Ethyl (S)-2-hydroxypropionate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No data is available for the target substance ethyl (S)-lactate itself, but as ethyl (S)-lactate is rapidly hydrolysed into lactic acid and ethanol in vivo, the requirement for reproduction toxicity shall be addressed based on information for lactic acid and ethanol. As lactic acid is a major and essential species in mammalian primary metabolism, and a ubiquitous ingredient in all kinds of food it is of minor toxicological relevance in comparison to the second dissociation product ethanol. In a two-generation study conducted at doses of up to 20700 mg/kg bw/day, ethanol had no demonstrable effect on fertility in CD1-mice.

Link to relevant study records

Reference

Reference 1

Endpoint:

two-generation reproductive toxicity

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Analytical verification of doses or concentrations:

yes

Frequency of treatment:

ad libitum

Clinical signs:

no effects observed

Description (incidence and severity):

No clinical signs of toxicity were observed in either male or female mice in any dose group during the dose-range finding study. For the main test no data was provided.

Mortality:

mortality observed, non-treatment-related

Description (incidence):

During the 14-day dose range finding study no male or female animals died. In the main test one male died in the control group in week 13. In the low dose one femal died during week 13. In the mid-dose group one female died during week 11 and in the high-dose group one male died during week 1, one male during week 3, one male died during week 11 and one female died during week 16.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

The percent change in body weight was unaffected by treatment for both males, females and the sexes combined during the dose-range finding study. In the main study, body weights at week 13 were 38.4 +/-0.6 g for all dosage groups and 39.6 +/- 0.6 g for the control group. For females 3.4% lower in at 15% ethanol compared with control at week 13.

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

no effects observed

Description (incidence and severity):

Daily water consumption at week 13, 7.0 +/-0.1 g per mouse for controls, 7.1 +/-0.2 g for the 5% dose group, 6.4 +/- 0.2 g for the 10% and 5.3 +/- 0.2g for the 15% dose group

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Endocrine findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Description (incidence and severity):

The fertility index were in the control group 97% (38/39), in the low dose group 100% (19/19), in the mid-dose 100% (19/19) and in the high dose group 94% (15/16).

Key result

Dose descriptor:

NOAEL

Effect level:

15 other: % v/v

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse signs of systemic toxicity observed

Key result

Critical effects observed:

no

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not examined

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Body weights of F1 mice in the 15.0% ETOH group were significantly lower than controls at 21 days of age and at 74 + 10 days of age, indicating reduced rate of growth in pups in the 15% ethanol group surviving to the lactational and postweaning periods.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

no effects observed

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Endocrine findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Absolute left testis/epididymis weight, right epididymis weight, and seminal vesicle weight were significantly depressed (p<0.01 or 0.05) in the 15.0% ETOH-treated males relative to controls. Absolute male liver; kidney/adrenal, right testis, and prostate weight were unaffected by treatment. When F1 male organ weights were adjusted for body weight, liver weight, and kidney/adrenal weight were significantly elevated (p<0.01 or 0.05) over controls in the ETOH-treated group. Adjusted left testis/epididymis, right testis, right epididymis, prostate, and seminal vesicle weights were not significantly different from controls.
For F1 female mice absolute liver weight and kidney/adrenal weight were unaffected. When female organ weights were adjusted for body weight, both liver weight and kidney/adrenal weight in the 15% ETOH group were significantly elevated relative to controls

Gross pathological findings:

not specified

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Description (incidence and severity):

Tissues from the F1 animals were saved in 10% formalin, but were not submitted for histopathology since most of the adverse effects observed in the ETOH-treated group were likely due to generalized toxicity in the F1 animals.

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

effects observed, treatment-related

Description (incidence and severity):

F1 parental animals were necropsied three weeks after the 7-day cohabitation period. Sperm assessment indicated a significant reduction (p<0.01 in sperm motility in the 15.0% ETOH group relative to controls, but no other significant effects were observed in sperm concentration, % abnormal sperm or % tailless sperm.

