Sodium lactate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No data is available for the target substance Sodium lactate itself. The target substance completely dissociates into Na+ ions and lactate under aqueous and/or physiological conditions. Therefore, the requirement for reproduction toxicity shall/can be addressed based on information for lactic acid and sodium ions. For more details on the read-across justification, please refer to IUCLID section 13.

Based on the physiological role of both sodium and lactate, Sodium lactate is considered not to exert any adverse effects on fertility.

Nevertheless, in repeated dose toxicity and reproductive/developmental toxicity studies conducted with suitable source substances, no adverse effects on reproductive tissues or organs were observed. Thus, in accordance with REACH Annex IX, section 8.7.3, column 1, it is not necessary to conduct an extended one-generation reproductive toxicity study with the target substance Sodium lactate.

Link to relevant study records

Reference

Reference 1

Endpoint:

screening for reproductive / developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because a pre-natal developmental toxicity study is available

Reproductive effects observed:

not specified

Reference 2

Endpoint:

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

Data waiving:

other justification

Justification for data waiving:

the extended one-generation reproductive toxicity study does not need to be conducted because there are no results from available repeated dose toxicity studies that indicate adverse effects on reproductive organs or tissues, or reveal other concerns in relation with reproductive toxicity

other:

Reproductive effects observed:

not specified

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Effects on developmental toxicity

Description of key information

No data is available for the target substance Sodium lactate itself. The target substance completely dissociates into Na+ ions and lactate under aqueous and/or physiological conditions. Therefore, the requirement for reproduction toxicity shall/can be addressed based on information for lactic acid and sodium ions. For more details on the read-across justification, please refer to IUCLID section 13.

Based on the physiological role of both sodium and lactate, Sodium lactate is considered not to exert any adverse effects on developmental toxicity.

Nevertheless, available data from the suitable read-across partner ethylhexyl lactate was used. In this study conducted according to OECD 414, no treatment-related effects on developmental or maternal parameters were detected in rats after inhalation of ethylhexyl lactate. Therefore, it can be stated that no teratogenic effects were observed in this study and the maternal and developmental NOAEC is considered to be 600 mg/m³. 

Link to relevant study records

Reference

Reference 1

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

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

Reason / purpose for cross-reference:

read-across source

Clinical signs:

effects observed, non-treatment-related

Description (incidence and severity):

Abnormalilics seen during exposure were confined to visually increased breathing rate in animals exposed lo 600 mg/m³ during Ihe entire treatment period and occasionally in rats exposed lo 200 mg/m3. One animal of the control group (A 101) lost part of its tail due to a mechanical trauma. Daily clinical observations did not reveal any noticeable differences in the animals' appearance, general condition or behaviour amongst the various groups.

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, non-treatment-related

Description (incidence):

One animal of the low dose group died on day 11 of gestation because it turned around in the inhalation tube and subsequently suffocated. All other females survived until scheduled Caesarian section.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

There were no significant differences in body weight or body weight change between the control group and the groups exposed to the test substance.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

The food consumption of the high dose group was statistically significantly decreased when compared to the control group throughout the exposure period. The food consumption of the 200 mg/m³ was slightly decreased during the exposure period, but increased thereafter.

Food efficiency:

not specified

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

Behaviour (functional findings):

no effects observed

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Description (incidence and severity):

Gross examination at autopsy did not reveal any significant differences of the maternal organs and tissues among the various groups.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

no effects observed

Description (incidence and severity):

Uterus and ovary weights:
Mean reproductive organ weights and net maternal body weight change during gestation were evaluated. No statistically significant differences in gravid and empty uterus weight, ovary weight, carcass weight and the net weight change (body weight gain from day 0 to 21 of gestation minus gravid uterine weight) were observed between the control group and he groups treated to 2-ethylhexyl lactate.

Number of abortions:

no effects observed

Pre- and post-implantation loss:

no effects observed

Description (incidence and severity):

There were no statistically significant differences between the control group and the groups exposed to the test substance in the numbers of corpora lutea, implantations, live and dead foetuses and early and late resorptions nor in pre- and post-implantation loss or in the sex ratio of the foetuses.

Total litter losses by resorption:

no effects observed

Description (incidence and severity):

There were no statistically significant differences between the control group and the groups exposed to the test substance in the numbers of corpora lutea, implantations, live and dead foetuses and early and late resorptions nor in pre- and post-implantation loss or in the sex ratio of the foetuses.

Early or late resorptions:

no effects observed

Description (incidence and severity):

There were no statistically significant differences between the control group and the groups exposed to the test substance in the numbers of corpora lutea, implantations, live and dead foetuses and early and late resorptions nor in pre- and post-implantation loss or in the sex ratio of the foetuses.

Dead fetuses:

no effects observed

Description (incidence and severity):

There were no statistically significant differences between the control group and the groups exposed to the test substance in the numbers of corpora lutea, implantations, live and dead foetuses and early and late resorptions nor in pre- and post-implantation loss or in the sex ratio of the foetuses.

