(3-methacrylamidopropyl)trimethylammonium chloride

Endpoint summary

Description of key information

Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test; oral (gavage); rat (Sprague Dawley [Crl:CD(SD)BR]), m/f (OECD guideline 422, GLP): NOAEL = 1000 mg/kg bw/d

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

For MAPTAC, a reliable (RL=1), relevant and adequate study is available on repeated dose toxicity:

In a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test according to OECD Guideline 422 (22 March 1996) MAPTAC was administered to 10 Sprague Dawley [Crl:CD(SD)BR] rats/sex/dose orally by gavage at dose levels of 0 (control), 100, 300 and 1000 mg/kg bw/d. Males were treated for a total of 38 days including 2 weeks prior to pairing and continuously thereafter, up to the day before necropsy.

Females were dosed throughout the study including 2 weeks before pairing, thereafter during pairing, gestation and lactation periods until Day 3 post partum.

No mortality occurred in the study. No clinical signs of toxicological significance were reported. No relevant differences in body weights and food consumption were recorded in animals of both sexes compared to the control group, throughout the study.

Observation of animals at removal from the cage and in an open arena (neurotoxicity assessment) did not reveal changes attributable to the test item. Reduction in motor activity and reduced grip strength (first trial only) observed in males of the high dose group were noted at the end of treatment period when compared to controls. Considering that no differences were noted in other correlated neuromotory tests (second trial of grip strength, landing footsplay and rearing measurements in the open arena) this finding was considered incidental.

Haematology and urinanalysis revealed no changes of toxicological significance.

Some changes in clinical chemistry were noted (increase of protein (9%), albumin (7%), phosphorus (12%), calcium (5%) and decrement of chloride (2%) in high dose males; increase of phosphorus (13%) and decrease of glucose (27%) in mid-dose males; decreases of aspartate aminotransferase (up to 23%) and urea (22%) in mid and/or high dose females). However, these changes were of low severity or not dose-related, therefore considered of no toxicological relevance. Bile acids showed a 7-fold increment in high dose males. However, since only 2 animals showed high values and due to the lack of other relevant findings (e.g. liver markers), this alteration was considered of no toxicological significance.

Measurements of oestrus cycle, pre-coital intervals and copulatory index did not show differences between treated and control groups. No significant differences were observed in the number of implantation, corpora lutea, total litter size, pre-implantation loss, pre-birth loss and gestation length between control and treated groups.

A total of 6 females were found not pregnant at necropsy: 2 in the control group, 1 in the low dose group, 1 in the mid-dose group, 2 in the high dose group. The number of females with live pups on Day 4 post partum was: 8 in each of the control and high dose groups, 9 in each of the low and mid-dose groups. Clinical signs of pups were comparable between groups. At necropsy no findings related to treatment were seen in decedent pups and in pups sacrificed on Day 4 post partum.

 

At necropsy, no macroscopic or microscopic treatment-related changes were noted. In addition seminiferous tubules were evaluated with respect to their stage in the spermatogenic cycle and no alterations were noted.

No relevant toxic effects were seen in parental animals up to the highest dose group of 1000 mg/kg bw/d. On the basis of the results obtained in the study, the NOAEL for both, general toxicity and reproduction/developmental toxicity was 1000 mg/kg bw/d (males/females). 

The absence of adverse effects in the high dose group indicates only little likelihood that adverse effects at the same dose levels or effects at lower doses would occur in studies of longer duration (e.g. 90 day study).

The DNEL was derived usingthe default ECHA assessment factor = 6 for extrapolation from subacute to chronic exposure. Thus, a maximum uncertainty for potential effects of study duration was assumed for purposes of calculating a DNEL. The conduct of studies of longer duration is not justified. Thus, also animal welfare is respected.

 

Exposure to humans via the inhalatory route will be unlikely to occur due to the extremely low vapour pressure and the absence of spray applications. In an acute dermal toxicity study on MAPTAC, no clinical signs of systemic toxicity were observed.

Therefore, together with the extraordinarily low toxicity of MAPTAC, the occurrence of critical effects in repeated dose dermal and/or inhalation exposure tests are extremely unlikely.

Hence, for the sake of animal welfare, further testing is not justified.

 

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
OECD guideline 422 study, no deviations, GLP

Justification for classification or non-classification

Based on the available data, MAPTAC does not need to be classified for repeated dose toxicity according to the criteria given in regulation (EC) 1272/2008 or the former European directive on classification and labelling 67/548/EEC. Thus, no labelling is required.