Reproductive performance:

effects observed, treatment-related

Description (incidence and severity):

Continuous exposure of the F1 mice to 15% ETOH in the drinking water via their mothers (in utero) and from birth to 74 +/- 10 days of age had no statistically significant effect on the proportion of detected matings or number of fertile F1 pairs, although the mating and fertility indices for the F1 generation exposed to 15% ETOH appeared to be reduced compared to indices for the F1 control pairs. Fertility indices in F1 matings were 85% and 65% in the controls and 15% ethanol groups respectively. Mating and fertility for the F1 control pairs, however appeared to be reduced compared to values previously observed for the F0 control pairs. There was no significant difference between the control and 15% ETOH-exposed F1 pairs in the number of live pups per litter, proportion of pups born alive, sex of pups born alive, or absolute live pup weight (males, females, or sexes combined). When live pup weight (males, females or sexes combined) was adjusted for the number of live and dead pups per litter, the 15% ETOH group was significantly below (p<0.05 or 0.01) the controls.

Key result

Dose descriptor:

NOAEL

Effect level:

10 other: % v/v

Based on:

test mat.

Sex:

male/female

Basis for effect level:

organ weights and organ / body weight ratios

reproductive function (sperm measures)

reproductive performance

Critical effects observed:

no

Clinical signs:

not examined

Dermal irritation (if dermal study):

not examined

Mortality / viability:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Pups born in final F1 generation of animals exposed to 15% ethanol pre- and post-natally weighed less than controls at birth and days 21 and 74.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

no effects observed

Description (incidence and severity):

The sex ratio was not influenced by the treatment.

Anogenital distance (AGD):

not examined

Nipple retention in male pups:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Other effects:

not examined

Behaviour (functional findings):

not examined

Developmental immunotoxicity:

not examined

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

10 other: % v/v

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

Critical effects observed:

no

Clinical signs:

not examined

Dermal irritation (if dermal study):

not examined

Mortality / viability:

not examined

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

F2 offspring weighed less as pups than control pups, males, females or both sexes

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

no effects observed

Description (incidence and severity):

No effects on the sex ratio of born F2 pups were noticed.

Anogenital distance (AGD):

not examined

Nipple retention in male pups:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

not examined

Histopathological findings:

not examined

Other effects:

not examined

Behaviour (functional findings):

not examined

Developmental immunotoxicity:

not examined

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

< 15 other: % v/v

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

Critical effects observed:

no

Key result

Reproductive effects observed:

no

Analytical results during the main study:

The analysis of thedrinking water formulations at 6 week intervals indicated they ranged from 99 to 101% of the nominal concentrations.

Conclusions:

In conclusion, ethanol in drinking water at concentrations of up to 15% (equivalent to 20700 mg/kg bw/day) had no demonstrable effect on fertility in this two-generation study.

Executive summary:

In a two-generation study conducted for the National Toxicology Program (NTP) of US EPA, ethanol was administered ad libitum to male and female CD1 mice (40 animals per sex in the control group, 20 animals per sex in the treatment groups) at concentrations of 0%, 5%, 10% and 15% in drinking water (equivalent to 0, 6900, 13800 and 20700 mg/kg bw/day). Animals (P0) were continuously treated for 1 week prior to mating and for a 14-week cohabitation period followed by a 21-day holding period when they were separated and housed individually. Since ethanol exerted no significant effect on the mating and fertility of the P0 breeding pairs,litters of the control and high dose group were randomly selected on day 21 for rearing and were housed by sex in groups of two or three mice and maintained on the same drinking water level of ETOH as their parents. At 74 + 10 days of age, male and female mice from different litters within treatment groups were cohabited for 7 days. The pairs were then separated, and the females allowed to deliver their litters. The parental F1 mice were necropsied three weeks after the 7-day cohabitation period.

Ethanol treatment had no effect on bodyweights and on the proportion of breeding pairs of the P0 generation producing at least 1 litter during the continuous breeding phase or the number of litters per pair. The number of litters produced per pair, the proportion of pups born alive and the sex of pups born alive were also unaffected by exposure to ethanol. Fertility indices were 97, 100, 100 and 94% in the controls and 5%, 10%, 15% ethanol dose groups. In the 15% ethanol group, the number of live pups per litter was reduced.

