Oral (Drinking Water) Two-Generation Reproductive Toxicity Study of Bromodichloromethane (BDCM) in Rats

2002 ◽  
Vol 21 (2) ◽  
pp. 115-146 ◽  
Author(s):  
M. S. Christian ◽  
R. G. York ◽  
A. M. Hoberman ◽  
L. C. Fisher ◽  
W. Ray Brown
Keyword(s):  
Drinking Water ◽  
Reproductive Toxicity ◽  
Clinical Signs ◽  
Sperm Parameters ◽  
Feed Consumption ◽  
Exposure Level ◽  
Organ Weights ◽  
Reduced Body ◽  
Body Weights ◽  
Adult Exposure

Bromodichloromethane (BDCM) was tested for reproductive toxicity in a two-generation study in CRL SD rats. Thirty rats/sex/group/generation were continuously provided BDCM in drinking water at 0 (control carrier, reverse osmosis membrane-processed water), 50, 150, and 450 ppm (0,4.1 to 12.6, 11.6 to 40.2, and 29.5 to 109.0 mg/kg/day, respectively). Adult human intake approximates 0.8 μg/kg/day (0.0008 mg/kg/day). P and F1 rats were observed for general toxicity (viability, clinical signs, water and feed consumption, body weights, organ weights [also three weanling F1 and F2 pups/sex/litter], histopathology [10/sex, 0-and 450-ppm exposure groups]) and reproduction (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios, viabilities, maternal behaviors, reproductive organ weights [also three weanling F1 and F2 pups/sex/litter], sperm parameters, and implantations. F1 rats were evaluated for age at vaginal patency or preputial separation. Ten P and F1 rats/sex from the 0-and 450-ppm exposure groups and rats at 50 and 150 ppm with reduced fertility were evaluated for histopathology (gross lesions, testes, intact epididymis, all F1 dams for number of primordial follicles). Developmental parameters in offspring included implantation and pup numbers, sexes, viabilities, body weights, gross external alterations, and reproductive parameters (F1 adults). Toxicologically important, statistically significant effects at 150 and/or 450 ppm included mortality and clinical signs associated with reduced absolute and relative water consumption, reduced body weights and weight gains, and reduced absolute and relative feed consumption (P and F1 rats). Significantly reduced body weights at 150 and 450 ppm were associated with reduced organ weights and increased organ weight ratios (% body and/or brain weight). Histopathology did not identify abnormalities. Small delays in sexual maturation (preputial separation, vaginal patency) and more F1 rats with prolonged diestrus were also attributable to severely reduced pup body weights. Mating, fertility, sperm parameters, and primordial ovarian follicular counts were unaffected. The no-observable-adverse-effect level (NOAEL) and the reproductive and developmental NOAELs for BDCM were at least 50 ppm (4.1 to 12.6 mg/kg/day), 5125 to 15,750 times the human adult exposure level, if delayed sexual maturational associated with severely reduced body weights is considered reproductive toxicity. If considered general toxicity, reproductive and developmental NOAELs for BDCM are greater than 450 ppm (29.5 to 109.0 mg/kg/day), or 36,875 to 136,250 times the human adult exposure level. Regardless, these data indicate that BDCM should not be identified as a risk to human reproductive performance or development of human conceptuses.

Oral (Drinking Water) Two-Generation Reproductive Toxicity Study of Dibromoacetic Acid (DBA) in Rats

2002 ◽  
Vol 21 (4) ◽  
pp. 237-276 ◽  
Author(s):  
M. S. Christian ◽  
R. G. York ◽  
A. M. Hoberman ◽  
J. Frazee ◽  
L. C. Fisher ◽  
...  
Keyword(s):  
Drinking Water ◽  
Body Weight ◽  
Female Rats ◽  
Male Rats ◽  
Feed Consumption ◽  
Organ Weights ◽  
Body Weights ◽  
Group Generation ◽  
Generation Male ◽  
F1 Generation

