Potassium carbamoylcarbamate

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

As summarised in the read-across documentation provided as an attachment to this CSR, potassium allophonate quickly hydrolyses to urea under physiological conditions; therefore, read-across to developmental toxicity information for urea is used to assess developmental toxicity. Teramoto et al. (1981) conducted a study of limited design in which urea failed to produce any teratogenic or systemic effects when pregnant mice and rats were administered a single gavage dose of 2000 mg/kg bw. Furthermore, Seipelt et al. (1969) found no effects on the kidney weights of pups when dams were administered oral doses of urea during pregnancy. Additionally, urea is produced in large quantities by the human body as an endogenous product of normal metabolism. Furthermore, the level of primary and secondary occupational exposures to urea are likely to be insignificant compared to the quantities (20-50 g/day) produced by normal metabolism and present at high concentrations in the blood. Therefore, the weight-of-evidence (WoE) indicates that urea is not a developmental toxicant.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

2 000 mg/kg bw/day

Species:

other: rat and mice

Quality of whole database:

No guideline followed. The study performed with relatively small numbers of animals. Single dose on one dose level.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

No developmental toxicity data are available for potassium allophonate; however, as summarised in the read-across documentation provided as an attachment to this CSR, potassium allophonate quickly hydrolyses to urea under physiological conditions. Therefore, read-across to reproductive/developmental toxicity information on urea is appropriate.

 

In Teramoto et al. (1981), four pregnant rats and ten pregnant mice were administered a single gavage dose of urea at 2000 mg /kg bw on day 12 and day 10 of pregnancy, respectively. Animals were sacrificed eight days later (day 20 for rats and day 18 for mice). For rats and mice, no significant changes were observed regarding the number of implants, number of live fetuses, percent of fetal resorptions, fetal weight or percent fetal malformation. Based on the rat study, no adverse developmental/teratogenicity effects were observed due to a single, high dose urea treatment. In a study summarised in the United States Environmental Protection Agency’s (U.S. EPA) Integrated Risk Information System’s (IRIS) toxicological review of urea, six pregnant rats were administered two doses of urea, totaling 50 g/kg bw/day, during pregnancy (Seipelt et al., 1969). Within 48 hours of birth, pups were sacrificed by decapitation and kidneys were removed and weighed; the right kidney was then dried at 105 deg C and weighed. No evidence of maternal toxicity or effects on the pups' kidney weights were observed in this study.

 

References:

Seipelt, H., Zoellner, K., Hilgenfeld, E. and Grossmann, H. 1969. Studies on kidneys of newborn rats after chronic urea administration to the mother [Article in German]. Zeitschrift Urol. Nephrol., 62(8): 623-7. As cited in: United States Environmental Protection Agency’s (U.S. EPA). 2011. Toxicological Review of Urea: Studies on kidneys of newborn rats after chronic urea administration to the mother. Integrated Risk Information System (IRIS).

 

Teramoto, S., Kaneda, M., Aoyama, H. and Shirasu, Y. 1981. Correlation between the molecular structure of N-alkylureas and N-alkylthioureas and their teratogenic properties. Teratology, 23(3): 335-42.

Justification for selection of Effect on developmental toxicity: via oral route:
Read-across from urea.

Justification for classification or non-classification

The reproductive/developmental toxicity of potassium allophonate was evaluated based on read-across from appropriate studies on urea, since it has been documented that potassium allophonate readily hydrolyses to urea under physiological conditions. Prenatal developmental toxicity studies of limited design are available for rats and mice, none of which found any evidence of developmental toxicity for urea. Therefore, the weight-of-evidence (WoE) from these studies indicates that urea is unlikely to be a developmental toxicant. Additionally, urea is produced in large quantities by the human body as an endogenous product of normal metabolism. Furthermore, the level of primary and secondary occupational exposures to urea are likely to be insignificant compared to the quantities (20-50 g/day) produced by normal metabolism and present at high concentrations in the blood. Therefore, the weight-of-evidence (WoE) indicates that urea is not a developmental toxicant and, based on read-across, potassium allophonate does not warrant classification for the repeat-dose toxicity endpoint.