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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
three-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study without detailed documentation for a read-across substance.

Data source

Reference
Reference Type:
publication
Title:
Safety Assessment of Hydrogenated Starch Hydrolysates
Author:
Modderman JP
Year:
1993
Bibliographic source:
Regulatory Toxicology and Pharmacology 18, 80-114 (1993)

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
Deviations:
yes
Remarks:
physio-chemical data not reported; 10 females per group instead of 20, no analytical verification of doses, estrus cycle and sperm parameters not examined, weights of reproductive organs not measured, histopathology not conducted
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): HSH (7:52:41) Lycasin 80/55
- Physical state: Not reported
- Analytical purity: 7.0% sorbitol, 52.5% maltitol, 22.5% tri-to hexosaccharides, and 17.5% higher-order hydrogenated saccharides
- Lot/batch No.: not reported
- Expiration date of the lot/batch: not reported
- Storage condition of test material: not reported

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Iffa Credo, St. Germain, Arbresle, France
- Age at study initiation: 7 weeks
- Weight at study initiation: approximately 50 g
- Fasting period before study: Not reported
- Housing: an environmentally controlled room, makrolon-type cages of dimensions 42 x 30 x 15 cm
- Diet (e.g. ad libitum): stock diet AO3 diet, U.A.R., Billemoisson, Sur-Orge, France
- Water (e.g. ad libitum): drinking water
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 55-60
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: not reported

Administration / exposure

Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
drinking water for animals in the test group was prepared by making 18% (dry weight/volume) solutions of HSH in acidified water
Details on mating procedure:
- M/F ratio per cage: 1/1
- Length of cohabitation: 3 weeks
- Proof of pregnancy: F1 gen: first day of cohabitation was referred to as day 0 of pregnancy; F2 gen: sperm in vaginal smear referred to as day 0 of pregnancy
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility: not reported
- Further matings after two unsuccessful attempts: not reported
- After successful mating each pregnant female was caged (how): not reported
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
Not reported
Duration of treatment / exposure:
started 12 weeks before mating for f1 and from birth for subsequent generations until day 21 of lactation or until week 11 of the F3 generation
Frequency of treatment:
continuous (in diet)
Details on study schedule:
- F1 parental animals not mated until 15 weeks after selected from the F1 litters.
- Selection of parents from F1 generation when pups were 21 days of age.
- Age at mating of the mated animals in the study: 18 weeks
Doses / concentrations
Remarks:
Doses / Concentrations:
18%
Basis:
nominal in water
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: not reported
- Rationale for animal assignment (if not random): random
Positive control:
no

Examinations

Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: end of treatment

BODY WEIGHT: Yes
- Time schedule for examinations: weekly


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: weekly

Oestrous cyclicity (parental animals):
Not reported
Sperm parameters (parental animals):
testes weighed
Litter observations:
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no, on day 21
- If yes, maximum of 20 pups/litter (10/sex/litter as nearly as possible); excess pups were killed and discarded.


PARAMETERS EXAMINED
The following parameters were examined in [F1 / F2 / F3] offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical abnormalities


GROSS EXAMINATION OF DEAD PUPS:
no
Postmortem examinations (parental animals):
SACRIFICE
- Male animals: All surviving animals at 21-days post lactation of the females
- Maternal animals: All surviving animals at 21-days post lactation


GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.


HISTOPATHOLOGY / ORGAN WEIGHTS
The following organs were removed and weighed: hypophysis, brain, thyroid, adrenal capsule, liver, spleen, heart, cecum, and gonads (ovaries and testes)
Postmortem examinations (offspring):
SACRIFICE
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at 21 days of age.
Statistics:
Observations on the F1b, F2b, and F3b generations were averaged and any statistical variation between the control group and the test group were determined using the student's t test
Reproductive indices:
not reported
Offspring viability indices:
not reported

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

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
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not examined
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed

Details on results (P0)

CLINICAL SIGNS AND MORTALITY (PARENTAL ANIMALS)
No clinical symptoms or physiological abnormalities

BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS)
no difference

TEST SUBSTANCE INTAKE (PARENTAL ANIMALS)
no significant effects

REPRODUCTIVE FUNCTION: ESTROUS CYCLE (PARENTAL ANIMALS)
not examined

REPRODUCTIVE FUNCTION: SPERM MEASURES (PARENTAL ANIMALS)
not examined

REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
no significant effects

ORGAN WEIGHTS (PARENTAL ANIMALS)
no significant effects

GROSS PATHOLOGY (PARENTAL ANIMALS)
no significant effects

HISTOPATHOLOGY (PARENTAL ANIMALS)
no significant effects

Effect levels (P0)

Dose descriptor:
NOEL
Effect level:
18 other: %
Sex:
male/female
Basis for effect level:
other: Based on lack of toxic and reproductive effects at 18% HSH
Remarks on result:
other: Generation: general reproductive (migrated information)

Results: F1 generation

General toxicity (F1)

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 examined
Gross pathological findings:
no effects observed
Histopathological findings:
not examined

Details on results (F1)

VIABILITY (OFFSPRING)
The viability rate over the three generation period was high for both groups

CLINICAL SIGNS (OFFSPRING)
No significant effects

BODY WEIGHT (OFFSPRING)
No significant effects

SEXUAL MATURATION (OFFSPRING)
not reported

ORGAN WEIGHTS (OFFSPRING)
not reported

GROSS PATHOLOGY (OFFSPRING)
No significant effects

HISTOPATHOLOGY (OFFSPRING)
not reported

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion