Absence of embryotoxic effects in rats with three quarternary ammonium compounds (Cationic surfactants)

Systematic assessment of quaternary ammonium compounds for the potential to elicit developmental and reproductive effects

“…Another study by Herron et al ( 2019 ) was excluded from our assessment because, although conducted in mice, evaluations were done at 3 min to 3 hr post‐dosing and involved multi‐omics investigation of neonatal brain tissues; this study was thus considered a mechanistic evaluation and of secondary value to the analysis. An additional study (Palmer, Bottomley, Edwards, & Clark, 1983 ) used topical application to pregnant rats of three QUATs that are rarely, if ever, used commercially: dimethyldistearylammonium chloride, benzyldimethylstearylammonium chloride, and trimethylstearylammonium chloride. Because the bulk of studies available for examination involved ADBAC and DDAC, the QUATS most commonly used in commercial and household settings, the study by Palmer et al ( 1983 ), which reported an absence of embryotoxic effects, was not further considered.…”

“…An additional study (Palmer, Bottomley, Edwards, & Clark, 1983 ) used topical application to pregnant rats of three QUATs that are rarely, if ever, used commercially: dimethyldistearylammonium chloride, benzyldimethylstearylammonium chloride, and trimethylstearylammonium chloride. Because the bulk of studies available for examination involved ADBAC and DDAC, the QUATS most commonly used in commercial and household settings, the study by Palmer et al ( 1983 ), which reported an absence of embryotoxic effects, was not further considered.…”

Systematic assessment of quaternary ammonium compounds for the potential to elicit developmental and reproductive effects

“…Another study by Herron et al ( 2019 ) was excluded from our assessment because, although conducted in mice, evaluations were done at 3 min to 3 hr post‐dosing and involved multi‐omics investigation of neonatal brain tissues; this study was thus considered a mechanistic evaluation and of secondary value to the analysis. An additional study (Palmer, Bottomley, Edwards, & Clark, 1983 ) used topical application to pregnant rats of three QUATs that are rarely, if ever, used commercially: dimethyldistearylammonium chloride, benzyldimethylstearylammonium chloride, and trimethylstearylammonium chloride. Because the bulk of studies available for examination involved ADBAC and DDAC, the QUATS most commonly used in commercial and household settings, the study by Palmer et al ( 1983 ), which reported an absence of embryotoxic effects, was not further considered.…”

“…An additional study (Palmer, Bottomley, Edwards, & Clark, 1983 ) used topical application to pregnant rats of three QUATs that are rarely, if ever, used commercially: dimethyldistearylammonium chloride, benzyldimethylstearylammonium chloride, and trimethylstearylammonium chloride. Because the bulk of studies available for examination involved ADBAC and DDAC, the QUATS most commonly used in commercial and household settings, the study by Palmer et al ( 1983 ), which reported an absence of embryotoxic effects, was not further considered.…”

Quaternary ammonium compounds: perspectives on benefits, hazards, and risk

“…Three non-guideline studies of QACs have been published, two in mice and one in rats, that show no reproductive and no developmental toxicity. [40][41][42] More recently, Melin et al 43,44 and Hrubec et al 45 conducted non-guideline developmental toxicity and reproductive toxicity studies on a mixture of ADBAC and DDAC that reported adverse effects on fetal development and fertility in mice, a non-standard species not part of any regulatory safety assessment program. These results conflict with those studies in rats and rabbits on which the EPA 10,11 based their assessments.…”

“…This is an important point as the effect observed is concerning, but there is a significant lack of evidence to clearly indicate that it is a persistent, test material effect. As a follow-up to the study above, mating pairs of mice were administered 0, 60, or 120 mg/kg/day of a combined ADBAC/DDAC formulation for 8 weeks (Hrubec et al 42 ). Exposure to the combined ADBAC/DDAC formulation resulted in an increase in NTDs in GD 10 mouse embryos (120 mg/kg/day), a decrease in fetal and placental weight in GD 18 mouse embryos (60 mg/kg/day), and an increase in late gestation resorptions (120 mg/kg/day).…”

Systematic assessment of quaternary ammonium compounds for the potential to elicit developmental and reproductive effects

“…Another study by Herron et al ( 2019 ) was excluded from our assessment because, although conducted in mice, evaluations were done at 3 min to 3 hr post‐dosing and involved multi‐omics investigation of neonatal brain tissues; this study was thus considered a mechanistic evaluation and of secondary value to the analysis. An additional study (Palmer, Bottomley, Edwards, & Clark, 1983 ) used topical application to pregnant rats of three QUATs that are rarely, if ever, used commercially: dimethyldistearylammonium chloride, benzyldimethylstearylammonium chloride, and trimethylstearylammonium chloride. Because the bulk of studies available for examination involved ADBAC and DDAC, the QUATS most commonly used in commercial and household settings, the study by Palmer et al ( 1983 ), which reported an absence of embryotoxic effects, was not further considered.…”

