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Key value for chemical safety assessment

Effects on fertility

Description of key information

Reproduction/Developmental Toxicity Screening Test (gavage), rat (Sprague-Dawley) m/f (OECD guideline 421, GLP not specified (publication)): NOAEL: 1000 mg/kg bw/day (nominal) (male/female)

Read-across from Alkylpolyglucoside C12-14 fatty alcohol

Link to relevant study records
Reference
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
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
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
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
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
Dose / conc.:
0 mg/kg bw/day
Remarks:
Control group
Dose / conc.:
100 mg/kg bw/day
Dose / conc.:
300 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
No. of animals per sex per dose:
10
Control animals:
yes
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
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Reproductive function: oestrous cycle:
no effects observed
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
Key result
Critical effects observed:
no
Clinical signs:
no effects observed
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
Key result
Critical effects observed:
no
Key result
Reproductive effects observed:
no
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.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

The reproductive toxicity of Alkylpolyglucoside C12-14 fatty alcohol was assessed in 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.

 

The main difference between source and target substance is the alkyl chain distribution. The justification for read-across is given in the target record.

There is supporting information available on toxicity for reproduction of long chain aliphatic alcohols (C6 - C22). Fertility assays did not reveal any adverse reproductive effects. Furthermore, there was no evidence indicative of adverse changes in the reproductive organs in a number of repeated dose studies. Overall, there are no concerns that the category of long chain alcohols might adversely affect fertility. The available data for developmental toxicity for the category long chain alcohols (LCOH) as a whole does not raise any indication of adverse developmental effects including clearly negative developmental toxicity studies based on studies with rats for C5 alcohol, 1-hexanol, C7–C11 alcohols, and 1-octanol (Hellwig and Jäckh, 1997; Klimisch and Hellwig,1995) (from Veenstra et al. 2009).

 

Taking this supporting information into account, the NOAEL of 1000 mg/kg bw/day as derived for the source substance in a reproduction/developmental screening test in rats can be considered to represent a worst case.

  

Although, it must be noted that a reproductive/developmental toxicity screening study alone is not suitable to exclude for sure the presence of toxic effects to reproduction if the result is negative, together with the results of the subchronic toxicity investigations (no effects on male or female reproductive organs), it can be concluded that alkyl polyglycosides are substances of no concern with regard to toxicity to reproduction. That conclusion is further supported by the common metabolic fate, resulting in the formation of the physiologically occurring metabolites sugar and fatty acids, which are also part of our daily nutrition and of no toxicological concern.

Therefore, based on the considerations above, it can be concluded that the results of the oral reproduction/developmental screening study conducted in the rat with the source substance are likely to predict the properties of the target substance and are considered as adequate to fulfil the information requirement of Annex IX, 8.7.2. The dose descriptor obtained from the existing reproduction/developmental screening study performed on the source substance is considered as an appropriate starting point for deriving a DNEL.

 

No reproductive toxicity is expected to occur after repeated oral exposure to D-Glucose, reaction products with alcohols C16-18 (even numbered). Thus, the NOAEL is considered to be ≥1000 mg/kg bw/day.

 

Effects on developmental toxicity

Description of key information

Reproduction/Developmental Toxicity Screening Test (gavage), rat (Sprague-Dawley) m/f (OECD guideline 421, GLP not specified (publication)): NOAEL: 1000 mg/kg bw/day (nominal) (male/female)

Read-across from Alkylpolyglucoside C12-14 fatty alcohol

Justification for classification or non-classification

Based on the available relevant and reliable data, D-Glucose, reaction products with alcohols C16-18 (even numbered) does not need to be classified and labelled according to the CLP Regulation (EC) No 1272/2008.

Additional information