Body weights of F1 mice in the 15% ethanol group were significantly lower than controls at 21 days of age and at 74 + 10 days of age, indicating reduced rate of growth in pups in the high dose group surviving to the lactational and postweaning periods. Fertility indices in F1 matings were 85% and 65% in the controls and 15% ethanol group respectively. Other reproductive performance indices e.g. gestation index, changes in lactation and changes in oestrous cycles were not studied. In the F1 15% ethanol group (necropsied three weeks after the 7-day cohabitation period) there was a significantly decreased %motile sperm but no changes in sperm concentration, % abnormal sperm or % tailless sperm and there was a significant decrease in testis, epididymis and seminal vesicle weight.

For the F2 generation, there was no significant difference between the control and 15% ethanol exposed F1 pairs in the number of live pups per litter, proportion of pups born alive, sex of pups born alive, or absolute live pup weight (males, females, or sexes combined). When live pup weight (males, females or sexes combined) was adjusted for the number of live and dead pups per litter, the 15% dose group was significantly below (p< 0.05 or 0.01) the controls.

Based on the results the NOAEL parental can be considered to be 15% (20700 mg/kg bw/day) and the NOAEL for the F1 can be considered to be 10% (13800 mg/kg bw/day) and the NOAEL of the F2 offspring must be considered to be lower than 15%. Overall, ethanol in drinking water at concentrations up to 15% (equivalent to 20700 mg/kg bw/day) had no demonstrable effect on fertility in this two-generation study.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Reference 2

Endpoint:

extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because a two- (or multi-) generation reproductive toxicity study is available

other:

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

NTP study of high quality

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 data is available for the target substance ethyl (S)-lactate. The target substance fully hydrolyses into L(+)-lactic acid/lactate and ethanol under aqueous and/or physiological conditions. Therefore, the requirement for reproduction toxicity shall be addressed based on information for lactic acid and ethanol. For more details on the read-across justification, please refer to IUCLID section 13.

Lactic acid is a ubiquitous and essential molecule of life, found in all higher animals and many micro-organisms. It is also found in many food items. This observation is common textbook knowledge hence can be considered as adequately and reliably documented, fulfilling the criteria of REACH Annex XI, section 1.1. Additional experimental evidence in support of the lack of potential of lactic acid (thus also ethyl (S)-lactate) is scientifically not necessary.

The toxicity and toxicokinetics of lactic acid is specifically described in section 7.1 (Sterenborg, 2007). As lactic acid is a major and essential species in mammalian primary metabolism, and a ubiquitous ingredient in all kinds of food it is of minor toxicological relevance in comparison to the second dissociation product ethanol.

Publicly available data from the read-across substance ethanol was used to assess the reproductive toxicity of the target substance.

In a Two-generation reproductive toxicity study, ethanol was administered to CD-1 mice orally via the drinking water at concentrations of 0, 5 10 and 15% v/v (equivalent to 0, 6900, 13800 and 20700 mg/kg bw/day). Based on the results the NOAEL parental can be considered to be 15% (20700 mg/kg bw/day) and the NOAEL for the F1 can be considered to be 10% (13800 mg/kg bw/day) and the NOAEL of the F2 offspring must be considered to be lower than 15%. Overall, ethanol in drinking water at concentrations up to 15% (equivalent to 20700 mg/kg bw/day) had no demonstrable effect on fertility in this two-generation study.

Based on the assessment of the available data, no classification for developmental/reproductive toxicity is warranted for ethyl (S)-lactate.

Effects on developmental toxicity

Description of key information

No study is available elucidating the developmental toxicity potential of ethyl (S)-lactate itself. Thus, available data from the suitable read-across partner ethyl lactate was used to assess the potential of ethyl (S)-lactate to induce developmental effects. For justification of the read-across approach please refer to IUCLID section 13.

