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Toxicological information

Toxicity to reproduction

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Administrative data

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.

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
No data

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
female

Administration / exposure

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
Doses / concentrations
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

Examinations

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.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

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 / performance (P0)

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.

Effect levels (P0)

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

Results: P1 (second parental generation)

Effect levels (P1)

Remarks on result:
not measured/tested

Results: F1 generation

General toxicity (F1)

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

Details on results (F1)

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.

Effect levels (F1)

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.

Results: F2 generation

Effect levels (F2)

Remarks on result:
not measured/tested

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

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.