4-morpholinopropanesulphonic acid

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

A study according OECD TG 422 with the structurally similar substance CAS 1266615-59-1 is available. The NOAEL for systemic toxicity of male/female rats was determined to be 1000 mg/kg bw/day. The NOAEL for reproductive performance of male/female rats and for F1 Offspring was determined to be 1000 mg/kg bw/day, respectively (reference 7.8.1 -1).

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Please refer to section 13 for Read-Across Justification.

Reason / purpose for cross-reference:

read-across source

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No test substance related adverse effects were observed up to the highest dose tested.

Key result

Critical effects observed:

no

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No test substance related adverse effects were observed up to the highest dose tested.

Key result

Critical effects observed:

no

Key result

Reproductive effects observed:

no

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:

The study was performed according to OECD TG 422 (GLP).

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

No study data with the test item is available for toxicity after repeated administration. Therefore, a read-across to the substance CAS 1266615-59-1 with a very similar chemical structure and comparable physico-chemical parameters is used to evaluate the potential of the test item to cause reproductive toxicity.

A study according OECD TG 422 was performed with the structurally similar substance CAS 1266615-59 -1 to investigate possible effects of the test item on reproduction and development when repeatedly administered orally to rats compared to control animals. Four groups of Wistar rats consisting of 12 animals per group and sex were administered by gavage once daily doses of 0 (vehicle only), 100, 300 and 1000 mg/kg bw/day. The suitability of distilled water as vehicle for the test item was analytically verified up front as the test item was stable in distilled water at room temperature for at least four days. The concentration of the substance in the dosing formulations administered to the animals was confirmed twice during the study. All animals of the parent (P) generation were dosed prior to mating (14 days) and throughout mating. In addition, males received the test item or vehicle after mating up to the day before necropsy (altogether 56 or 57 days). Females were additionally exposed through the gestation period and up to lactation days 12-20, i.e. up to the day before necropsy (altogether for 56 to 66 days). Observations included mortality, clinical signs, body weight, food consumption, mating, pregnancy and delivery process, as well as development of offspring. Estrous cycle was monitored by examining vaginal smears before the treatment for two weeks and for two weeks from the beginning of the treatment period (two weeks pre-mating period) and during the mating period until evidence of mating. The dams were allowed to litter and rear their offspring up to day 13 post-partum. Litters were weighed and offspring were observed for possible abnormalities and were euthanized on post-natal day 13 or shortly thereafter. Blood samples were collected for determination of serum levels of thyroid hormones (T4) from 2-8 pups per litter on post-natal day 4, from all dams and from 4-7 pups per litter at termination on post-partum/post-natal day 13 and from all parent male animals at termination. All parental animals were subjected to gross pathology one day after the last treatment. The body weight, brain weight, weight of the testes, epididymides and prostate and seminal vesicles with coagulating glands as a whole of all adult male animals were determined. Histopathology examination was performed on ovaries, uterus, vagina, testes, epididymides, prostate and seminal vesicles with coagulating gland in the control and high dose groups (male or female). Five dams and the male mating partners were randomly selected from each group to examine further signs of toxicity such as functional observations, hematology, blood coagulation, clinical chemistry, gross necropsy, and organ weighing as well as full histopathology in the control and high dose groups.

There was no mortality in any group during the course of study. Clinical signs of systemic toxicity related to the test item were not detected at any dose level, neither at the daily nor at the detailed weekly clinical observations. At the same intervals, the behavior and physical condition of the animals was not impaired at each dose level (100, 300 or 1000 mg/kg bw/day) during the entire treatment period. Test item related changes of the body weight or body weight gain were not detected. The body weight development was not disturbed and comparable in the control and test item treated groups. The mean daily food consumption was not affected by the test item in male or female animals at all test item groups during the entire study (pre-mating, post-mating, gestation and lactation periods). There were no test item related differences between the control and test item treated groups in the examined parameters of reproductive performance, and in the delivery parameters of dams (100, 300 and 1000 mg/kg bw/day). Clinical pathology examinations (hematology, blood coagulation, clinical chemistry and thyroid hormone levels) did not reveal toxicological relevant alterations related to the test item. Specific macroscopic alterations related to the test item were not found at necropsy. There were no test item related changes in the weights (absolute and relative to body or brain weights) of selected organs in the animals at any dose level.

Histopathological examinations of the selected organs (ovaries, uterus, vagina, testes, epididymides, prostate and seminal vesicles with coagulating gland) did not reveal any test item related changes at the highest dose of 1000 mg/kg bw/day. During full histopathology, there were no changes related to the test item in organs or tissues of selected animals (male or female) at 1000 mg/kg bw/day. No adverse findings on the offspring’s development were detected (mortality, clinical signs and body weight, anogenital distance and nipple retention in male pups, necropsy).

Under the conditions of the present study, the substance did not cause signs of systemic toxicity in parental male and female Hsd.Han: Wistar rats at 100, 300 or 1000 mg/kg bw/day doses administered by oral gavage and the test item did not adversely influence the reproductive performance (gonad function, mating behavior, conception, parturition) in parental male and female rats at the doses of 100, 300 or 1000 mg/kg bw/day. The development of the F1 offspring was not impaired at any dose level from birth to post-natal day 13 after repeated oral administration of dams. Based on these observations the NOAEL were determined as follows:

NOAEL for systemic toxicity of male/female rats: 1000 mg/kg bw/day

NOAEL for reproductive performance of male/female rats: 1000 mg/kg bw/day

NOAEL for F1 Offspring: 1000 mg/kg bw/day

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

The available data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is not considered to be classified for reproductive toxicity under Regulation (EC) No 1272/2008, as amended for the fifteenth time in Regulation (EU) 2020/1182.