kg. Doses as high as 5,000 mg/kg/day did not affect pregnancy rate, implantations, corpora lutea, live fetuses, or fetal sex ratios. Resorptions were significantly increased at 5,000 mg/kg, and fetal body weights were slightly reduced at 1,250 mg/kg and significantly reduced at 2,500 and 5,000 mg/kg. The incidences of malformations and external or internal soft tissue variations were not increased at doses as high as 5,000 mg/kg. Incidences of skeletal variations were increased at doses of 1,250 mg/kg and higher. The no-observable-effect level (NOEL) in rats, for both maternal and developmental toxicity, was 625 mg/kg, while 1,250 mg/kg was a no-observable-adverse-effect level (NOAEL) for maternal toxicity and may be very near the NOAEL for developmental toxicity. In rabbits, 1,500 mg/kg/day reduced maternal body weights and feed consumption and caused death, abortions, treatment-related clinical signs of toxicity, and reduced gravid uterine weights. One doe in the 1,000 mg/kg group died on day 18 of gestation, but no treatment-related signs were seen in the other animals in this group. Doses as high as 1,500 mg/kg did not significantly affect pregnancy rate, implantations, corpora lutea, resorptions, live fetuses, fetal body weights, or sex ratio. Incidences of malformations or external and internal variations were not increased at any of the dose levels. The only developmental toxicity seen in the rabbit was an increase in the incidence of two common skeletal variations, angulated hyoid alae and delayed ossification of the xiphoid process, at the highest dose tested. For maternal toxicity, the NOEL and NOAEL were 250 mg/kg and 500 mg/kg, respectively, and for developmental toxicity the NOEL and NOAEL were 1,000 mg/kg and 1,500 mg/kg, respectively. These studies indicate that TGME was not selectively toxic to developing rat or rabbit conceptuses.

Tamarind Seed Polysaccharide

2013 ◽  
Vol 32 (3) ◽  
pp. 198-208 ◽  
Author(s):  
James T. Heimbach ◽  
Hiroshi Egawa ◽  
Palma Ann Marone ◽  
Mark R. Bauter ◽  
Elke Kennepohl
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Consumption ◽  
Body Weight Gain ◽  
Clinical Chemistry ◽  
Clinical Signs ◽  
Female Rats ◽  
Feed Consumption ◽  
Test Substance ◽  
Tamarind Seed

Forty male and 40 female Crl:SD® CD® IGS rats were fed diets containing 0, 40 000, 80 000, or 120 000 ppm tamarind seed polysaccharide (equivalent to 3450.8, 6738.9, or 10 597.1 mg/kg bw/day and 3602.1, 7190.1, or 10 690.7 mg/kg bw/day for males and females, respectively) for 28 days. Animals were observed for adverse clinical signs, body weight, feed consumption, hematology and clinical chemistry parameters, urinalysis values were recorded, and at the end of the study the rats underwent a full necropsy. Functional Observational Battery (FOB) and Motor Activity (MA) tests were performed on all animals. There were no mortalities, no clinical or ophthalmologic signs, body weight, body weight gain, food consumption and food efficiency, FOB or MA findings associated with the administration of tamarind seed polysaccharide. Initial statistically significant decreases in body weight gain and food consumption resolved after the first week and were considered the result of reduced palatability. There were no adverse changes in hematology, coagulation, clinical chemistry or urinalysis parameters in male or female rats considered the result of test substance administration. At necropsy, there were no macroscopic, histopathological findings, estrus cycle, or organ weight changes deemed related to administration of the test substance. Under the conditions of this study and based on the toxicological endpoints evaluated, the no-observed-adverse-effect level (NOAEL) for tamarind seed polysaccharide in the diet was the highest concentration tested of 120 000 ppm (equivalent to 10 597 mg/kg bw/day and 10 691 mg/kg bw/day for male and female rats, respectively).

