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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Toxic effect type:
dose-dependent

Effects on fertility

Description of key information

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

Based on the physiological role of both potassium and lactate, potassium-S-lactate is considered not to exert any negative 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 potassium-S-lactate.

Link to relevant study records

Referenceopen allclose all

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
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 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
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 potassium-S-lactate itself. To assess the developmental toxicity of potassium-S-lactate, data from the suitable read-across partners potassium chloride and 2-ethylhexyl lactate were used.

In a developmental toxicity study, female CD-1 mice were orally exposed to potassium chloride at doses up to 235 mg/kg bw/d (corresponding to 404 mg/kg bw/d potassium-S-lactate) and female Wistar rats were orally exposed to doses up to 310 mg/kg bw/d (corresponding to 533 mg/kg bw/day potassium-s-lactate) between gestation day 6 and 15. No adverse effects were observed.

In another developmental toxicity study (OECD 414), 2-ethylhexyl lactate was administered daily to female Wistar rats via inhalation at concentration levels up to 600 mg/m³ from day 6 through day 15 of gestation in sessions of six hours. Similarly, no treatment-related adverse effects were observed.

Link to relevant study records

Referenceopen allclose all

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:
not specified
Description (incidence and severity):
Results not further specified
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Description (incidence):
No mortality occurred
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Description (incidence and severity):
Results not further specified
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
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
no effects observed
Description (incidence and severity):
No adverse effects observed
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
The administration of up to 310 mg/kg bw of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on maternal survival.
Number of abortions:
no effects observed
Description (incidence and severity):
No abortion occured in any pregnant female rat.
Pre- and post-implantation loss:
not examined
Total litter losses by resorption:
no effects observed
Description (incidence and severity):
There were no notable effects on resorptions after dosing with potassium chlloride when compared with the controls.
Early or late resorptions:
not examined
Dead fetuses:
no effects observed
Description (incidence and severity):
There were no notable effects on dead fetuses after dosing with potassium chloride when compared with the controls.
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
no effects observed
Description (incidence and severity):
There were no notable effects on the number of pregant females after dosing with potassium chloride when compared with the controls.
Other effects:
no effects observed
Description (incidence and severity):
There were no notable effects on the number of corpora lutea after dosing with potassium chloride when compared with the controls.
Details on maternal toxic effects:
The administration of up to 310 mg/kg bw of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.
Key result
Dose descriptor:
NOAEL
Effect level:
> 310 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: no adverse effects observed at the highest dose tested
Abnormalities:
no effects observed
Fetal body weight changes:
no effects observed
Description (incidence and severity):
There were no notable effects on fetal body weight after dosing with potassium chloride when compared with the controls.
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
There were no notable effects on live fetuses after dosing with potassium chloride when compared with the controls.
Changes in sex ratio:
no effects observed
Description (incidence and severity):
There were no notable effects on sex ratio after dosing with potassium chloride when compared with the controls.
Changes in litter size and weights:
no effects observed
Description (incidence and severity):
There were no notable effects on litter size after dosing with potassium chloride when compared with the controls.
Changes in postnatal survival:
not examined
External malformations:
no effects observed
Description (incidence and severity):
There were no notable effects on external malformations after dosing with potassium chloride when compared with the controls.
Skeletal malformations:
no effects observed
Description (incidence and severity):
There were no notable effects on skelatal malformations after dosing with potassium chloride when compared with the controls.
Visceral malformations:
no effects observed
Description (incidence and severity):
There were no notable effects on visceral malformations after dosing with potassium chloride when compared with the controls.
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
The administration of up to 310 mg/kg bw of the test material to pregnant rats for 10 consecutive days had no clearly discernible effect on fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occuring spontaneously in the sham-treated controls.
Key result
Dose descriptor:
NOAEL
Effect level:
> 310 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effects observed at the highest dose tested
Abnormalities:
no effects observed
Developmental effects observed:
no
Conclusions:
In this study conducted similar to OECD Guideline 414, oral administration of potassium chloride given once a day to Wistar rat dams from Day 6 to 15 of gestation was well tolerated of up to 310 mg/kg/day. As no adverse results were observed in any examined parameter, the NOAEL for reproductive/developmental and maternal toxicity is considered to be 310 mg/kg bw/day.
Executive summary:

In a developmental toxicity study performed similar to OECD 414, potassium chloride was administered to groups of 20-23 pregnant adult female Wistar rats/dose by gavage at dose levels of 0, 3.1, 14.4, 66.8 and 310.0 mg/kg bw/day from day 6 through day 15 of gestation. The animals were sacrificed on gestation day 20.

No treatment-related effects were seen in maternal or offspring survival. Regarding maternal toxicity, no effects were seen in the total number of corpora lutea, implant sites, resorptions, soft tissue observations or live foetuses. Regarding the foetuses, no effects were noticed in sex ratio and average foetus weight. In addition, no differences were seen in either soft or skeletal examinations. As no adverse results were observed in any examined parameter, the NOAEL for reproductive/developmental and maternal toxicity is considered to be 310 mg/kg bw/day (equals 533 mg/kg bw/day)

The developmental toxicity study in the rat is classified acceptable and satisfies the guideline requirement for a developmental toxicity study (according to OECD 414) in rats.