In a two-generation study of dibromoacetic acid (DBA), Crl SD rats (30 rats/sex/group/generation) were provided DBA in drinking water at 0 (reverse osmosis-deionized water), 50,250, and 650 ppm (0,4.4 to 11.6,22.4 to 55.6, and 52.4 to 132.0 mg/kg/day, respectively; human intake approximates 0.1 μg/kg/day [0.0001 mg/kg/day]). Observations included viability, clinical signs, water and feed consumption, body and organ weights, histopathology, and reproductive parameters (mating, fertility, abortions, premature deliveries, durations of gestation, litter sizes, sex ratios and viabilities, maternal behaviors, reproductive organ weights, sperm parameters and implantation sites, sexual maturation). Histopathological evaluations were performed on at least 10 P and F1 rats/sex at 0 and 650 ppm (gross lesions, testes, intact epididymis; 10 F1 dams at 0, 250, and 650 ppm for primordial follicles). Developmental observations included implantations, pup numbers, sexes, viabilities, body weights, morphology, and reproductive performance. At 50 ppm and higher, both sexes and generations had increased absolute and relative liver and kidneys weights, and female rats in both generations had reduced absolute and relative adrenal weights; adrenal changes were probably associated with physiological changes in water balance. The livers and kidneys (10/sex/group/generation) had no histopathological changes. Other minimal effects at 50 ppm were reduced water consumption and a transient reduction in body weight. At 250 and 650 ppm, DBA reduced parental water consumption, body weight gains, body weights, feed consumption, and pup body weights. P and F1 generation male rats at 250 and 650 ppm had altered sperm production (retained step 19 spermatids in stages IX and X tubules sometimes associated with residual bodies) and some epididymal tubule changes (increased amounts of exfoliated spermatogenic cells/residual bodies in epididymal tubules, atrophy, and hypospermia), although inconsistently and at much lower incidences. Unilateral abnormalities of the epididymis (small or absent epididymis) at 650 ppm in four F1 generation male rats were considered reproductive tract malformations. The no-observable-adverse-effect level (NOAEL) and reproductive and developmental NOAELs for DBA were at least 50 ppm (4.5 to 11.6 mg/kg/day), 45,000 to 116,000 times the human adult exposure level. Reproductive and developmental effects did not occur in female rats exposed to DBA concentrations as high as 650 ppm. Based on the high multiples of human exposure required to produce effects in male rats, DBA should not be identified as a human reproductive or developmental risk.

scholarly journals Two-Generation Reproductive Toxicity Study of Resorcinol Administered Via Drinking Water to Crl:CD(SD) Rats

2008 ◽  
Vol 27 (1) ◽  
pp. 43-57 ◽  
Author(s):  
F. Welsch ◽  
M. D. Nemec ◽  
W. B. Lawrence
Keyword(s):  
Drinking Water ◽  
Adverse Effects ◽  
Case Reports ◽  
Reproductive Toxicity ◽  
Clinical Signs ◽  
Reproductive Function ◽  
Exposure Level ◽  
End Points ◽  
Sd Rats ◽  
Effect Level

The potential adverse effects of resorcinol, delivered via drinking water at 0, 120, 360, 1000, and 3000 mg/L (palatability limit), were assessed in a regulatory guideline compliant two-generation reproduction study in Crl:CD(SD) rats. Expanded end points of thyroid gland (TG) function were added because of clinical case reports indicating human TG toxicity. Average daily resorcinol intake (mg/kg) at the 3000 mg/L concentration was 233 in F0 and F1 males, whereas in females it was 304 (premating/gestation) and 660 (lactation). No resorcinol ingestion-related clinical signs of toxicity were observed. Furthermore, neither gross morphologic anomalies nor effects on reproductive function or thyroid hormone levels were detectable. Body weight reductions occurred in 3000 mg/L F0 and F1 animals and were more pronounced in males. However, there was no evidence of either cumulative toxicity in the second generation or of enhanced sensitivity to resorcinol in pregnant/lactating females. Water intake was lower in 3000 mg/L rats of both generations and intermittently, to a lesser extent, at 1000 mg/L; however, concurrent feed intake and utilization were unaffected. Decreased TG follicular colloid content (conventional histopathology; confirmed by quantitative stereomicroscopy) in the 3000 mg/L F0 males was attributed to resorcinol but not considered adverse. The 3000 mg/L intake level appeared to have caused an adaptive thyroid response to a new homeostatic level with no adverse physiological consequences in either males (the more susceptible gender) or females. There were no differences in TG histology in F0 rats of either sex at 1000 mg/L. Thus, resorcinol intake at maximum palatability via a route and mode relevant to potential human exposures via contaminated drinking water at presently unknown environmental concentrations caused no detectable adverse effects on any reproduction or TG end points. The 3000 mg/L resorcinol exposure level was the no-observed-adverse-effect level (NOAEL) for parental systemic and offspring toxicity, while 1000 mg/L was the no-observed-effect level (NOEL).