Studies of the Toxicological Potential of Capsinoids: IV. Teratology Studies of CH-19 Sweet Extract in Rats and Rabbits

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 41-57 ◽  
Author(s):  
Bruce K. Bernard ◽  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Body Weight ◽  
Sex Ratio ◽  
Food Consumption ◽  
Clinical Signs ◽  
Pathological Finding ◽  
High Dose ◽  
Corpora Lutea ◽  
Test Substance ◽  
Sprague Dawley ◽  
Adverse Effect Level

In order to evaluate the safety of CH-19 Sweet extract that contains capsinoids, teratology studies were conducted in pregnant Sprague-Dawley rats (20 rats per group) and pregnant New Zealand white rabbits (17 to 22 animals per group). The test substance was administered to rats by gavage for 11 days on gestation days 7 to 17 at doses of 0 (vehicle), 1.25, 2.5, and 5.0 ml/kg and to rabbits for 13 days on gestation days 6 to 18 at doses of 0 (vehicle), 0.25, 0.5, and 1.0 ml/kg. As the concentration of capsinoids in CH-19 Sweet extract was 72.2 to 75.05 mg/ml, the resulting dose of capsinoids administered to rats was 90.25, 180.5, and 361 mg/kg, and to rabbits was 18.76, 37.53, and 75.05 mg/kg in the vehicle, low-, mid-, and high-dose groups, respectively. In the rat study, no deaths occurred in any group and there were no test substance–related changes or abnormalities in clinical signs, body weight, food consumption, or gross pathological findings. There were no test substance–related changes in the number of corpora lutea, number or index of implantations, index of embryofetal deaths, number of live fetuses, sex ratio, fetal body weight at the end of the gestation period, or abnormalities in the placenta of live fetuses. There were no test substance–related abnormalities or variations in the external, skeletal, or visceral examinations of live fetuses. It was concluded that the test article caused neither teratogenic effects nor abnormalities in the progression of ossification. In the rabbit study, there were no test substance–related effects on clinical signs, body weight, food consumption, or necropsy findings. There were neither test substance–related abortions nor test substance–related effects on the number of corpora lutea, or number or index of implantations. There were no test substance–related effects on the number of dead embryos/fetuses, the number of live fetuses, sex ratio, body weight of live fetuses, or gross pathological finding in the placentas. There were no test substance–related external abnormalities or incidences of visceral or skeletal abnormalities or variations, and there were no test substance–related effects on the progress of ossification in any group. The authors concluded the no observed adverse effect level (NOAEL) of CH-19 Sweet extract containing capsinoids on pregnant animals and fetal development/growth was >5.0 ml/kg/day (>361 mg/kg/day as capsinoids) in rats and >1.0 ml/kg/day (>75.05 mg/kg/day as capsinoids) in rabbits.

Evaluation of the Developmental Toxicity of α-Methyl-3,4-Methylene-Dioxyhydrocinnamic Aldehyde in Rats

2006 ◽  
Vol 25 (2) ◽  
pp. 127-132 ◽  
Author(s):  
Anne Marie Api ◽  
Elise M. Lewis ◽  
Alan M. Hoberman ◽  
Mildred S. Christian ◽  
Robert M. Diener
Keyword(s):  
Corn Oil ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Pregnant Rats ◽  
Excessive Salivation ◽  
Sprague Dawley Rats ◽  
Body Weights

The developmental toxicity of α-methyl-3,4-methylene-dioxyhydrocinnamic aldehyde (MMDHCA), a widely used fragrance ingredient, was evaluated for developmental toxicity in Sprague-Dawley rats (25/group; cesarean-sectioning identified 21 to 25 pregnant rats/group). Oral dosages of 0 (corn oil), 62, 125, or 250 mg/kg/day were administered by gavage on days 7 through 17 of gestation (GDs 7 through 17). Rats were observed for viability, clinical signs, body weights, and feed consumption. Necropsy and cesarean sectioning occurred on GD 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. Numbers of corpora lutea were also recorded. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. Analysis of dosage preparations verified calculated dosages ±10%. No deaths occurred. Excessive salivation occurred in all groups, but the incidence was increased at 250 mg/kg/day. The 250 mg/kg/day dosage also was associated with a significant increase in the incidences of a clear, red or yellow perioral and/or red perivaginal substance and significant reductions in mean feed consumption and body weight gains (11.6% and 7.4%, respectively) during the entire dosage period. No gross changes attributable to MMDHCA were observed at necropsy. Cesarean section or litter parameters, as well as fetal alterations, were not affected by MMDHCA at 250 mg/kg/day or either of the lower dosages tested. Based on these data, maternal and developmental no-observable-effect levels (NOAELs) of 125 and >250 mg/kg/day, respectively, were established for MMDHCA. It is concluded that MMDHCA is not a developmental toxicant in rats under the conditions of this study and dosing regimen.

