Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study cited by Messinger et al., 2007.

Data source

Reference
Reference Type:
review article or handbook
Title:
Investigations on the effects of alkyl polyglucosides on development and fertility
Author:
Messinger H, Aulmann W, Kleber M and Koehl W
Year:
2007
Bibliographic source:
Food and Chemical Toxicology

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
not specified
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals and environmental conditions:
Rats are housed in individual cages at 19–23 C and 40–66% relative humidity, 12 h per day at artificial light. There are approximately 10–15 air changes per hour. All animals have ad libitum access to feed and drinking water.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
The test substance is administered orally by gavage once daily from day 6 to day 15 of gestation (10 applications). A standard dose volume of 10 ml/kg body weight is used and adjusted to the body weight of day 6 p.c. (post coitum). Control animals receive the vehicle alone (aqua dest.) for the entire test period.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
The test substance is administered from day 6 to day 15 of gestation.
Frequency of treatment:
Daily.
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
100 mg/kg bw/day
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
300 mg/kg bw/day
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
1000 mg/kg bw/day
Basis:
nominal conc.
Control animals:
yes

Examinations

Maternal examinations:
Clinical conditions and reactions to treatment are recorded at least once daily. Body weights are reported for days 0, 6, 16 and 20 of gestation. All surviving females are sacrificed on day 20 of gestation and the foetuses are removed by caesarean section. At necropsy, the females are examined macroscopically and live foetuses are weighted, sexed, and examined for visceral and skeletal abnormalities.
Ovaries and uterine content:
Gross macroscopic examination include all maternal organs with emphasis on the uterus, uterine contents, position of foetuses in the uterus and number of corpora lutea. Number and distribution of intrauterine implantations are classified as live or dead foetuses, late intrauterine deaths (resorptions), early intrauterine deaths (resorption sites).
Fetal examinations:
The foetuses are removed from the uterus, are sexed, weighted individually and examined for gross external abnormalities and placentae are weighted separately. The brains and viscera of half of the foetuses of each litter are examined as well as skeletal abnormalities in the other half of the litter.
Potential alterations of the foetuses are classified according to a published standard (Klimisch et al., 1992): variations, slight and common structural changes occurring regularly in the control population; retardations, structural differences related to a delayed degree of skeletal ossification (transient stages of development); anomaly, slight relatively rare structural changes not obviously detrimental; malformations, severe rare and/or obviously lethal changes.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
Alkyl glucosides (C10–16, n = 1.4) do not effect rats under the given test conditions during pregnancy. No mortalities occurred in the dams during the study, neither in the vehicle control nor in the groups exposed to alkyl glucosides up to 1000 mg/kg/day. The absolute and the corrected body weight and body weight gain are comparable between the groups. No deviation is observed during the treatment period. Gross macroscopic examination of the maternal organs including ovaries and uterus do not reveal any alterations. Maternal body weight gain, placenta and uterus weight is not affected by the treatment.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
act. ingr.
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
In the examination of the ovaries and uterine content the number of corpora lutea, implantation sites, conception rate, pre-implantation loss, post-implantation loss in the treated groups are comparable to those in the control group. Living foetuses, foetal sex ratio, and total embryonic deaths are not statistically different between treatment groups and controls. All foetuses in treated and control groups were alive. No compound-related differences are noted between the mean reproduction data. From the visceral examinations, one total situs inversus was found in the highest dose group which has to be considered as an individual non-dose related finding. All changes are slight and occur in the control population also. Therefore, it can be concluded that there are no differences in the incidences of external, visceral or skeletal malformations or variations between groups. Incidences were also compared to the historical controls obtained in 6 development toxicity studies according to the OECD guideline No. 414 study design using the same strain (Sprague–Dawley CD). The weights of live foetuses exhibit no significant differences on a litter and individual basis, e.g. mean weight between the control group and the treatment groups.

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The dams tolerated the applied dose levels of up to 1000 mg/kg bw/day without any signs of clinical toxicity. Maternal body weight gain was not affected by the treatment. For maternal toxicity, embryo toxicity and teratogenicity, a NOAEL of 1000 mg/kg bw was deduced.
Executive summary:

In an OECD 414, the dams tolerated the applied dose levels of up to 1000 mg/kg bw/day without any signs of clinical toxicity. Maternal body weight gain was not affected by the treatment. For maternal toxicity, embryo toxicity and teratogenicity, a NOAEL of 1000 mg/kg bw was deduced.