D-Glucopyranose, oligomeric, butyl glycoside

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

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: Guideline study with acceptable restrictions. No data on vehicle for gavage. Limited details on test substance and examinations.

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Deviations:

yes

Remarks:

no data on vehicle for gavage; limited details on test substance and examinations

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

other: Hsd: Sprague–Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: (P) 12 weeks
- Fasting period before study:
- Housing: in groups of 5 per sex per cage
- Diet: laboratory rodent diet (Altromin MT pelleted diet, A. Rieper, Bolzano, Italy), ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 10
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

not specified

Details on mating procedure:

- M/F ratio per cage: 1/1
- Length of cohabitation: 13 days
- Proof of pregnancy: vaginal plug

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

(P) Males and females: 2 weeks before pairing and continuously thereafter, up to the day before sacrifice (study Day 53, Day 4 post partum)

Frequency of treatment:

daily, 7 days/week

Remarks:

Doses / Concentrations:
0, 100, 300, 1000 mg/kg bw
Basis:
nominal conc.

No. of animals per sex per dose:

10

Control animals:

yes

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: clinical signs were recorded daily throughout the study.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: all animals were examined on arrival. Examinations of dams and litters took place on Day 4 post partum.

BODY WEIGHT: Yes
- Time schedule for examinations: body weight gain was recorded during the study.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

Oestrous cyclicity (parental animals):

Vaginal smears are taken daily for 14 days prior to pairing and each morning during the pairing period to detect marked anomalies of the estrous cycle.

Sperm parameters (parental animals):

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

Litter observations:

STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no

PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, presence of gross anomalies, weight gain, physical or behavioural abnormalities, other: implantation per litter

GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals on Day 53 (on Day 4 post partum)
- Maternal animals: All surviving animals on Day 53 (on Day 4 post partum)

Postmortem examinations (offspring):

SACRIFICE
- Animals were subjected to postmortem examinations (macroscopic examination).

Statistics:

Mean values and standard deviations of the following parameters were calculated:
- litter weights at birth and sacrifice
- absolute and relative organ weights of testes, epididymis, seminal vesicles and prostate
- pre-coital intervals
- total litter size, sex ratio (%)
- implantation/litter
- gestation period
- pre-birth loss/litter (number and %)

Reproductive indices:

female: copulation or fertility index
males: fertility index

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

not specified

Other effects:

no effects observed

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
No clinical signs were observed during the whole study period.

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
No effects on body weights were noted during the study.

TEST SUBSTANCE INTAKE (PARENTAL ANIMALS)
No effects on food consumption were observed during the experimental period.

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
No effects on estrous cycle were reported.

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
No treatment-related effects on absolute and relative weights of testis and epididymis were observed at any dose level.

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
In males and females, no substance-related effects on fertility index were observed. A slight, but not significant decrease in copulatory index was observed in females receiving the high dose (1000 mg/kg bw/d). 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.

ORGAN WEIGHTS (PARENTAL ANIMALS)
No effects on relative and absolute weights of testis, epididymis, and seminal vesicles were observed between test substance-treated and control animals. A marginal reduction in absolute and relative prostate weights in all treated males compared to the control group was noted. In the low dose group (100 mg/kg bw/d) a significant reduction in the weights of prostate were observed. Due to the absence of dose-dependency, this effect was not considered to be biologically significant.

GROSS PATHOLOGY (PARENTAL ANIMALS)
No substance-related effects were seen at macroscopic examination.

Key result

Dose descriptor:

NOAEL

Remarks:

systemic toxicity

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related effects

Key result

Dose descriptor:

NOAEL

Remarks:

reproductive toxicity

Effect level:

1 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no adverse effects on male and female reproductive organs and performance

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not specified

VIABILITY (OFFSPRING)
No effects on mean litter weights and sex ratios were observed between the F1 generations of treated and control animals. Some slight, but not significant variations in pre-birth loss were seen in the high-dose group compared to controls.

CLINICAL SIGNS (OFFSPRING)
No treatment-related clinical signs were observed in pre-weaning pups.