scholarly journals Developmental Toxicity of Levo-Alpha-Acetylmethadol (LAAM) in Tolerant Rats

2002 ◽  
Vol 21 (2) ◽  
pp. 147-159 ◽  
Author(s):  
Raymond G. York ◽  
Kevin H. Denny ◽  
David E. Moody ◽  
Mario E. Alburges
Keyword(s):  
Body Weight ◽  
Body Weight Gain ◽  
Fetal Liver ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Fetal Brain ◽  
Female Rats ◽  
Feed Consumption ◽  
Fetal Plasma ◽  
Range Finding

Mated Crl:CD VAF/Plus female rats, in a range-finding study ( n = 5–6 per dose) and a subsequent definitive study ( n = 30 per dose) were used to determine the developmental toxicity, including the teratogenic potential of levo-alpha-acetyhnethadol (LAAM) hydrochloride, in tolerant rats. Tolerance was induced by initially administering the drug by gavage (10 ml/kg) at 2 mg/kg/day and increasing the dose every 2 weeks for 12 weeks until the doses of 2, 6, 9, 12, and 15, or 2, 6, and 12 mg/kg/day were achieved in the range-finding or definitive study, respectively. Females were then mated to stock males and treated throughout mating and gestation. Controls received distilled water on a similar regimen. The range-finding experiment was used for initial clinical evaluations and to determine tissue concentrations of LAAM and metabolites. In plasma, liver, and brain collected from dams and fetuses pooled by litter on gestation day 20, LAAM and its two N-demethylated metabolites, norLAAM and dinorLAAM, showed dose-dependent increases in concentration and in tissue to plasma ratios. Tissue to dam plasma ratios were highest in dam liver (17–60), intermediate in fetal liver (3–16), and fetal brain (3–14), and lowest in dam brain (0.8–5.6) and fetal plasma (0.3–2.1). In the definitive study, caesarean section examinations were performed following euthanization on gestation day 20 on all surviving females followed by teratologic examination of the fetuses. Drug-related outcomes, including increased activity, secondary hair loss, scabbing, focal swelling, and material around the nose, were exhibited by all groups receiving LAAM. Maternal toxicity was evident as decreased body weights, with maximum reduction at the 6-mg/kg/day dose, and reduction in feed consumption. There was also evidence of developmental toxicity in the form of postimplantaüon losses at all doses of LAAM. There were no deaths attributable to LAAM. No grossly observable visceral or skeletal anomalies related to LAAM were observed in the fetuses. In conclusion, the no-observable-effect level when administered to tolerant rats was less than 2 mg/kg/day with regard to clinical signs, body weight, body weight gain, and feed consumption, and with regard to developmental toxicity as reflected by postimplantaüon losses. Despite maternal and developmental toxicity, there was no evidence of selective fetal toxicity or teratogenic activity attributable to LAAM.

Studies of the Toxicological Potential of Capsinoids: IX. Teratology Studies of Dihydrocapsiate in Rats and Rabbits

2008 ◽  
Vol 27 (3_suppl) ◽  
pp. 119-136 ◽  
Author(s):  
Bruce K. Bernard ◽  
Eri Watanabe ◽  
Terutaka Kodama ◽  
Shoji Tsubuku ◽  
Akira Otabe ◽  
...  
Keyword(s):  
Body Weight ◽  
Sex Ratio ◽  
Food Consumption ◽  
Clinical Signs ◽  
Pathological Finding ◽  
Corpora Lutea ◽  
Test Substance ◽  
Sprague Dawley ◽  
Adverse Effect Level ◽  
Rat Study

