Susceptible period for the teratogenicity of di-n-butyltin dichloride in rats

Potential teratogenicity of di‐n‐butyltin dichloride and other dibutyltin compounds

“…A compilation of the most important data is given in Tables V and VI. In contrast to the data of Ema et al [1], all pregnant rats survived the dosing with 10 and 15 mg DBT-dA/kg body weight. Maternal weight was reported to be reduced on day 20 (no data on maternal weight gain were provided) at the highest dose level or 15 mg/kg only.…”

“…The elevated occurrence of ankyloglossia is remarkable (12/36 fetuses, at 20 mg/kg during days 7-9 of pregnancy), but other defects, e.g., omphalocele, were noticed at an even higher rate under these extreme experimental conditions. Although the documentation of the results of the study of Noda et al [4] is suboptimal, the results are in accord with those of Ema et al [3]. When administered on day 8 of pregnancy, a clear increase in the number of malformations was only observed at a dose of 22 mg DBT-dA/kg body weight, although a small, not statistically significant trend was observed at 15 mg/kg (2/117 fetuses with manible/lip/tongue defects).…”

“…It is noteworthy that cleft mandible and ankyloglossia, rather uncommon abnormalities, were reported to occur in all three prenatal toxicity studies that have been conducted with dibutyltin compounds in different laboratories and varying experimental conditions. Such ankyloglossia occurred at high frequency (10/125 fetuses) in the study by Ema et al [1] at highly toxic doses. Cleft mandible or ankyloglossia were reported by Noda et al [2] at a high incidence (43/179 fetuses) at the maternally toxic dose of 10 mg/kg body weight but also in one case (1/196) at 5 mg/kg.…”

Potential teratogenicity of di‐n‐butyltin dichloride and other dibutyltin compounds

“…A compilation of the most important data is given in Tables V and VI. In contrast to the data of Ema et al [1], all pregnant rats survived the dosing with 10 and 15 mg DBT-dA/kg body weight. Maternal weight was reported to be reduced on day 20 (no data on maternal weight gain were provided) at the highest dose level or 15 mg/kg only.…”

“…The elevated occurrence of ankyloglossia is remarkable (12/36 fetuses, at 20 mg/kg during days 7-9 of pregnancy), but other defects, e.g., omphalocele, were noticed at an even higher rate under these extreme experimental conditions. Although the documentation of the results of the study of Noda et al [4] is suboptimal, the results are in accord with those of Ema et al [3]. When administered on day 8 of pregnancy, a clear increase in the number of malformations was only observed at a dose of 22 mg DBT-dA/kg body weight, although a small, not statistically significant trend was observed at 15 mg/kg (2/117 fetuses with manible/lip/tongue defects).…”

“…It is noteworthy that cleft mandible and ankyloglossia, rather uncommon abnormalities, were reported to occur in all three prenatal toxicity studies that have been conducted with dibutyltin compounds in different laboratories and varying experimental conditions. Such ankyloglossia occurred at high frequency (10/125 fetuses) in the study by Ema et al [1] at highly toxic doses. Cleft mandible or ankyloglossia were reported by Noda et al [2] at a high incidence (43/179 fetuses) at the maternally toxic dose of 10 mg/kg body weight but also in one case (1/196) at 5 mg/kg.…”

Dibutyltin Dichloride Retards Leydig Cell Developmental Regeneration in Adult Rat Testis

“…Previous studies reported teratogenicity and lethality of DBTCl at doses ≥ 20 mg/kg, and the present study extended DBTCl toxicity to 5 mg/kg with regard to male steroidogenesis ( Ema et al, 1992 ; Furukawa et al, 2017 ). Though no report concerning the in vivo effects of DBTCl on Leydig cell was available, there were indeed some in vitro studies.…”

Simulated gastric hydrolysis and developmental toxicity of dibutyltin bis(2‐ethylhexyl thioglycolate) in rats

“…First, simulated gastric hydrolysis data (Schilt & van Zondervan, 2004; Yoder, 2000a; Yoder, 2000b) suggested that alkyltin esters of several classes were hydrolyzed to their respective chlorides in acidic media. Second, the ankyloglossia observed in fetuses exposed to DBTC (Ema et al, 1992) was also observed after exposure on Gestation Day 8 to equimolar doses of dibutyltin alkyl esters (80 μmol/kg on GD8), which supported the hypothesis that the esters were hydrolyzed to DBTC in vivo to produce the adverse fetal outcomes (Noda et al, 1993).…”

Potential teratogenicity of di‐n‐butyltin dichloride and other dibutyltin compounds

“…A compilation of the most important data is given in Tables V and VI. In contrast to the data of Ema et al [1], all pregnant rats survived the dosing with 10 and 15 mg DBT-dA/kg body weight. Maternal weight was reported to be reduced on day 20 (no data on maternal weight gain were provided) at the highest dose level or 15 mg/kg only.…”