scholarly journals Safety evaluation of α-galacto-oligosaccharides for use in infant formulas investigated in neonatal piglets

2017 ◽  
Vol 1 ◽  
pp. 239784731772282 ◽  
Author(s):  
Claire Kruger ◽  
Yuting Zhou ◽  
Bjorn A Thorsrud ◽  
Fanny Morel-Despeisse ◽  
Eric Chappuis
Keyword(s):  
Clinical Chemistry ◽  
Clinical Signs ◽  
Safety Evaluation ◽  
Feed Consumption ◽  
Common Finding ◽  
Infant Formulas ◽  
Organ Weights ◽  
Neonatal Piglets ◽  
Body Weights ◽  
Milk Replacers

Galacto-oligosaccharide (GOS), comprising galactoses with a glucose or sucrose, is a family of nondigestible oligosaccharides. The present study evaluates the safety of an α-GOS product (P-GOS® P) in a neonatal piglet model for 3 weeks. Three days after birth, neonatal piglets were divided into control and treated groups and provided with swine milk replacers in the absence and presence of 8 mg/mL—of the α-GOS product, respectively. An increase in the weight of the large intestines in treated males was noted, which is a common finding in studies of animals fed nondigestible oligosaccharides. There were no α-GOS product-related adverse effects in the piglets in terms of clinical signs, body weights, feed consumption, clinical chemistry, hematology, organ weights, or histopathology. The study demonstrated that formula supplemented with 8 mg/mL of P-GOS P is safe and well tolerated in neonatal piglets and supports the safe use of P-GOS P in infant formulas.

scholarly journals Evaluation of the Developmental Toxicity of 1-(1,2,3,4,5,6,7,8-Octahydro-2,3,8, 8-Tetramethyl-2-Naphthalenyl) Ethanone (OTNE) in Rats

2009 ◽  
Vol 28 (3) ◽  
pp. 213-218 ◽  
Author(s):  
Valerie T. Politano ◽  
Charlene S. Letizia ◽  
Mildred S. Christian ◽  
Robert M. Diener ◽  
Anne Marie Api
Keyword(s):  
Body Weight ◽  
Soft Tissue ◽  
Developmental Toxicity ◽  
Clinical Signs ◽  
Significant Degree ◽  
Feed Consumption ◽  
Exposure Level ◽  
Sprague Dawley ◽  
Body Weights ◽  
Weight Gains

The developmental toxicity of 1-(1,2,3,4,5,6,7,8-Octahydro-2,3,8,8-tetramethyl-2-naphthalenyl) ethanone (OTNE), a widely used fragrance ingredient, was evaluated in pregnant Sprague-Dawley rats (25/group) gavaged with dosages of 0 (water), 96, 240, or 480 mg/kg/d on days 7 through 17 of gestation (GDs 7–17). Rats were observed for clinical signs, abortions, premature deliveries, body weights, and feed intake. Caesarean section and necropsy were performed on GD 21. Fetuses were weighed and examined for gender, gross external changes, and soft tissue or skeletal alterations. No deaths or premature deliveries were attributed to OTNE. OTNE-related clinical signs included significantly increased incidences of excessive salivation in all 3 treatment groups, and urine-stained abdominal fur in the high dosage group. Mean body weight gains were significantly reduced by all OTNE dosages on GDs 7–10, while at 480 mg/kg/d, significant reductions continued through the remainder of the dosage period. Feed consumption generally paralleled body weight gains. Fetal body weights were reduced by 480 mg/kg/d, but not to a statistically significant degree. No fetal gross external, soft tissue, or skeletal malformations or variations were attributable to OTNE. Based on these data, maternal and developmental no-observable-adverse-effect-levels (NOAELs) of 240 mg/kg/d were established for OTNE. It was concluded that OTNE is not a developmental toxicant in rats under the conditions of this study, and that a margin of safety greater than 2700 exists between reversible developmental delays in rats and the calculated daily human exposure level of 0.086 mg/kg/d.