In order to determine the safety of dihydrocapsiate (4-hydroxy-3-methoxybenzyl 8-methylnonanoate; CAS no. 205687-03-2), teratology studies were conducted in pregnant Sprague-Dawley rats (18 to 20 animals per group) and pregnant New Zealand white rabbits (20 to 21 animals per group). The test substance was administered by gavage for 11 days, from days 7 to 17 of gestation in rats, and for 13 days from days 6 to 18 of gestation in rabbits, at dose levels of 0 (vehicle), 100, 300, or 1000 mg/kg/day. In the rat study, no deaths occurred in any group and there were no test substance–related changes or abnormalities in clinical signs, body weight, food consumption, or gross pathological findings. There were no test substance–related changes in the number of corpora lutea, number of implantations, index of implantations, index of embryofetal deaths, and number, sex ratio, or body weight of live fetuses at the end of the gestation period and there were no abnormalities in the placentae of live fetuses. There were no test substance–related abnormalities or variations in the external, skeletal, or visceral examinations of live fetuses. There were no abnormalities in ossification. En toto, it was concluded there were no teratogenic effects in the rat study. In the rabbit study, there were no test substance–related effects on clinical signs, body weight, food consumption, or necropsy findings in any group. There were neither test substance–related abortions nor test substance–related effects on the number of corpora lutea, number of implantations, or implantation index in any group. There were no test substance–related effects on the number of dead embryos/fetuses, the number, sex ratio, or body weight of live fetuses, or gross pathological finding of placentae. There were no test substance–related external abnormalities, or incidence of visceral or skeletal abnormalities or variations, and there were no test substance–related effects on the progress of ossification in any group. Based upon these data, the no observed adverse effect level (NOAEL) of dihydrocapsiate for general toxicity in dams, reproductive functions of dams, and embryofetal development was judged to be 1000 mg/kg/day both in rats and rabbits.

Developmental Toxicity of Homobrassinolide in Wistar Rats

2010 ◽  
Vol 29 (5) ◽  
pp. 517-522 ◽  
Author(s):  
Yogeshkumar V. Murkunde ◽  
P. Balakrishna Murthy
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Dose Group ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Oral Gavage ◽  
Fetal Toxicity ◽  
Skeletal Malformations ◽  
Teratogenic Potential

Brassinosteroids (BRs) are close analogues of animal cholesterol. Brassinosteroids have shown their great value as yield promoters of a variety of plants. In view of its steroidal moiety and recent use in agriculture in many countries, the teratogenic potential of homobrassinolide (HBR) was evaluated in Wistar rats. Homobrassinolide was administered by oral gavage at doses 0, 100, and 1000 mg/kg body weight in water during gestation days (GD) 6 to 15 in groups of 20 mated females. Maternal and embryo-fetal toxicity was analyzed by studying the effects such as clinical signs, mortality/morbidity, abortions, body weight, feed consumption, and pregnancy data, gravid uterine weights, implantation losses, litter size, external, visceral, and skeletal malformations. No treatment-related effect was observed on any of the maternal/fetal end points in any dose group. From the results, it can be concluded that HBR is nonteratogenic at doses as high as up to 1000 mg/kg body weight in Wistar rats.

scholarly journals Evaluation of the Developmental Toxicity of Alpha-iso-methylionone in Rats

2007 ◽  
Vol 26 (3) ◽  
pp. 271-276 ◽  
Author(s):  
Valerie T. Politano ◽  
Elise M. Lewis ◽  
Alan M. Hoberman ◽  
Mildred S. Christian ◽  
Robert M. Diener ◽  
...  
Keyword(s):  
Corn Oil ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Feed Consumption ◽  
Corpora Lutea ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Body Weights ◽  
Tissue Changes

Alpha-iso-methylionone, a widely used fragrance ingredient, was evaluated for developmental toxicity in presumed pregnant Sprague-Dawley rats (25/group). Oral dosages of 0, 3, 10, or 30 mg/kg/day alpha-iso-methylionone in corn oil were administered by gavage on gestational days 7 to 17. The presence of spermatozoa and/or a copulatory plug in situ was designated as gestational day. Rats were observed for viability, clinical signs, body weights, and feed consumption. Caesarean sectioning and necropsy occurred on gestational day 21. Uteri were examined for number and distribution of implantations, live and dead fetuses, and early and late resorptions. Numbers of corpora lutea were also recorded. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. No maternal or fetal deaths occurred. No fragrance ingredient–related clinical signs were observed. Feed consumption, body weight gains, gross tissue changes at necropsy, and caesarean section or litter parameters, as well as fetal developmental morphology, were unaffected by dosages of alpha-iso-methylionone as high as 30 mg/kg/day. Based on these data, maternal and developmental no observed adverse effect levels of equal to or greater than 30 mg/kg/day were established for alpha-iso-methylionone. It is concluded that alpha-iso-methylionone is not a developmental toxicant in rats at maternal doses of up to 30 mg/kg/day.

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