Changes in pregnancy duration:

not examined

Changes in number of pregnant:

no effects observed

Description (incidence and severity):

From the 12 mated female rats per group, 11 of each group were pregnant.

Other effects:

not examined

Details on maternal toxic effects:

Details on maternal toxic effects:
Clinical signs and mortality:
One animal of the low dose group died on day 11 of gestation because it turned around in the inhalation tube and subsequnetly suffocated. Daily clinical observations did not reveal any differences between dose and control group animals.

Maternal body weight and body weight change:
There were no significant differences in body weight or body weight change between the control group and the groups exposed to the test substance.

Food consumption:
The food consumption of the high dose group was statistically significantly decreased when compared to the control group throughout the exposure period. The food consumption of the 200 mg/m³ was slightly decreased during the exposure period, but increased thereafter.

Parental necropsy observations:
Gross examination at autopsy did not reveal any significant differences of the maternal organs and tissues among the various groups.

Uterus and ovary weights:
Mean reproductive organ weights and net maternal body weight change during gestation were evaluated. No statistically significant differences in gravid and empty uterus weight, ovary weight, carcass weight and the net weight change (body weight gain from day 0 to 21 of gestation minus gravid uterine weight) were observed between the control group and the groups treated to 2-ethylhexyl lactate.

Key result

Dose descriptor:

NOAEC

Effect level:

600 mg/m³ air (nominal)

Based on:

test mat.

Basis for effect level:

other: No differences in clinical signs, maternal body weight or body weight change and necropsy seen in treated animals in comparison to control animals.

Key result

Abnormalities:

no effects observed

Fetal body weight changes:

no effects observed

Description (incidence and severity):

See box “Details on embryotoxic / teratogenic effects” below.

Reduction in number of live offspring:

no effects observed

Changes in sex ratio:

no effects observed

Changes in litter size and weights:

effects observed, treatment-related

Description (incidence and severity):

See box “Details on embryotoxic / teratogenic effects” below.

Changes in postnatal survival:

not examined

External malformations:

no effects observed

Description (incidence and severity):

See box “Details on embryotoxic / teratogenic effects” below.

Skeletal malformations:

no effects observed

Description (incidence and severity):

See box “Details on embryotoxic / teratogenic effects” below.

Visceral malformations:

no effects observed

Description (incidence and severity):

See box “Details on embryotoxic / teratogenic effects” below.

Other effects:

not specified

Details on embryotoxic / teratogenic effects:

Details on embryotoxic / teratogenic effects:
Reproduction and litter data at Caesarian section:
From the 12 mated female rats per group, 11 of each group were pregnant.
Reproduction and litter data revealed no treatment-related changes either as evidenced by the absence of statistically significant differences between the
control group and the groups exposed to the test substance in the numbers of corpora lutea, implantations, live and dead foetuses and early and late resorptions nor in pre- and
post-implantation loss or in the sex ratio of the foetuses.

Foetal external observations:
No statistically significant differences were observed for the individual findings. When compared with the control group, the total number of fetal external
observations was slightly albeit statistically significantly increased in the high concentration group. This difference was mainly due to the low number of foetal
observations in the control group: Only one foetus with a small haemorrhage on the head in the control group versus 4 dysmature foetuses from 4 litters (i.e. foetus weight < 75 % of the mean foetal body weight in the control group) and three large foetuses (i.e. foetus weight > 125 % of the mean foetal body weight) plus one foetus with a flexed limb from one litter of the 600 mg/m³ group. Considering the nature of the findings and the low number in the control group, this difference is not considered treatment related.

Findings of the placenta:
Findings of the placenta were limited to two fused placenta in four fetuses of one female control group animal.

Foetal weight and placental weight:
No significant differences in mean foetal body weights were observed between the control group and the groups exposed to the test substance. Mean placental
weight of the 200 mg/m³ group was increased (statistically significantly for both sexes combined). Mean placental weights in of the 600 mg/m³ were comparable to these in the control group.

Visceral examination:
Examination of foetal soft tissues was limited to the control group and the high concentration group.
Visceral malformations:
No visceral malformations were seen in the control group and the high concentration group.
Visceral anomalies:
No visceral variations were observed in the control and the high-concentration group.

Skeletal examinations:
Skeletal examinations were conducted in all groups.
Skeletal malformations:
None of the fetuses showed skeletal malformations
Skeletal anomalies:
Skeletal anomalies were limited to wavy ribs in 3 foetuses out of 2 litters in the high-concentration groups. The incidence in the high-concentration group did not differ significantly from that in the control group.
Skeletal variations:
No statistically significant differences were observed for the individual findings.
Variations in the ossification of the skeletons
When compared with the control group, the 200 and 600 mg/m³ groups showed the following differences: Increase in the number of foetuses and litters with an incompletely ossified frontalis and unossified metatarsals, which was significant in the 200 mg/m³ group. Furthermore, a delay in the ossification of the hind limb phalanges was observed in the 200 and 600 mg/m³ group. The slightly retarded ossification as observed at 200 and 600 mg/m3, was considered to be a minor developmental effect, most attributable to the stress conditions. No teratogenic effects were observed in this study.