Oral 1-Generation Rat Reproduction Study of Isobornyl Acetate: An Evaluation Through Sexual Maturity in the F1 Generation

2017 ◽  
Vol 36 (3) ◽  
pp. 252-259 ◽  
Author(s):  
Valerie T. Politano ◽  
Elise M. Lewis ◽  
Alan M. Hoberman ◽  
Robert M. Diener ◽  
Anne Marie Api ◽  
...  
Keyword(s):  
Sexual Maturity ◽  
Ovarian Follicle ◽  
Reproductive Toxicity ◽  
Clinical Signs ◽  
Female Rats ◽  
Feed Consumption ◽  
Male And Female Rats ◽  
Body Weights ◽  
Reproduction Study ◽  
F1 Generation

Reproductive toxicity of isobornyl acetate (IA), a widely used fragrance ingredient, was investigated in a 1-generation reproduction study in which 25 Crl: CD (Sprague-Dawley) rats/sex/group were gavaged with dosages of 0 (corn oil vehicle), 30, 100, or 300 mg/kg/d during premating, mating, gestation, and lactation. After weaning, 25 F1 generation pups/sex/dosage group were randomly selected for evaluation until sexual maturity. The following parameters were evaluated in P generation males and females: viability, clinical signs, body weights, feed consumption, mating and fertility, organ weights, gross and microscopic observations, sperm assessments (motility and concentration), natural delivery and litter observations, and ovarian follicle counts. In F1 generation pups, viability, body weights, sexual maturation, anogenital distance (days 1 and 22 postpartum), nipple eruption (day 12 postpartum), and gross necropsy observations were recorded. Isobornyl acetate did not adversely affect any of the investigated parameters. Based on the results of this investigation, the no observable adverse effect level (NOAEL) for toxicity of IA is considered to be 300 mg/kg/d. Increased incidences of excess salivation occurred in P generation male and female rats at 100 and/or 300 mg/kg/d throughout the dosage period, and low incidences of urine-stained abdominal fur were seen in females at 300 mg/kg/d during the gestation period. These clinical signs were not considered as adverse effects of IA administration. Thus, the NOAEL for reproductive toxicity in the P generation rats and the NOAEL for viability and growth of the F1 generation offspring is considered to be ≥300 mg/kg/d.

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.

Reduction of Aflatoxins by Korean Soybean Paste and Its Effect on Cytotoxicity and Reproductive Toxicity—Part 3. Inhibitory Effects of Korean Soybean Paste (Doen-jang) on Aflatoxin Toxicity in Laying Hens and Aflatoxin Accumulation in Their Eggs

2003 ◽  
Vol 66 (5) ◽  
pp. 866-873 ◽  
Author(s):  
JONG-GYU KIM ◽  
YONG-WOOK LEE ◽  
PAN-GYI KIM ◽  
WOO-SUP ROH ◽  
HIDEHARU SHINTANI
Keyword(s):  
Body Weight ◽  
Serum Calcium ◽  
Egg Production ◽  
Laying Hens ◽  
Reproductive Toxicity ◽  
Lactic Dehydrogenase ◽  
Organ Weights ◽  
Reduced Body ◽  
Soybean Paste ◽  
Aflatoxin Accumulation

This study was conducted to determine the effects of Korean soybean paste (doen-jang [dwen-jahng]) (at concentrations of 0.5, 1, and 5%) on the toxicity of 500 ppb of aflatoxin in the diets of 60 laying hens (Isa Brown) divided into five groups and treated from week 15 to week 67. The aflatoxin-treated hens exhibited many deleterious effects, including reduced body weight; increased relative organ weights; decreased egg production; aflatoxin accumulation in eggs; decreased serum calcium, phosphorus, and alanino amonotransferase (ALT) levels; increased serum gammaglutamil transferase and lactic dehydrogenase levels; and, most significantly, severely altered cell foci and sinusoid dilatation in the liver, relative to control hens. The feeding of 1% soybean paste to hens reduced the adverse effects of aflatoxin on body weight, relative organ weights, egg production, and aflatoxin accumulation in eggs and improved serum calcium and ALT levels and the histopathological lesions of the liver. The feeding of 5% soybean paste to hens resulted in higher levels of the same types of improvements, especially with regard to the histopathological findings for the liver. On the basis of these results, it was suggested that a diet including 5% (and in some cases only 1%) Korean soybean paste protected laying hens and their eggs from the major deleterious effects of 500 μg of aflatoxin per kg of diet and from aflatoxin accumulation. These results indicate that dietary supplementation with Korean soybean paste reduces aflatoxin toxicity in laying hens that ultimately produce human foods such as eggs and poultry.

