Diutan gum

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well reported, GLP-compliant study of close chemical analogue, using method similar to that of relevant OECD guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

Exposure restricted to the period of organogenesis (gestation dates 6-15).

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Gellan gum

EC Number:

275-117-5

EC Name:

Gellan gum

IUPAC Name:

Gellan gum

Details on test material:

Gellan gum (EC 275-117-5): blend of 5 production samples, mean polysaccharide content 58.5% .

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

Adults housed separately in wire mesh bottomed, stainless steel cages (but paired for mating). Fed (powdered diet) and given access to water ad libitum. Animal room held at 21+/-3 degrees C, 50 +/-20% RH with 12 hour light, 12 hour dark cycle.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: test substance mixed in powdered diet

Details on exposure:

Test substance mixed with powdered diet in blender.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Stability and homogeneity of test substance in diet confirmed (pre-test) by results from another study using same substance and techniques. During the test period, samples taken and analysed to confirm concentration.

Details on mating procedure:

Females mated with one male of proven fertility; mating confirmed by presence of spermatozoa in vaginal lavage (designated gestation day 0).

Duration of treatment / exposure:

Days 6-15 of gestation.

Frequency of treatment:

Continuous daily exposure in food.

Duration of test:

Females terminated on gestation day 20.

No. of animals per sex per dose:

25 females mated per group

Control animals:

yes, plain diet

Details on study design:

Females weighed on days 0,6,9,12,15,18,20 of gestation.

Examinations

Maternal examinations:

Daily observations and regular weighing. Detailed gross pathology examinations at necropsy.

Ovaries and uterine content:

Corporal lutea plus early, mid and late resorptions and live or deal foetuses scored. Implantation sites counted in non-pregnant rats (Salewski staining).

Fetal examinations:

All weighed and given detailed external examination (and sex recorded). Half of those in each litter given detailed internal examination then eviscerated and heads removed and placed in Bouin's fluid for later examination: bodies plus all other (eviscerated) foetuses transferred to alcohol for alizarin red staining and skeletal examination.

Statistics:

Maternal data: 1-way anovar then (if F significant) pairwise group comparisons using Student's t test.
Foetal data: Mann-Whitney U test (Student's t test for weights).

Indices:

Pregnancy rate.
Pre- and post- implantation losses.
Incidences of foetal malformations and minor anomalies.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
No evidence of maternal toxicity was seen. Minor gross pathology findings at termination were considered unrelated to treatment. Pregnancy rate was at least 88% in all groups.

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

5 other: % in diet

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

5 other: % in diet

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The incidence of major malformations in test groups was no different from that among controls.
Subcutaneous oedema and accompanying skin changes in 7 foetuses from one litter made the occurrence of minor external/visceral anomalies significantly raised at 3.8%.
Cases of reduced ossification at 2.5% (mainly ribs) and 3.8% (mainly parietal bones) made group values significantly different from controls.
Common skeletal (sternebrae 1-4) variants were significantly increased at 3.8%.
None of the above minor anomalies/variants were seen in rats of the highest treatment group (5% in diet): it was concluded that they were not related to gellan gum exposure.

Effect levels (fetuses)

1

Dose descriptor:

NOAEL

Effect level:

5 other: % in diet

Based on:

test mat.

Basis for effect level:

other: embryotoxicity

2

Dose descriptor:

NOAEL

Effect level:

5 other: % in diet

Based on:

test mat.

Basis for effect level:

other: fetotoxicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Based on reported female bodyweights and food intake figures, rats given 5% gellan gum in diet received approximately 3.9g gellan gum/kg bodyweight/day.

Applicant's summary and conclusion

Conclusions:

Exposure to gellan gum at up to 5% in diet (equivalent to an intake of approximately 3.9 g/kg/day) produced no evidence of maternal toxicity, no treatment-related embryo/foetal toxicity and no evidence of developmental toxicity. Based on the close similarity of chemical composition, it is reasonable to predict that Diutan would show a similar absence of reproductive and developmental toxicity.