Key result

Dose descriptor:

NOAEC

Effect level:

600 mg/m³ air (nominal)

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Key result

Abnormalities:

no effects observed

Developmental effects observed:

no

Gravimetric analysis:

The mean actual concentrations of 2-ethylhexyl lactate in the test atmospheres (and their standard deviations) were 230 (± 16) and 594 (± 48) mg/m³.

Nominal concentration:

The daily mean airflow through the exposure units were 26.5, 55.9, and 70.4 L/min for the control, low, and high concentration level, respectively. The nominal concentrations were 378 and 751 mg/m³, indicating generation efficiencies of 61 and 79 % for the low and high concentration level, respectively.

Particle size measurement:

Particle size measurement showed that almost all particles in the animals' breathing zone were respirable, viz. they were smaller than or equal to 4.2 µm. The mean mass median aerodynamic siameter (MMAD) was 2.7 and 1.7 µm for the low and high exposure level, respectively. The mean geometric standard deviation was 1.5 for the low concentration level and 1.6 for the high concentration level.

Temperature and relative humidity:

The daily mean temperature was 22.7 ± 0.6 °C, 22.6 ± 0.4 °C and 22.6 ± 0.4 °C for the control, low and high concentration level. respectively. The daily relalive humidity was 56 ± 6%, 52 ± 5% and 52 ± 6 %, respectively.

Conclusions:

In conclusion, no treatment-related effects in developmental parameters or maternal parameters were detected in a developmental toxicity study (OECD 414) after inhalation of 2-ethylhexyl lactate, except slightly retarded ossification. This is considered to be a minor developmental effect, most attributable to the stress conditions. Therefore, it can be stated that no teratogenic effects were observed in this study and the maternal and developmental NOAEC is considered to be 600 mg/m³.

Executive summary:

In a developmental toxicity study (OECD 414), 2-ethylhexyl lactate (98.2% purity) was administered to 12 female Wistar rats per dose level in clean air (nose-only exposure for 6 hours/day) at concentration levels of 0, 200 and 600 mg/m³ from day 6 through day 15 of gestation. On day 21 of gestation the animals were sacrificed. There were no treatment-related effects on mortality, clinical signs, body weight or Casarean parameters. Food consumption of the groups was statistically significantly decreased in comparison to the control group animals. As no differences were noticed in body weight change between control and treated animals this effect was classified as not biologically adverse. Based on the results, the maternal NOAEC is considered to be 600 mg/m³. Moreover, no treatment related effects were noted in developmental parameters, except slightly retarded ossification. This is considered to be a minor developmental effect, most attributable to the stress conditions. Thus, the developmental NOAEC is 600 mg/m³. This developmental toxicity study in the rat is classified acceptable and satisfies the guideline requirement for a developmental toxicity study (OPPTS 870.3700; OECD 414) in rat.

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:

developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Species:

rat

Abnormalities:

not specified

Developmental effects observed:

not specified

Reference 3

Endpoint:

developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Species:

rat

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no adverse effect observed

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

No data is available for the target substance Sodium lactate itself. Due to complete dissociation of Sodium lactate into Na+ ions and lactate under aqueous and/or physiological conditions, the toxicology of Sodium lactate can be understood in terms of effects of the dissociation products. The sodium moiety of Sodium lactate is considered to be devoid of any reproductive/developmental properties, based on the physiological role of sodium ions: sodium is an essential bulk element for the human body. 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 supporting the lack of potential developmental and/or reproductive effects of sodium (thus also Sodium lactate) is scientifically not necessary. 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. Reproductive/developmental toxicity is not a relevant endpoint for such a substance since there is no way of lowering exposure below minimum required levels or normal (or even abnormal) internal levels. The toxicity of lactic acid is specifically described in IUCLID section 7.1 (Sterenborg, 2007). Nevertheless, available data from the suitable read-across partner ethylhexyl lactate was used to assess the potential of Sodium lactate to induce reproductive/developmental effects. For justification of the read-across approach please refer to IUCLID section 13. In this developmental toxicity study conducted according to OECD 414, no treatment-related effects on developmental or maternal parameters were detected in rats after inhalation of ethylhexyl lactate. Therefore, it can be stated that no teratogenic effects were observed in this study and the maternal and developmental NOAEC is considered to be 600 mg/m³. 

In conclusion, based on the assessment of the available data in a weight-of-evidence approach, no classification for developmental/reproductive toxicity is warranted for the target substance Sodium lactate.

 

 

Justification for classification or non-classification

Based on the assessment of the available data, no classification for developmental/reproductive toxicity is warranted for Sodium lactate.