“…An additional study (Palmer, Bottomley, Edwards, & Clark, 1983 ) used topical application to pregnant rats of three QUATs that are rarely, if ever, used commercially: dimethyldistearylammonium chloride, benzyldimethylstearylammonium chloride, and trimethylstearylammonium chloride. Because the bulk of studies available for examination involved ADBAC and DDAC, the QUATS most commonly used in commercial and household settings, the study by Palmer et al ( 1983 ), which reported an absence of embryotoxic effects, was not further considered.…”

Quaternary ammonium compounds: perspectives on benefits, hazards, and risk

“…Three non-guideline studies of QACs have been published, two in mice and one in rats, that show no reproductive and no developmental toxicity. [40][41][42] More recently, Melin et al 43,44 and Hrubec et al 45 conducted non-guideline developmental toxicity and reproductive toxicity studies on a mixture of ADBAC and DDAC that reported adverse effects on fetal development and fertility in mice, a non-standard species not part of any regulatory safety assessment program. These results conflict with those studies in rats and rabbits on which the EPA 10,11 based their assessments.…”

“…This is an important point as the effect observed is concerning, but there is a significant lack of evidence to clearly indicate that it is a persistent, test material effect. As a follow-up to the study above, mating pairs of mice were administered 0, 60, or 120 mg/kg/day of a combined ADBAC/DDAC formulation for 8 weeks (Hrubec et al 42 ). Exposure to the combined ADBAC/DDAC formulation resulted in an increase in NTDs in GD 10 mouse embryos (120 mg/kg/day), a decrease in fetal and placental weight in GD 18 mouse embryos (60 mg/kg/day), and an increase in late gestation resorptions (120 mg/kg/day).…”

Systematic assessment of quaternary ammonium compounds for the potential to elicit developmental and reproductive effects

“…Another study by Herron et al ( 2019 ) was excluded from our assessment because, although conducted in mice, evaluations were done at 3 min to 3 hr post‐dosing and involved multi‐omics investigation of neonatal brain tissues; this study was thus considered a mechanistic evaluation and of secondary value to the analysis. An additional study (Palmer, Bottomley, Edwards, & Clark, 1983 ) used topical application to pregnant rats of three QUATs that are rarely, if ever, used commercially: dimethyldistearylammonium chloride, benzyldimethylstearylammonium chloride, and trimethylstearylammonium chloride. Because the bulk of studies available for examination involved ADBAC and DDAC, the QUATS most commonly used in commercial and household settings, the study by Palmer et al ( 1983 ), which reported an absence of embryotoxic effects, was not further considered.…”

“…An additional study (Palmer, Bottomley, Edwards, & Clark, 1983 ) used topical application to pregnant rats of three QUATs that are rarely, if ever, used commercially: dimethyldistearylammonium chloride, benzyldimethylstearylammonium chloride, and trimethylstearylammonium chloride. Because the bulk of studies available for examination involved ADBAC and DDAC, the QUATS most commonly used in commercial and household settings, the study by Palmer et al ( 1983 ), which reported an absence of embryotoxic effects, was not further considered.…”

Quaternary ammonium compounds: perspectives on benefits, hazards, and risk

“…Three non-guideline studies of QACs have been published, two in mice and one in rats, that show no reproductive and no developmental toxicity. [40][41][42] More recently, Melin et al 43,44 and Hrubec et al 45 conducted non-guideline developmental toxicity and reproductive toxicity studies on a mixture of ADBAC and DDAC that reported adverse effects on fetal development and fertility in mice, a non-standard species not part of any regulatory safety assessment program. These results conflict with those studies in rats and rabbits on which the EPA 10,11 based their assessments.…”

“…This is an important point as the effect observed is concerning, but there is a significant lack of evidence to clearly indicate that it is a persistent, test material effect. As a follow-up to the study above, mating pairs of mice were administered 0, 60, or 120 mg/kg/day of a combined ADBAC/DDAC formulation for 8 weeks (Hrubec et al 42 ). Exposure to the combined ADBAC/DDAC formulation resulted in an increase in NTDs in GD 10 mouse embryos (120 mg/kg/day), a decrease in fetal and placental weight in GD 18 mouse embryos (60 mg/kg/day), and an increase in late gestation resorptions (120 mg/kg/day).…”