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 read-across report attached to IUCLID section 13.

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
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
Mice were used instead of rats as recommended in the OECD 414 guideline
GLP compliance:
no
Limit test:
no
Specific details on test material used for the study:
- Appearance/state: Fine white crystalline material
- Batch No.: FDA 73-78
Species:
mouse
Strain:
CD-1
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: virgin adult female and young adult males
- Weight at study initiation: 28 - 30 g
- Housing: Anmals were group-housed in disposable plastic cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum, fresh tap water

ENVIRONMENTAL CONDITIONS
- Temperature: controlled, 72 - 98 °F
- Humidity (%): 40 - 76
Route of administration:
oral: gavage
Details on mating procedure:
- Impregnation procedure: cohoused, one male was not permitted to impregnate more than one female per group
- Proof of pregnancy: Observation of vaginal plug referred to as day 0 of pregnancy
Duration of treatment / exposure:
Females were dosed beginning on day 6 and continuing through day 15 of gestation.
Frequency of treatment:
daily
Duration of test:
Until gestation day 17 all dams were subjected to Caesarean section
Dose / conc.:
0 mg/kg bw/day (nominal)
Remarks:
Control
Dose / conc.:
2.35 mg/kg bw/day
Dose / conc.:
10.9 mg/kg bw/day
Dose / conc.:
50.6 mg/kg bw/day
Dose / conc.:
235 mg/kg bw/day
No. of animals per sex per dose:
25-30 females per dose group were mated
Control animals:
yes, concurrent vehicle
Details on study design:
Beginning on day 6 and continuing daily through day 15 of gestation, the females were dosed with 0, 2.35,10.9, 50.6 and 235 mg/kg bw/day potasium chloride by oral intubations. The controls were sham treated with the vehicle. On gestation day 17, all dams were subjected to Caesarean Section under surgical anesthesia.
Maternal examinations:
Body weights were recorded on days 0, 6, 11, 15 and 17 of gestation. All animals were observed daily for appearance and behavior with particular attention to food consumption and weight. The urogenital tract of each dam was examined in detail for anatomical normality.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes, sex ratio, number of corpora lutea, implantation sites, resorption sites and survival (live and dead fetuses) were examined.
Fetal examinations:
- External examinations: Yes, all per litter were examined grossly for the presence of external congenital abnormalities
- Soft tissue examinations: Yes, one-third of the fetuses of each litter underwent detailed visceral examinations employing the Wilson technique
- Skeletal examinations: Yes, the remaining two-thirds were cleared in potassium hydroxide, stained with alizarin red S dye and examined for skeletal defects.

In addition, body weights of fetuses were recorded.
Statistics:
No data
Indices:
Sex ratio, number of corpora lutea, implantation sites, resorption sites and survival, live and dead fetuses
Historical control data:
No data
Clinical signs:
not specified
Description (incidence and severity):
Results not further specified
Dermal irritation (if dermal study):
not examined
Mortality:
no mortality observed
Description (incidence):
No mortality occurred
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No effects on body weight were observed in comparison to the untreated control.
Food consumption and compound intake (if feeding study):
not specified
Description (incidence and severity):
Results not further specified
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
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 specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
No adverse effects observed during gross necrosy in comparison to the untreated control
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
The administration of up to 235 mg/kg bw/day of the test material to pregnant mice for 10 consecutive days had no clearly discernible effect on maternal survival.
Number of abortions:
no effects observed
Description (incidence and severity):
No abortion occured in any pregnant female mouse.
Pre- and post-implantation loss:
not examined
Total litter losses by resorption:
no effects observed
Description (incidence and severity):
There were no notable effects on resorptions after dosing with potassium chloride when compared with the controls.
Early or late resorptions:
not examined
Dead fetuses:
no effects observed
Description (incidence and severity):
There were no notable effects on dead fetuses after dosing with potassium chloride when compared with the controls.
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
no effects observed
Description (incidence and severity):
There were no notable effects on the number of pregant females after dosing with potassium chloride when compared with the controls.
Other effects:
no effects observed
Description (incidence and severity):
There were no notable effects on the number of corpora lutea after dosing with potassium chloride when compared with the controls.
Details on maternal toxic effects:
The administration of up to 235 mg/kg bw of the test material to pregnant mice for 10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival.
Key result
Dose descriptor:
NOAEL
Effect level:
> 235 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: no adverse effects observed at the highest dose tested
Abnormalities:
no effects observed
Fetal body weight changes:
no effects observed
Description (incidence and severity):
There were no notable effects on fetal body weight after dosing with potassium chloride when compared with the controls.
Reduction in number of live offspring:
no effects observed
Description (incidence and severity):
There were no notable effects on live fetuses after dosing with potassium chloride when compared with the controls.
Changes in sex ratio:
no effects observed
Description (incidence and severity):
There were no notable effects on sex ratio after dosing with potassium chloride when compared with the controls.
Changes in litter size and weights:
no effects observed
Description (incidence and severity):
There were no notable effects on litter size after dosing with potassium chloride when compared with the controls.
Changes in postnatal survival:
not examined
External malformations:
no effects observed
Description (incidence and severity):
There were no notable effects on external malformations after dosing with potassium chloride when compared with the controls.
Skeletal malformations:
no effects observed
Description (incidence and severity):
There were no notable effects on skelatal malformations after dosing with potassium chloride when compared with the controls.
Visceral malformations:
effects observed, non-treatment-related
Description (incidence and severity):
There were no notable effects on visceral malformations after dosing with potassium chloride when compared with the controls.
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
The administration of up to 235 mg/kg bw/day of the test material to pregnant mice for 10 consecutive days had no clearly discernible effect on fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occuring spontaneously in the sham-treated controls.
Key result
Dose descriptor:
NOAEL
Effect level:
> 235 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effects observed at the highest dose tested
Abnormalities:
no effects observed
Developmental effects observed:
no
Conclusions:
In this study conducted similar to OECD Guideline 414, oral administration of potassium chloride given once a day to CD-1 mouse dams from Day 6 to 15 of gestation was well tolerated of up to 250 mg/kg bw/day. As no adverse results were observed in any examined parameter, the NOAEL for reproductive/developmental and maternal toxicity is considered to be greater than 250 mg/kg bw/day.
Executive summary:

