TEA-Esterquat

Endpoint summary

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Effects on fertility

Description of key information

NOAEL(reproduction) = 1000 mg/kg bw/d (Reproduction / Developmental Toxicity Screening Test, OECD TG 421, rat m/f, oral: gavage), RL1; GLP; read-across: partially unsaturated TEA-Esterquat

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

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no signs of treatment-related toxicity

Critical effects observed:

no

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no signs of treatment-related toxicity

Reproductive effects observed:

no

Conclusions:

Based on the results obtained in this study, the NOAEL (No Observed Adverse Effect Level) for both general toxicity and reproduction/developmental toxicity was considered to be 1000 mg/kg/day for both males and females.

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

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 experimental data are available for the assessment of reproduction toxicity of the target substance Esterification products of triglycerides C18 unsaturated with triethanolamine, dimethyl sulfate quaternized. However, reliable relevant data are available for the closely related source substance partially unsaturated TEA-Esterquat. A justification for read-across is attached to iuclid section 13.

The toxic effects on Sprague Dawley rats of both sexes were investigated after repeated dosing with the test item partially unsaturated TEA-Esterquat in accordance with OECD Guideline 421 (adopted 29  July 2016). Furthermore, effects of the test item on male and female reproductive performance were examined, i.e. gonadal function, mating behaviour, conception, parturition and early lactation of the offspring. The vehicle was water (was water softened by reverse osmosis. All doses (0, 100, 300 and 1000 mg/kg/day) were administered orally, by gavage at a dose volume of 10mL/kg body weight.

 

Males were treated for 14 days prior to pairing and during pairing with females until the day before necropsy, for a total of 30 days. Females were treated for 14 days prior to pairing, during pairing and throughout the gestation and lactation periods until Day 13 post partum.

The following investigations were performed: body weight, body weight gain, clinical signs, food consumption, macroscopic observations, organ weights and histopathological examination.

In addition the following assessments performed: oestrous cycle evaluation for parental females (2 weeks before start of dosing, during pre-mating and mating phases, prior to necropsy), mating performance, thyroid hormone determination (parental males and pups at Day 13/14 post partum) and collection of litter data.

Clinical signs, anogenital distance, external and/or internal examination were recorded for pups. Thyroid hormone levels and thyroid weight were also determined in 1 pup/sex/group randomly selected at Day 14 post partum.

Routine histopathological examination was performed only in control and high dose groups and it included identification of the stages of the spermatogenic cycle in male animals.

 

1.2 Fate of females

Details of the pregnancy status were as follows:

Groups                                                                                           1          2          3          4

Non-pregnant females                                                                 0          0          0          0

Conceiving 1 - 5 days                                                                  10        10        10        10

No. of females with live pups on Day 13/14 post partum       10         10        10        10

 

1.3 Mortality and clinical signs

No mortality occurred during the study.

Salivation was the most relevant and treatment-related clinical sign recorded during the study. This sign was occasionally noticed in all males and females treated at 1000 mg/kg/day,

starting from the pre-mating phase until sacrifice (end of mating for males and post partum phase for females). Males treated at 300 mg/kg/day also showed salivation, but this sign

appeared later in the study, mostly at the end of the mating phase.

 

1.4 Body weight and body weight gain

No differences in body weight were observed in treated animals of both sexes, when compared to controls and no differences considered treatment-related were observed in body weight gain of treated animals.

 

1.5 Food consumption

Food consumption was unaffected by treatment.

 

1.6 Blood detection of test item

Systemic exposure of pups through the mother milk was also demonstrated by the presence of the physiological degradation product TEA-Core in pups on Day 13post partum, i.e. prior to weaning.  However, quantification was not possible since the detected values of TEA-Core were below the limit of quantification (BLOQ).

 

1.7 Oestrous cycle, reproductive parameters, pairing combination and mating performance

Oestrous cycles, pre-coital interval, copulatory index and fertility index did not show any treatment-related intergroup differences.

 

1.8 Implantation sites, pre-implantation loss data, pre-natal loss data and gestation length of females

Implantation sites, pre-implantation and pre-natal loss and gestation length did not show treatment-related differences.

 

1.9 Litter data and sex ratio of pups

No significant differences in total and live litter size, pup loss, litter weights and mean pup weight were observed among treated and control females at birth and on Days 1, 4 and 13 post partum. Sex ratio did not show any significant differences between groups.

 

1.10 Clinical signs of pups

No signs considered treatment related were seen in pups of treated groups.

 

1.11 Anogenital distance

The statistically significant decrease noted in the ano-genital distance of male and female pups on Day 1 of age in all treated groups was considered incidental and unrelated to treatment, considering that: in both sexes all values were within the range of ERBC historical control data and there was no relation to the dose.

In addition, in females, the decrease observed represents a trend towards feminisation and is not considered an adverse effect (i.e. an increase in AGD of females, suggesting masculinisation); in males, there was no correlations with other findings considered androgen-mediated endpoints (such as areola/nipple retention, cryptorchidism, decreased reproductive organ weights, and malformation incidence).

 

1.12 Thyroid hormones

Parental animals

No differences were recorded between treated and control groups.

Pups - Day 14 post partum

No differences were recorded between treated and control groups.

 

1.13 Necropsy findings in decedent pups, in pups sacrificed on Days 4 and 13/14

post partumand nipple count

No findings were seen at necropsy in decedent pups or in those sacrificed on Days 4 and 13 post partum.

No nipples were observed in male pups on Day 13 post partum.

 

1.14 Pups thyroid weight on Day 13/14post partum

No significant differences were noted in thyroid weight between controls and pups of treated groups.

 

1.15 Terminal body weight and organ weights

No changes attributable to the treatment were observed in terminal body, absolute and relative organ weight of treated animals, when compared to the controls.

 

1.16 Macroscopic observations

No significant differences were noted at post mortem examination in treated animals, when compared to the controls.

 

1.17 Microscopic observations

No treatment-related changes were observed in treated animals, when compared to the controls.

Seminiferous tubules were evaluated with respect to their stage in the spermatogenic cycle and to the integrity of the various cell types within the different stages; regular layering in the germinal epithelium was noted.

 

Conclusion

In conclusion, no signs of treatment-related toxicity were observed at any of the dose levels investigated following treatment with the test item, when administered to rats by oral route at dose levels of 100, 300 and 1000 mg/kg/day. Based on the results of the present study, the NOAEL (No Observed Adverse Effect Level) for general, reproductive and developmental toxicity was considered to be 1000 mg/kg/day for males and females.

There are no data gaps for the endpoint reproduction toxicity. No human data are available. However, there is no reason to believe that these results from rat and rabbits would not be applicable to humans.

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

Based on the available data, Esterification products of triglycerides C18 unsaturated with triethanolamine, dimethyl sulfate quaternized does not need to be classified for toxicity to reproduction according to regulation (EC) 1272/2008. Thus, no labelling is required.