BODY WEIGHT (OFFSPRING)
No differences in the mean litter weight on Day 0 (birth) and Day 4 (sacrifice) were noted in treated and control groups.

GROSS PATHOLOGY (OFFSPRING)
Necropsy did not reveal any substance-related effects in decedent or F1 pups.

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

ca. 1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: no treatment-related effects

Reproductive effects observed:

not specified

Conclusions:

The test substance had no effect on reproductive performance.

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

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 2) from a reference substance with similar structure and intrinsic properties.

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

There are no data available on the toxicity to reproduction (fertility) of D-Glucopyranose, oligomeric, butyl glycoside. In order to fulfil the standard information requirements set out in Annex IX, 8.7, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances is conducted.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Sections 7.1 and 13).

Data on reprotoxicity is available from the category member D-Glucopyranose, oligomeric, C10-16-alkyl glycosides, which is used for category approach.

In a reproductive/developmental toxicity screening assay according to OECD 421, the test substance was applied to 40 males and 40 females Sprague-Dawley rats prior to mating, throughout the gestation and lactation period until post partum Day 4. Treatment by gavage with 0, 100, 300 and 1000 mg/kg bw/day began 7 days after allocation for both males and females. 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 partum). No effects on the fertility were observed up to the highest dose, thus a NOAEL of 1000 mg/kg bw/day was derived for the test substance (RTC Ltd., 2007).

The lack of major toxicity was further confirmed by a subchronic toxicity study in Sprague Dawley rats that did not show any substance-related systemic toxic effects in either gender up to the limit dose of 1000 mg/kg bw/day (Henkel, 1989).

From the studies presented, there is no indication for any impairment of reproduction, either with regard to the development of the progeny or to the effects on fertility both of the structural and functional level. Therefore, a hazard of reproductive toxicity for D-Glucopyranose, oligomeric, butyl glycoside is not expected to occur, either.

However, it must be noted that a reproductive/developmental toxicity screening study is not suitable to exclude for sure the presence of toxic effects to reproduction if the result is negative. Nevertheless, 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.

Short description of key information:
NOAEL (OECD 421), rat, systemic and reproductive toxicity = 1000 mg/kg bw/day, based on read-across

Justification for selection of Effect on fertility via oral route:
Hazard assessment is conducted by means of read-across based on a category approach. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall assessment of quality, duration and dose descriptor level (refer to the endpoint discussion for further details).

Justification for selection of Effect on fertility via inhalation route:
No study required since the substance has a low vapour pressure and is marketed in liquid form; therefore, human exposure to vapours or dusts is not to be expected.

Justification for selection of Effect on fertility via dermal route:
No study required since data from structurally related substances according to Regulation (EC) No 1907/2006, Annex XI, article 1.5 demonstrate a lack of acute toxicity via the dermal route and negligible dermal absorption through human skin in vitro.

Effects on developmental toxicity

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Justification for selection of Effect on developmental toxicity: via oral route:
Endpoint not required for this tonnage band, but adequate and reliable study for read-across substance based on a category approach available and used for hazard assessment in higher tonnage bands.

Justification for selection of Effect on developmental toxicity: via inhalation route:
No study required since the substance has a low vapour pressure and is marketed in liquid form; therefore, human exposure to vapours or dusts is not to be expected.

Justification for selection of Effect on developmental toxicity: via dermal route:
No study required since data from structurally related substances according to Regulation (EC) No 1907/2006, Annex XI, article 1.5 demonstrate a lack of acute toxicity via the dermal route and negligible dermal absorption through human skin in vitro.

Justification for classification or non-classification

The available data on reproductive and developmental toxicity of a structurally related substance to D-Glucopyranose, oligomeric, butyl glycoside according to the criteria laid down in regulation (EC) No 1907/2006, Annex XI, 1.5 do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC; therefore, D-Glucopyranose, oligomeric, butyl glycoside is not expected to meet the classification criteria, either, and the data is thus conclusive but not sufficient for classification.