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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
one-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Mice to gestation day 18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Study was performed to mainly examine developmental toxicity.
Fertility indices were examined, but dosing did not start until mating.

Data source

Reference
Reference Type:
publication
Title:
Anticonvulsant and reproductive toxicological studies of the imidazole-based histamine H3R antagonist 2-18 in mice
Author:
Salim M Bastaki et al
Year:
2017
Bibliographic source:
Dove Press, 19 January 2018 Volume 2018:12 Pages 179—194

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Male and female mice were allowed to mate and following succesful mating, females were dosed by intraperitoneal injection.
Treatment continued to Gestation Day 18 and animals examined
Although primarily performed as a developmental toxicity study, the study looked at implantation rates and fertility indices
GLP compliance:
not specified
Limit test:
no
Justification for study design:
Primary medical research

Test material

impurity 1
Chemical structure
Reference substance name:
3-(1H-imidazol-4-yl)propyl pent-4-en-1-ylcarbamate
Molecular formula:
C12 H19 N3 O2
IUPAC Name:
3-(1H-imidazol-4-yl)propyl pent-4-en-1-ylcarbamate
Specific details on test material used for the study:
Source Department of Technology and Biotechnology of Drugs (Kraków, Poland)

Test animals

Species:
mouse
Strain:
other: TO, Harlan Research
Sex:
female
Details on test animals or test system and environmental conditions:
Group housed on a 12-h light/dark cycle.
Food and water were available ad libitum.

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
other: Isotonic saline
Details on exposure:
Administered at a volume of 1 mL/kg
Doses per animal were 7.5, 15, 30, and 60 mg/kg
Details on mating procedure:
Adult female mice, about 30 g in weight and about 6 weeks of age, were mated with males in the evening, and vaginal plugs identified in the following morning were taken to indicate successful mating.
Plug positive day was regarded as day 0 of gestation.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Treatment took place on days 8 and 13 with termination on Day 18
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (nominal)
Dose / conc.:
7.5 mg/kg bw/day (nominal)
Dose / conc.:
15 mg/kg bw/day (nominal)
Dose / conc.:
30 mg/kg bw/day (nominal)
Dose / conc.:
60 mg/kg bw/day (nominal)
No. of animals per sex per dose:
Not specific; approximately 10
Control animals:
yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:
Yes
Oestrous cyclicity (parental animals):
No
Sperm parameters (parental animals):
No
Litter observations:
No (terminated before birth)
Postmortem examinations (parental animals):
No
Postmortem examinations (offspring):
No
Reproductive indices:
Yes (implantation sites)
Offspring viability indices:
No

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined

Reproductive function / performance (P0)

Reproductive performance:
no effects observed

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
> 60 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity (P0)

Critical effects observed:
no

Results: F1 generation

General toxicity (F1)

Clinical signs:
not examined

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
> 60 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Remarks on result:
not determinable due to absence of adverse toxic effects

Target system / organ toxicity (F1)

Critical effects observed:
no

Overall reproductive toxicity

Reproductive effects observed:
no

Applicant's summary and conclusion

Conclusions:
The study was performed on a related polyamide to those substances formed in the reaction process and provides an indicator for possible biological effects.
This type of polyamide is closely related to many types of amine / amide found naturally in plants and animals and has bio-pharmacological effect as a metabolite in normal cells.
There was no indication of reduction in viability of young mice and no evidence of resorptions following IP administration.