“…The elevated occurrence of ankyloglossia is remarkable (12/36 fetuses, at 20 mg/kg during days 7-9 of pregnancy), but other defects, e.g., omphalocele, were noticed at an even higher rate under these extreme experimental conditions. Although the documentation of the results of the study of Noda et al [4] is suboptimal, the results are in accord with those of Ema et al [3]. When administered on day 8 of pregnancy, a clear increase in the number of malformations was only observed at a dose of 22 mg DBT-dA/kg body weight, although a small, not statistically significant trend was observed at 15 mg/kg (2/117 fetuses with manible/lip/tongue defects).…”

“…It is noteworthy that cleft mandible and ankyloglossia, rather uncommon abnormalities, were reported to occur in all three prenatal toxicity studies that have been conducted with dibutyltin compounds in different laboratories and varying experimental conditions. Such ankyloglossia occurred at high frequency (10/125 fetuses) in the study by Ema et al [1] at highly toxic doses. Cleft mandible or ankyloglossia were reported by Noda et al [2] at a high incidence (43/179 fetuses) at the maternally toxic dose of 10 mg/kg body weight but also in one case (1/196) at 5 mg/kg.…”

Dibutyltin Dichloride Retards Leydig Cell Developmental Regeneration in Adult Rat Testis

“…Previous studies reported teratogenicity and lethality of DBTCl at doses ≥ 20 mg/kg, and the present study extended DBTCl toxicity to 5 mg/kg with regard to male steroidogenesis ( Ema et al, 1992 ; Furukawa et al, 2017 ). Though no report concerning the in vivo effects of DBTCl on Leydig cell was available, there were indeed some in vitro studies.…”

Simulated gastric hydrolysis and developmental toxicity of dibutyltin bis(2‐ethylhexyl thioglycolate) in rats

“…First, simulated gastric hydrolysis data (Schilt & van Zondervan, 2004; Yoder, 2000a; Yoder, 2000b) suggested that alkyltin esters of several classes were hydrolyzed to their respective chlorides in acidic media. Second, the ankyloglossia observed in fetuses exposed to DBTC (Ema et al, 1992) was also observed after exposure on Gestation Day 8 to equimolar doses of dibutyltin alkyl esters (80 μmol/kg on GD8), which supported the hypothesis that the esters were hydrolyzed to DBTC in vivo to produce the adverse fetal outcomes (Noda et al, 1993).…”

Potential teratogenicity of di‐n‐butyltin dichloride and other dibutyltin compounds

“…A compilation of the most important data is given in Tables V and VI. In contrast to the data of Ema et al [1], all pregnant rats survived the dosing with 10 and 15 mg DBT-dA/kg body weight. Maternal weight was reported to be reduced on day 20 (no data on maternal weight gain were provided) at the highest dose level or 15 mg/kg only.…”

“…The elevated occurrence of ankyloglossia is remarkable (12/36 fetuses, at 20 mg/kg during days 7-9 of pregnancy), but other defects, e.g., omphalocele, were noticed at an even higher rate under these extreme experimental conditions. Although the documentation of the results of the study of Noda et al [4] is suboptimal, the results are in accord with those of Ema et al [3]. When administered on day 8 of pregnancy, a clear increase in the number of malformations was only observed at a dose of 22 mg DBT-dA/kg body weight, although a small, not statistically significant trend was observed at 15 mg/kg (2/117 fetuses with manible/lip/tongue defects).…”

“…It is noteworthy that cleft mandible and ankyloglossia, rather uncommon abnormalities, were reported to occur in all three prenatal toxicity studies that have been conducted with dibutyltin compounds in different laboratories and varying experimental conditions. Such ankyloglossia occurred at high frequency (10/125 fetuses) in the study by Ema et al [1] at highly toxic doses. Cleft mandible or ankyloglossia were reported by Noda et al [2] at a high incidence (43/179 fetuses) at the maternally toxic dose of 10 mg/kg body weight but also in one case (1/196) at 5 mg/kg.…”

Dibutyltin Dichloride Retards Leydig Cell Developmental Regeneration in Adult Rat Testis

“…Previous studies reported teratogenicity and lethality of DBTCl at doses ≥ 20 mg/kg, and the present study extended DBTCl toxicity to 5 mg/kg with regard to male steroidogenesis ( Ema et al, 1992 ; Furukawa et al, 2017 ). Though no report concerning the in vivo effects of DBTCl on Leydig cell was available, there were indeed some in vitro studies.…”

Simulated gastric hydrolysis and developmental toxicity of dibutyltin bis(2‐ethylhexyl thioglycolate) in rats

“…First, simulated gastric hydrolysis data (Schilt & van Zondervan, 2004; Yoder, 2000a; Yoder, 2000b) suggested that alkyltin esters of several classes were hydrolyzed to their respective chlorides in acidic media. Second, the ankyloglossia observed in fetuses exposed to DBTC (Ema et al, 1992) was also observed after exposure on Gestation Day 8 to equimolar doses of dibutyltin alkyl esters (80 μmol/kg on GD8), which supported the hypothesis that the esters were hydrolyzed to DBTC in vivo to produce the adverse fetal outcomes (Noda et al, 1993).…”