In a developmental toxicity study performed similar to OECD 414, potassium chloride was administered to groups of 20-24 pregnant adult female CD-1 mouse/dose by gavage at dose levels of 0, 2.35, 10.9, 50.6 and 235 mg/kg bw/day from day 6 through day 15 of gestation. The animals were sacrificed on gestation day 17.

No treatment-related effects were seen in maternal or offspring survival. Regarding maternal toxicity, no effects were seen in the total number of corpora lutea, implant sites, resorptions, soft tissue observations or live foetuses. Regarding the foetuses, no effects were noticed in sex ratio and average foetus weight. In addition, no differences were seen in either soft or skeletal examinations. As no adverse results were observed in any examined parameter, the NOAEL for reproductive/developmental and maternal toxicity is considered to be greater than 250 mg/kg bw/day (equals 404 mg/kg bw/day potassium-S-lactate)

The developmental toxicity study in the mice is classified acceptable and satisfies the guideline requirement for a developmental toxicity study (according to OECD 414) in mice.

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 read-across report attached to IUCLID section 13.
Reason / purpose for cross-reference:
read-across source
Maternal examinations:


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Each mated female was observed daily from gestation day 0 and, if necessary, handled to appraise its physical condition. Signs of ill health and reaction to treatment as well as mortality were recorded.

BODY WEIGHT: Yes
- Time schedule for examinations: Body weights of the mated female rats were recorded on gestation days 0, 6, 10, 15 and 21.

FOOD CONSUMPTION: Yes
- Food consumption of mated females was measured for each animal individually by weighing the feeders on days 0, 6, 10, 15 and 21 of gestation.

WATER CONSUMPTION: No

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21; gross abnormalities were examined
Clinical signs:
effects observed, non-treatment-related
Description (incidence and severity):
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.
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:
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.
Dose descriptor:
NOAEC
Remarks:
maternal toxicity
Effect level:
600 mg/kg bw/day (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.
Dose descriptor:
NOAEC
Remarks:
developmental toxicity
Effect level:
600 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: No differences between foetuses from treated and control dams, except slightly retarded ossification in treated foetuses. This effect was considered to be related to the stress conditions.
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:
not examined
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:
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:
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).

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 study available
Additional information

No developmental toxicity data is available for the target substance potassium-S-lactate. Due to complete dissociation of potassium-S-lactate into K+ ions and lactate under aqueous and/or physiological conditions, the toxicology of potassium-S-lactate can be understood in terms of effects of the dissociation products. The potassium moiety of potassium-S-lactate is considered to be devoid of any reproductive/developmental properties, based on the physiological role of potassium ions: Potassium 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 potassium (thus also potassium-S-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 potassium chloride and from 2-ethylhexyl lactate was used to assess the potential of potassium-S-lactate to induce reproductive/developmental effects. For justification of the read-across approach please refer to IUCLID section 13.

No treatment-related effects on developmental or maternal parameters were detected in a developmental toxicity study (OECD 414) in rats after inhalation of 2-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 a developmental toxicity study, female CD-1 mice were orally exposed to potassium chloride at doses up to 235 mg/kg bw/d (corresponding to 404 mg/kg bw/day potassium-S-lactate) and female Wistar rats were orally exposed to doses up to 310 mg/kg bw/d (corresponding to 533 mg/kg bw/day potassium-s-lactate) between gestation day 6 and 15. No adverse effects were observed.

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 potassium-S-lactate.

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 potassium-S-lactate.

Additional information