Based on assessment of the available data in a weight-of-evidence approach, no classification for developmental toxicity is warranted for the target substance ethyl (S)-lactate.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

For justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reason / purpose for cross-reference:

read-across source

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

see box "Details on results"

Dermal irritation (if dermal study):

effects observed, treatment-related

Description (incidence and severity):

see box "Details on results"

Mortality:

no mortality observed

Description (incidence):

see box "Details on results"

Body weight and weight changes:

no effects observed

Description (incidence and severity):

see box "Details on results"

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

see box "Details on results"

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Endocrine findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

see box "Details on results"

Gross pathological findings:

no effects observed

Description (incidence and severity):

see box "Details on results"

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Number of abortions:

no effects observed

Description (incidence and severity):

see box "Details on results"

Pre- and post-implantation loss:

no effects observed

Description (incidence and severity):

see box "Details on results"

Total litter losses by resorption:

no effects observed

Description (incidence and severity):

see box "Details on results"

Early or late resorptions:

no effects observed

Description (incidence and severity):

see box "Details on results"

Dead fetuses:

no effects observed

Description (incidence and severity):

see box "Details on results"

Changes in pregnancy duration:

no effects observed

Description (incidence and severity):

see box "Details on results"

Changes in number of pregnant:

no effects observed

Description (incidence and severity):

see box "Details on results"

Other effects:

not examined

Details on maternal toxic effects:

No deaths occurred during this study. Of 25 animals assigned to each group, pregnancy occurred in 25, 24, 23 and 25 rats in the 0 (Sham), 517, 1551 and 3619 mg/kg bw/day dosage groups, respectively.
One low dosage group rat was inadvertently sacrificed on day 18 of gestation, reducing the number of low dosage group rats with day 20 of gestation litters from 24 to 23. The high dosage of Ethyl lactate resulted in a biologically important increase (not statistically significant) in the number of rats with slight (grade 1) erythema and slight (grade 1) desquamation, as compared with the sham control group number. These minimal signs of irritation or dehydration generally did not occur until the last one or two days of the dosage period and sometimes persisted until day 20 of gestation. Hyperactivity occurred on two days for one high dosage group rat; this clinical sign may have been interrelated with the minimal erythema and desquamation that also occurred for this rat.
No other skin reactions or clinical observations and no necropsy observations were considered effects of percutaneous administration of the test substance to the dams at dosages as high as 3619 mg/kg bw/day.
There were no dosage-dependent or statistically significant differences in average maternal body weight gains during the dosage period (calculated as days 6 to 16 of gestation). Similar average maternal body weight changes also occurred for the dams in the four dosage groups during the postdosage period.
Average maternal liver weights and liver weight/terminal body weight ratios (%) were unaffected by percutaneous administration of the test substance at dosages as high as 3619 mg/kg bw/day.
There were no biologically important or statistically significant differences in the absolute (g/day) or relative (g/kg/day) maternal feed consumption values during the dosage period (the entire dosage period is calculated as days 6 to 16 of gestation). Similarly, while slightly decreased for the high dosage group rats during the postdosage period (days 16 to 20 of gestation), there were no biologically important or statistically significant differences in absolute or relative maternal feed consumption average values for the four groups.

Key result

Dose descriptor:

NOAEL

Remarks:

maternal toxicity

Effect level:

1 551 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: see Remarks

Dose descriptor:

NOAEL

Remarks:

developmental toxicity

Effect level:

3 619 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

other: no adverse effects observed

Abnormalities:

no effects observed

Fetal body weight changes:

no effects observed

Description (incidence and severity):

see box "Details on results"

Reduction in number of live offspring:

no effects observed

Description (incidence and severity):

see box "Details on results"

Changes in sex ratio:

no effects observed

Description (incidence and severity):

see box "Details on results"

Changes in litter size and weights:

not examined

Anogenital distance of all rodent fetuses:

not examined

Changes in postnatal survival:

not examined

External malformations:

no effects observed

Description (incidence and severity):

see box "Details on results"

Skeletal malformations:

no effects observed

Description (incidence and severity):

see box "Details on results"

Visceral malformations:

no effects observed

Description (incidence and severity):

see box "Details on results"

Other effects:

not examined

Details on embryotoxic / teratogenic effects:

No observation made at Caesarean-sectioning of the dams was attributed to the test substance. Average values for corpora lutea, implantations, litter sizes, live and dead fetuses, and early and late resorptions were comparable in the four dosage groups. Similarly, the averages for fetal sex ratios, body weights and percentage of dead or resorbed conceptuses per litter were biologically comparable among the four groups. There were no statistically significant differences.
Gross external, soft tissue and skeletal examinations of the fetuses did not reveal any malformations or variations that were considered effects of the test substance.