Reproductive Toxicity Evaluation of the Dental Resin Monomer Bisphenol A Glycidyl Methacrylate (CAS 1565-94-2) in Mice

2013 ◽  
Vol 32 (6) ◽  
pp. 415-425 ◽  
Author(s):  
Lori H. Moilanen ◽  
Janell K. Dahms ◽  
Alan M. Hoberman
Keyword(s):  
Bisphenol A ◽  
Glycidyl Methacrylate ◽  
Reproductive Toxicity ◽  
Sperm Concentration ◽  
Clinical Signs ◽  
Dental Resin ◽  
Male And Female ◽  
Toxicity Potential ◽  
Body Weights ◽  
Estrous Cyclicity

The reproductive toxicity potential of the dental resin monomer bisphenol A glycidyl methacrylate (BisGMA; CASRN 1565-94-2) was investigated in male and female Crl: CD1(ICR) mice, 4 dosage groups, and 25 mice/sex/group. Formulations of BisGMA (0, 0.008, 0.08, or 0.8 mg/kg/d) in 0.8% ethanol in deionized water were intubated once daily beginning 28 days before cohabitation and continuing through mating (males) or through gestation day 17. The following parameters were evaluated: viability, clinical signs, body weights, estrous cyclicity, necropsy observations, organ weights, sperm concentration/motility/morphology, cesarean sectioning and litter observations, and histopathological evaluation of select tissues. No deaths or clinical signs related to BisGMA occurred. No significant changes in male and female body weights and body weight gains were recorded at any of the administered dosages of BisGMA. All mating and fertility parameters, and all litter and fetal data, were considered to be unaffected by dosages of BisGMA as high as 0.8 mg/kg/d. Gross or histopathologic tissue changes attributable to the test article were not observed. Reproductive and developmental no observed effect levels (NOAELs) for BisGMA were 0.8 mg/kg/d, the highest dose tested. Comparison of this NOAEL value to published probabilistic estimates of human BisGMA exposure from dental products suggests a margin of safety of at least 280- to nearly 2000-fold. Under the conditions of this study, BisGMA is not a reproductive toxicant.

The Toxicity of Cyclopiazonic Acid in Weaned Pigs

1984 ◽  
Vol 21 (4) ◽  
pp. 418-424 ◽  
Author(s):  
L. G. Lomax ◽  
R. J. Cole ◽  
J. W. Dorner
Keyword(s):  
Body Weight ◽  
Clinical Signs ◽  
Cyclopiazonic Acid ◽  
Gastric Ulcers ◽  
Reduced Body ◽  
Hepatocellular Necrosis ◽  
Body Weights ◽  
Renal Tubular ◽  
Crossbred Pigs ◽  
Small And Large Intestine

Five- to six-week-old crossbred pigs weighing 5 to 14 kg were given purified cyclopiazonic acid at dosages of 10, 1.0, 0.1, and 0.01 mg/kg body weight orally for 14 days. Clinical signs observed by day 7 in pigs given 10 mg/kg body weight were weakness, inactivity, anorexia, rough hair coats, and reduced body weights. These pigs also developed diarrhea during week 2 of the experiment. The pigs given 1.0 mg/kg body weight had rough hair coats and were moderately inactive during the second week of the experiment. At necropsy, lesions were observed only in pigs given 10 and 1.0 mg/kg body weight of cyclopiazonic acid. Lesions were gastric ulcers, mucosal hyperemia, and hemorrhage throughout the small and large intestine in pigs given 10 mg/kg body weight of cyclopiazonic acid. The pigs also had yellow, fibrinonecrotic material in the lumen of the small intestine and pale livers. One pig given 1.0 mg/kg body weight had gastric ulceration. Microscopic lesions in pigs given 10 mg/kg body weight were necrotizing gastroenteritis, focal hepatocellular necrosis, hepatic peripheral lobular fatty change, and focal renal tubular nephrosis with focal suppurative tubulointerstitial nephritis. Pigs given 1.0 mg/kg body weight of cyclopiazonic acid had necrotizing gastritis and villous blunting in the jejunum and ileum.

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.

Sign in / Sign up

Export Citation Format

Share Document