D-Glucose, reaction products with alcohols C16-18 (even numbered)

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Data source

Reference

Reference Type:

publication

Title:

Investigations on the effects of alkylpolyglucosides on development and fertility

Author:

H. Messinger, W. Aulmann, M. Kleber, W. Koehl

Year:

2007

Bibliographic source:

Food and Chemical Toxicology 45 (2007) 1375-1382

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Version / remarks:

27th July 1995

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Alkylpolyglucosides C12-14 fatty alcohol

IUPAC Name:

Alkylpolyglucosides C12-14 fatty alcohol

Test material form:

not specified

Specific details on test material used for the study:

Limited details on test substance might also be described as D-Glucopyranose, Oligomeric, C10-16 Alkyl Glycosides

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no information
- Age at study initiation: no information
- Weight at study initiation: no information
- Fasting period before study: no information
- Housing: 5 animals per sex per cage
- Diet: ad libitum (commercially available laboratory rodent diet)
- Water: ad libitum
- Acclimation period: no information
ENVIRONMENTAL CONDITIONS
- Temperature: 21°C (+/- 2°C)
- Humidity: 55 % (+/-10 %)
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Details on mating procedure:

- M/F ratio per cage: no information
- Length of cohabitation: nop information
- Proof of pregnancy: vaginal plug / sperm in vaginal smear
- Further matings after two unsuccessful attempts: no information

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Prior to mating, throughout the gestation (22 days) and lactation period until post mortem day 3.

Details on study schedule:

- Age at mating of the mated animals in the study: 14 weeks

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day

Remarks:

Control group

Doses / concentrations 2

Dose / conc.:

100 mg/kg bw/day

Doses / concentrations 3

Dose / conc.:

300 mg/kg bw/day

Doses / concentrations 4

Dose / conc.:

1 000 mg/kg bw/day

No. of animals per sex per dose:

10

Control animals:

yes

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes

BODY WEIGHT: Yes

OTHER: Effects related to reproduction and hormone balance such as estrous cycle, mating performance, pregnancy rates and the number of embryo resorptions are registered. Pup losses are recorded and the filial generation is examined for behavioural abnormalities and external growth abnormalities.

Oestrous cyclicity (parental animals):

Estrous cycle was monitored.

Sperm parameters (parental animals):

Parameters examined in P male parental generations:
testis weight, epididymis weight

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Effect levels (P0)

Key result

Dose descriptor:

NOEL

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

organ weights and organ / body weight ratios

reproductive function (oestrous cycle)

reproductive function (sperm measures)

reproductive performance

Target system / organ toxicity (P0)

Key result

Critical effects observed:

no

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Effect levels (F1)

Key result

Dose descriptor:

NOEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

not specified

Basis for effect level:

clinical signs

Target system / organ toxicity (F1)

Key result

Critical effects observed:

no

Overall reproductive toxicity

Key result

Reproductive effects observed:

no

Applicant's summary and conclusion

Conclusions:

No adverse effects were observed in all test animals at all doses, the highest dose being 1000 mg/kg/d.

Executive summary:

The reproductive toxicity of the substance was assessed in a an OECD 421 reproductive screening study. Sprague-Dawley rats were randomly assigned to four groups the animals of which were administered with the substance by gavage with 0, 100, 300 and 1000 mg/kg/d. Treatment commenced when males and females were approximately 12 weeks of age, 2 weeks before pairing and continuously thereafter, up to the day before sacrifice (study day 53, day 4 post mortem).

No effects indicative of general toxicity are observed in parental animals. Relative and absolute weights of testes, epididymides, and seminal vesicles do not differ between test substance and control animals. A marginal reduction is seen in absolute and relative prostate weights in all treated males compared to the control group. A significant difference is found for the low dose group only and no dosedependency was found. Therefore, this finding is not considered to be substance related. With regard to reproductive parameters, no test substance related symptoms are observed. One female in the mid-dose group and two females in the high-dose group did not mate until day 10 and were mated with another male afterwards. One female in the high dose group did not mate after a period of 20 days. Mean litter weights, mean pup weights, sex ratios and gestation periods are similar among all groups. Some slight variations in pre-birth loss are seen in the high-dose group although no significant differences to the controls is found. Clinical signs do not show treatment related effects on pre-weaning pups nor do necropsy reveal any effects in decedent or Fl pups. There is no difference between treated and control animals as assessed by macroscopic examination. No adverse effects were observed regarding male and female reproductive organs even at the very high dose of 1000 mg/kg bw/day. So a NOEL of 1000 mg/kg/day can be established.