Key result

Dose descriptor:

NOAEL

Effect level:

3 619 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects observed

Abnormalities:

not specified

Developmental effects observed:

no

Conclusions:

In a developmental toxicity study, ethyl lactate was administered to 25 female Crl:CD®(SD)BR presumed pregnant rats /dose applied percutaneously at dose levels of 0, 517, 1551 and 3619 mg/kg bw/day from days 6 through 15 of gestation. Based on the results, the maternal NOAEL is 1551 mg/kg bw/day and the NOAEL for developmental toxicity is 3619 mg/kg bw/day.

Executive summary:

In a developmental toxicity study conducted according to EPA OTS 798.4000, ethyl lactate was administered for six hours/day to 25 female Crl:CD®(SD)BR presumed pregnant rats/dose group percutaneously under occlusive conditions at levels of 0, 517, 1551 and 3619 mg/kg bw/day from day 6 through 15 of gestation. On day 20 of gestation the animals were sacrificed.

Dermal application of ethyl lactate to pregnant rats at the highest dose that could be given (3619 mg/kg bw/day) caused slight erythema and/or desquamation more frequently in comparison to the control group. Hyperactivity occurred on two days for one rat from the high dose group, which is probably related to the slight erythema and desquamation that also occurred for this rat. No other skin reactions or clinical observations and no adverse necropsy findings were observed in the animals. There were no treatment-related effects on mortality, body weight, food consumption and caesarean parameters. Gross external, soft tissue and skeletal examinations of fetuses did not reveal any malformations or variations that were considered adverse.

It is concluded that percutaneous application of ethyl lactate to pregnant rats was minimally toxic to the dams at the highest dosage that could be tested (3619 mg/kg bw/day), and that this maximum dosage did not result in developmental toxicity. Based on the results, the maternal NOAEL is considered to be 1551 mg/kg bw/day, and the developmental NOAEL is considered to be 3619 mg/kg bw/day.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

GLP study

Additional information

No study is available elucidating the developmental toxicity potential of ethyl (S)-lactate itself. Thus, available data from the suitable read-across partner ethyl lactate was used to assess the potential of ethyl (S)-lactate to induce developmental effects. For justification of the read-across approach please refer to IUCLID section 13.

In a developmental toxicity study conducted according to EPA OTS 798.4000, ethyl lactate was administered for six hours/day to 25 female Crl:CD®(SD)BR presumed pregnant rats/dose group percutaneously under occlusive conditions at levels of 0, 517, 1551 and 3619 mg/kg bw/day from day 6 through 15 of gestation. On day 20 of gestation the animals were sacrificed.

Dermal application of ethyl lactate to pregnant rats at the highest dose that could be given (3619 mg/kg bw/day) caused slight erythema and/or desquamation more frequently in comparison to the control group. Hyperactivity occurred on two days for one rat from the high dose group, which is probably related to the slight erythema and desquamation that also occurred for this rat. No other skin reactions or clinical observations and no adverse necropsy findings were observed in the animals. There were no treatment-related effects on mortality, body weight, food consumption and caesarean parameters. Gross external, soft tissue and skeletal examinations of fetuses did not reveal any malformations or variations that were considered adverse.

It is concluded that percutaneous application of ethyl lactate to pregnant rats was minimally toxic to the dams at the highest dosage that could be tested (3619 mg/kg bw/day), and that this maximum dosage did not result in developmental toxicity. Based on the results, the maternal NOAEL is considered to be 1551 mg/kg bw/day, and the developmental NOAEL is considered to be 3619 mg/kg bw/day.

Justification for classification or non-classification

Based on the assessment of the available data in a weight-of-evidence approach and by way of read-across, no classification for developmental/reproductive toxicity is warranted for ethyl (S)-lactate.