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Key value for chemical safety assessment

Effects on fertility

Description of key information

The key information is a resultant of weight of evidence evaluation based on two sources concerning alkyl lactate esters.

Link to relevant study records

Referenceopen allclose all

Endpoint:
one-generation reproductive toxicity
Remarks:
based on generations indicated in Effect levels (migrated information)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study referred in a reliable review article with limited information about test methods and conditions.
Justification for type of information:
Information based on safety assessment of ethyl-hexyl lactate ester.
Qualifier:
no guideline followed
Principles of method if other than guideline:
28-day aerosol inhalation study to evaluate teratogenic potential.
GLP compliance:
yes
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Route of administration:
inhalation: aerosol
Type of inhalation exposure (if applicable):
nose only
Vehicle:
not specified
Details on mating procedure:
Not specified.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
6 h per day
Frequency of treatment:
Daily for 10 days
Details on study schedule:
Applications on days 6–15 of gestation
Remarks:
Doses / Concentrations:
0, 200, or 600 mg/m3
Basis:
nominal conc.
No. of animals per sex per dose:
12 pregnant rats
Control animals:
yes
Parental animals: Observations and examinations:
Clinical signs, maternal body weight, organ weights and feed consumption.
Oestrous cyclicity (parental animals):
Yes
Sperm parameters (parental animals):
Not examined.
Litter observations:
Not specified.
Postmortem examinations (parental animals):
Yes.
Postmortem examinations (offspring):
Yes.
Statistics:
Not specified.
Reproductive indices:
Not specified.
Offspring viability indices:
Yes.
Clinical signs:
no effects observed
Description (incidence and severity):
No deaths; Slight erythema and desquamation
Dermal irritation (if dermal study):
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
No effects on body weights, but significant reduced feed consumption at 600 mg/m3 and a slight decrease at 200 mg/m3.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
No effects on body weights, but significant reduced feed consumption at 600 mg/m3 and a slight decrease at 200 mg/m3.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
not specified
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:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not examined
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed
Description (incidence and severity):
no statistically significant difference between treated and control groups in the number of corpora lutea, implants live and dead fetus, early and late resorptions, implant loss, or in sex ratio.
Dose descriptor:
NOAEL
Effect level:
200 mg/m³ air
Based on:
test mat.
Remarks:
ethyl-hexyl lactate
Sex:
female
Basis for effect level:
body weight and weight gain
food consumption and compound intake
reproductive performance
other: fertility and reproduction
Remarks on result:
not measured/tested
Clinical signs:
no effects observed
Description (incidence and severity):
No significant difference in sex ratio between treatment and controls.
Mortality / viability:
no mortality observed
Description (incidence and severity):
No diferences between treatment and control of live and dead fetus or implant loss.
Body weight and weight changes:
not specified
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings:
not specified
No treatment-related external or visceral findings were noted. Delayed ossification of the frontalis, metatarsals, and hindlimb phalanges was observed in both treatment groups. These effects were regarded as related to maternal stress due to the combination of the nose-only exposure conditions and respiratory tract irritation of 2-ethylhexyl-L-lactate rather than the manifestation of toxicity by the chemical itself.
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
600 mg/m³ air
Based on:
test mat.
Remarks:
ethyl-hexyl lactate
Sex:
male/female
Basis for effect level:
other: No treatment-related external or visceral findings were noted. No effect on sex ratio.
Remarks on result:
other: Delayed ossification of the frontalis, metatarsals and hindlimb phalanges in both treatment groups, but related to stress concentrations due to the combination of nose-only exposure and respiratory tract irritation of 2-ethylhexyl-L- lactate.
Remarks on result:
not measured/tested
Reproductive effects observed:
not specified
Conclusions:
No significant effects were recorded on gestation of pregnant rats exposed by inhalation up to 600 mg/m3 per day. Treatment related effects were recorded on embryonal/fetal development at 200 and 600 mg/m3. However, these were considered to be indirect effects of maternal stress due to irriattion of the respiratory tract.
Endpoint:
one-generation reproductive toxicity
Remarks:
based on generations indicated in Effect levels (migrated information)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study referred in a reliable review article with limited information about test methods and conditions.
Justification for type of information:
Information based on safety assessment of ethyl lactate.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Dermal developmental study
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Route of administration:
dermal
Duration of treatment / exposure:
Not specified
Frequency of treatment:
Daily for 10 days
Details on study schedule:
Applications on days 6–15 of gestation
Remarks:
Doses / Concentrations:
0, 517, 1551, or 3619 mg/kg
Basis:
other: applied percutaneously
No. of animals per sex per dose:
25 pregnant rats
Parental animals: Observations and examinations:
Clinical signs, maternal body weight, organ weights and feed consumption.
Oestrous cyclicity (parental animals):
Not specified.
Sperm parameters (parental animals):
Not examined.
Litter observations:
Not specified.
Postmortem examinations (parental animals):
Yes.
Postmortem examinations (offspring):
Yes.
Statistics:
Not specified.
Reproductive indices:
Not specified.
Offspring viability indices:
Yes.
Clinical signs:
no effects observed
Description (incidence and severity):
No deaths; Slight erythema and desquamation
Dermal irritation (if dermal study):
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No differences in maternal body weight.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No differences in maternal feed consumption were noted.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified
Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not examined
Reproductive performance:
not examined
Dose descriptor:
NOAEL
Effect level:
3 619 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
clinical signs
mortality
dermal irritation
body weight and weight gain
food consumption and compound intake
Clinical signs:
no effects observed
Description (incidence and severity):
No effects were noted on developmental indices, gross external, soft tissue, or skeletal examination.
Mortality / viability:
no mortality observed
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Sexual maturation:
not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings:
not examined
No effects were noted on developmental indices, gross external, soft tissue, or skeletal examination.
Dose descriptor:
NOAEL
Generation:
F1
Effect level:
3 619 mg/kg bw/day (nominal)
Based on:
test mat.
Remarks:
ethyl lactate
Sex:
male/female
Basis for effect level:
other: no data are available on dermal absorption
Reproductive effects observed:
not specified
Conclusions:
No significant effects were recorded on gestation of pregnant rats exposed topically at dosages up to > 3000 mg/kg bw/day, and no effects were recorded on embryonal/fetal development.
Effect on fertility: via oral route
Endpoint conclusion:
no study available
Quality of whole database:
Based on read-across and weighed evidence of studies with lactate analogues and the direct metabolites.
Effect on fertility: via inhalation route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEC
200 mg/m³
Study duration:
subacute
Species:
rat
Quality of whole database:
Not assignable.
Effect on fertility: via dermal route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
3 619 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Not assignable.
Additional information

Justification for selection of Effect on fertility via oral route:
These studies are the most representative of the list of studies used as weighed evidence.

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 weighed evidence data of studies with analogue alkyl lactates and the direct metabolites (fatty alcohols), there is no evidence of potentially adverse effects on reproductive parameters due to exposure to the product containing both long chain alkyl lactates and fatty alcohols. Hence, there is no reason for classification as hazardous for reproduction.

Additional information