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Effects on fertility

Description of key information

A study conducted with the substance N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea] (EC # 451-060-3, also known as KY-UN), which is within the category definition of the MDI category is read across to members of the polyurea MDI category.

The substance was studied in a Reproduction/Developmental Toxicity Screening Test according to OECD 421 and EPA OPPTS 870.550 guidelines and in accordance with GLP. Based on the results of this test, a parental, reproduction and developmental No Observed Adverse Effect Level (NOAEL) of at least 1000 mg/kg bw/day was established, the highest dose tested.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Good
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A study conducted with the substance N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea] (EC # 451-060-3, also known as KY-UN), which is within the category definition of the MDI category is read across to members of the polyurea MDI category.

N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea] was studied in a reproduction/developmental toxicity screening test according to OECD 421 and EPA OPPTS 870.550 guidelines and in accordance with GLP principles. Wistar Han rats were treated with KY-UN by daily oral gavage at dose levels of 100, 300 and 1000 mg/kg bw/day. The rats of the control group received the vehicle, 0.5% Methylcellulose, alone. Males were treated for 2 weeks prior to mating, during mating, and up to termination (a total of 29 days). Females that delivered offspring were treated for 2 weeks prior to mating, during mating, during post-coitum, and at least 13-15 days of lactation (a total of 50-56 days). Females that failed to deliver pups were treated for a total of 42-53 days. Test formulations prepared were considered homogeneous at the concentrations tested and analysis of the formulations revealed acceptable levels of accuracy. Test formulations prepared were considered stable, for at least 5 hours at room temperature.

No parental toxicity was observed up to and including the highest dose level tested (1000 mg/kg bw/ day). No toxicologically significant changes were noted in any of the parameters investigated in this study (i.e. clinical appearance, body weight, food consumption, haematology investigations (including met-haemoglobin), male T4 thyroid hormone levels, macroscopic examination, organ weights, and microscopic examination).

Also, no reproduction toxicity was observed up to and including the highest dose level tested (1000 mg/ kg bw/day). No toxicologically significant changes were noted in any of the reproductive parameters investigated in this study (i.e. mating and fertility indices, precoital time, number of implantations, oestrous cycle, spermatogenic profiling, and histopathological examination of reproductive organs).

Effects on developmental toxicity

Description of key information

A study conducted with the substance N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea], which is within the category definition of the MDI category is read across to members of the polyurea MDI category.

N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea] was studied in a Reproduction/Developmental Toxicity Screening Test according to according to OECD 421 and EPA OPPTS 870.550 guidelines and in accordance with GLP. Based on the results of this test, a parental, reproduction and developmental No Observed Adverse Effect Level (NOAEL) of at least 1000 mg/kg bw/day for KY-UN was established.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Good
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

A study conducted with the substance N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea] (EC # 451-060-3, also known as KY-UN), which is within the category definition of the MDI category is read across to members of the polyurea MDI category.

In the reproduction/developmental toxicity screening test conducted with N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea], no developmental toxicity was observed up to and including the highest dose level tested (1000 mg/kg bw/day). In the control group, two females were found not to be pregnant and, on the day of parturition, one of the remaining eight females had implantations only. Consequently, only seven of the intended eight control litters were available for evaluation. However, it is considered that sufficient information was available from the seven control litters for a thorough toxicological evaluation. No toxicologically significant changes were noted in any of the developmental parameters investigated in this study (i.e. gestation, viability and lactation indices, duration of gestation, parturition, sex ratio, maternal care and early postnatal pup development consisting of mortality, clinical signs, body weight, anogenital distance, areola/nipple retention, T4 thyroid hormone levels and macroscopic examination).

Justification for classification or non-classification

MDI category members are not classified as no adverse reproductive or developmental toxicity effects observed in the study conducted with the substance N,N''-(methylenedi-4,1-phenylene)bis[N'-octylurea], a structural analogue substance that meets the MDI category definition.

Additional information

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