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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
<1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: The method used does not meet presently accepted procedures. E.g. the dosing scheme.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1979

Materials and methods

Test guideline
Qualifier:
no guideline available
Version / remarks:
No guideline available at the time of performance.
Principles of method if other than guideline:
Phenoxyacetic acid (and two structurally related compounds) were administered by gavage to pregnant mice on one of gestation days 8-15 (copulation plug day = day 1) or on three consecutive days (7-9, 10-12, or 13-15). Doses were 800-900 mg/kg for single and 250-300 mg/kg/day for multiple treatments. Mortality and fetal weight were determined. Skeletal, visceral or histopathological foetal anomalies and malformations were investigated. Only the part on phenoxyacetic acid is recorded here.
GLP compliance:
not specified
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
SMILES: O=C(O)COc(cccc1)c1
Specific details on test material used for the study:
Phenoxyacetic acid (PA) was obtained from Eastman Kodak, Rochester, New York.

Test animals

Species:
mouse
Strain:
CD-1
Details on test animals and environmental conditions:
Randombred CD-1 albino mice were obtained from the Charles River Breeding Laboratory and given Wayne Lab Blox and water ad libitum.

Administration / exposure

Route of administration:
oral: gavage
Details on exposure:
Phenoxyacetic acid (PA) was suspended in honey and water (1:1). The concentration suspended was calculated on the basis that a 30 gram mouse would be given a volume of 0.25 ml.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
Mated females were detected by the presence of copulation plugs, and the plug day was designated day one of gestation.
Duration of treatment / exposure:
One or three consecutive treatments.
Frequency of treatment:
The test substance was administered at a dose of 800-900 mg/kg of body weight on one of days 8-15 of gestation or at a dose of 250-300 mg/kg of body weight on three consecutive gestation days (7-9, 10-12, or 13-15).
A minimal lethal dose of 1000 mg/kg was established in preliminary trials.
Duration of test:
Until gestation Day 18.
Doses / concentrationsopen allclose all
Dose / conc.:
850 mg/kg bw/day (nominal)
Remarks:
A single dose was 800 to 900 mg/kg bw/d on one of the Days 8 to 15 of gestation.
Dose / conc.:
275 mg/kg bw/day (nominal)
Remarks:
A dose of 250 to 300 mg/kg bw/d was administered on three consecutive days (Days 7 -9; 10-12; or 13-15) of gestation.
No. of animals per sex per dose:
Eight or more litters were produced per treatment day x dose.
Control animals:
yes, concurrent no treatment
yes, concurrent vehicle
Details on study design:
On gestation day 18, treated females were killed by cervical dislocation. Uteri were exposed and examined to determine the numbers of live, dead, and resorbed fetuses. Live fetuses were examined for gross external malformations and weighed. Two fetuses were randomly chosen from each litter, dissected, and examined for visceral abnormalities; their skulls were stored in 70% ethanol and then subjected to free hand sectioning and examination for malformations of the brain, and oral and nasal cavities. Additional fetuses from each litter were selected at random and placed in cold buffered 10% formalin for a later histopathological examination. All other fetuses were stored in 70% ethanol and later eviscerated, stained with alizarin red S and examined for skeletal malformations.

Examinations

Ovaries and uterine content:
On gestation day 18, treated females were killed by cervical dislocation. Uteri were exposed and examined to determine the numbers of live, dead, and resorbed fetuses.
Fetal examinations:
Live fetuses were examined for gross external malformations and weighed. Two fetuses were randomly chosen from each litter, dissected, and examined for visceral abnormalities; their skulls were stored in 70% ethanol and then subjected to free hand sectioning and examination for malformations of the brain, and oral and nasal cavities. Additional fetuses from each litter were selected at random and placed in cold buffered 10% formalin for a later histopathological examination. All other fetuses were stored in 70% ethanol and later eviscerated, stained with alizarin red S and examined for skeletal malformations.
Statistics:
Fetal weights were compared by use of a one-way ANOVA followed by Gabriel's multiple range test. The incidences of deaths and resorptions were compared nonparametrically by the rank sum method of Wilcoxon and Wilcox. Incidences of gross malformations, skeletal malformations, and cleft palates were compared by arcsin transformation of means, followed by a one-way ANOVA and Gabriel's multiple range test, In all cases, statistical analyses were done on a per litter basis.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
not specified
Total litter losses by resorption:
not specified
Early or late resorptions:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
850 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: No effects.
Remarks on result:
other: The dose refers to a single dose on one of the gestation days.
Dose descriptor:
NOAEL
Effect level:
275 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: no effects.
Remarks on result:
other: The dose refers to 3 consecutive doses within the gestation days 7 to 15.

Maternal abnormalities

Abnormalities:
no effects observed

Results (fetuses)

Fetal body weight changes:
effects observed, treatment-related
Description (incidence and severity):
A lower foetal body weight was observed only when dosed at gestation Day 15.
External malformations:
no effects observed
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
no effects observed
Description (incidence and severity):
Histopathological examinations.

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEL
Effect level:
850 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects
Remarks on result:
other: The dose refers to a single dose on one of the gestation days
Dose descriptor:
NOAEL
Effect level:
275 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects
Remarks on result:
other: The dose refers to 3 consecutive doses within the gestation days 7 to 15.

Fetal abnormalities

Abnormalities:
no effects observed

Applicant's summary and conclusion

Conclusions:
No significant skeletal, visceral or histopathological defects of the foetuses were observed.
Executive summary:

Phenoxyacetic acid (and two structurally related compounds) were suspended in a 1:1 solution of honey:water and administered by gavage to pregnant mice on one of gestation days 8-15 (copulation plug day = day 1) or on three consecutive days (7-9, 10-12, or 13-15). Doses were 800-900 mg/kg for single and 250-300 mg/kg/day for multiple treatments. No increased prenatal mortality, and no decreased fetal weight were observed compared to the solvent controls. Low incidences, not gaining significance, of increased cleft palate or other gross malformations were seen in all treatment groups. Significant skeletal, visceral or histopathological defects were not observed.