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EC number: 213-607-2 | CAS number: 993-13-5
Toxicity to reproduction
Administrative data
- Endpoint:
- reproductive toxicity, other
- Remarks:
- other: 90d gavage test in rats including fertility parameters
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2018-12-03 until 2019-03-14
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 020
- Report date:
- 2020
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 408
- Version / remarks:
- 25 June 2018
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
Test material
- Reference substance name:
- Methylphosphonic acid, compound with amidinourea (1:1)
- EC Number:
- 282-758-4
- EC Name:
- Methylphosphonic acid, compound with amidinourea (1:1)
- Cas Number:
- 84402-58-4
- Molecular formula:
- C2H6N4O.CH5O3P
- IUPAC Name:
- methylphosphonic acid, compound with amidinourea (1:1)
- Test material form:
- not specified
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- yes
- No. of animals per sex per dose:
- 10
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, non-treatment-related
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related effects were found for all haematological and coagulation parameters of all male and female dose groups at the end of the treatment period.
A statistical significant decrease of 71.4 % below control was found for the mean value of eosinophils in the male MD dose group and for an increase of monocytes in the female MD dose group (51.1 % above control). The statistical significant changes from control group were found without dose dependency and therefore the single findings are not considered to be of toxicological relevance.
No statistical significances were noted for coagulation parameters in any male and female dose group when compared to control group. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Treatment with the test item had no toxicologically relevant effects on parameters of clinical biochemistry or hormone analysis of males and females in any of the test item-treated groups.
Statistical significance was found in the female HD group for a decrease of 64.87 % below control for total bile acid. Differences between test item-treated males or females and their respective controls showed no dose-dependency or consistency. Additionally, no test item- related effects were noted at histopathological assessment. Therefore, the statistical significance is considered to be of no biological or toxicological relevance. - Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related changes were observed during the histopathological evaluation. All findings recorded in decedent and surviving animals were deemed to be incidental or were within the range of background alterations that may be recorded in animals of this strain and age and in this study type.
Considering histopathological assessment, there were no organ weight changes, gross lesions or histological alterations that could be attributed to the treatment with the test item. Thus, the histopathological NOEL (no observed effect level) could be established at 1000 mg/kg bw. - Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
Effect levels (P0)
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- > 1 000 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effect on fertility parameters in this 90-day oral toxicity study
Target system / organ toxicity (P0)
- Critical effects observed:
- no
Results: F1 generation
General toxicity (F1)
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No test item-related effects were found for all haematological and coagulation parameters of all male and female dose groups at the end of the treatment period.
A statistical significant decrease of 71.4 % below control was found for the mean value of eosinophils in the male MD dose group and for an increase of monocytes in the female MD dose group (51.1 % above control). The statistical significant changes from control group were found without dose dependency and therefore the single findings are not considered to be of toxicological relevance.
No statistical significances were noted for coagulation parameters in any male and female dose group when compared to control group.
Effect levels (F1)
- Remarks on result:
- not measured/tested
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
Overall reproductive toxicity
- Reproductive effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- The no observed adverse effect level (NOAEL) of the test item MPAAU in this sub-chronic study is considered to be 1000 mg/kg body weight/day.
- Executive summary:
In this sub-chronic study, the safety of MPAAU was examined in Wistar rats (four groups of 10 males and 10 females each). The test substance was administered as a solution in tap water by daily oral gavage during 90 consecutive days, at levels of 0 (tap water only), 100, 300 or 1000 mg MPAAU/kg body weight/day.
No test-item related mortality was observed and no adverse effects of the test item were found for male and female clinical observations, functional observations, body weight development, food consumption, haematology and coagulation, clinical biochemistry and hormone analysis, urinalysis, gross macroscopic findings at necropsy, organ weights and histopathology in all treated dose groups.
Especially, there were no effects of the test substance on organ weight, macroscopic examination or histopathology of organs and tissues of the reproductive system (ovaries, oviducts, testes, prostate and seminal vesicles with coagulating glands as a whole, uterus with cervix and vagina). Further, no test item-related adverse effect on thyroid hormone levels (T3, T4, TSH) has been observed.
The no observed adverse effect level (NOAEL) of the test item MPAAU in this sub-chronic study is considered to be 1000 mg/kg body weight/day.
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