Sodium 2-(1-carboxylatoethoxy)-1-methyl-2-oxoethyl laurate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1970-06-12 to 1971-10-13

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1971

Report date:

1971

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The three-generation reproduction study was performed in 1971; there was no test guideline for such test available at that time.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Decanoic acid, 2-(1-carboxyethoxy)-1-methyl-2-oxoethyl ester, sodium salt

Cas Number:

13557-74-9

IUPAC Name:

Decanoic acid, 2-(1-carboxyethoxy)-1-methyl-2-oxoethyl ester, sodium salt

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 12A 5022

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Day 28
- Fasting Period Prior to Study: No
- Housing: Individually housed prior to study
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): once
- Mixing appropriate amounts with (Type of food): The experimental diets were prepared by grinding appropriate amounts of the test material with a small quantity of the basal ration (Purina Laboratory Chow-Meal) in a mortar and pestle and mixing the resultant blend in a Hobart-Dayton mixer with enough basal ration to make a 6000-g batch of the desired concentration. All diets were fortified with USP cod liver oil at a concentration of 1%

Details on mating procedure:

- M/F ratio per cage: 1 M/1 F
- Length of cohabitation: 10 day
- Proof of pregnancy: Not specified

Duration of treatment / exposure:

Day 28 of F0 generation - end of study (weaning of F3 pups)

Frequency of treatment:

Daily

Doses / concentrations

Dose / conc.:

20 000 ppm

Remarks:

Diet containing 2% of sodium stearoyl lactylate.

However, during the first six weeks of the study, rats were fed 60% of these concentrations as they eat more in proportion to body weight than subsequently.

No. of animals per sex per dose:

20

Control animals:

yes

Details on study design:

Original parent rats (F0) were bred twice; the F1A pups were sacrificed at birth and part of each litter was examined either for skeletal abnormalities or for visceral changes. F1B pups were reared to weaning and pups from each litter were taken to constitute the next group of breeders. F1B rats were bred twice, and both F2A and F2B litters were reared to weaning. F2B pups were then distributed into new groups to breed the F3 generations.

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly, Sacrifice

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Mean weekly food intake measured

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: No
- Number of implantations: Yes
- Number of early resorptions: No
- Number of late resorptions: No
- Other: Ovary Weights

Fetal examinations:

- Soft tissue examinations: Yes
- Skeletal examinations: Yes

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:

no effects observed

Description (incidence and severity):

All maternal rats survived their portion of the study and were in good condition throughout.

Dermal irritation (if dermal study):

not examined

Mortality:

no mortality observed

Description (incidence):

All maternal rats survived their portion of the study and were in good condition throughout.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

There were no significant differences in any of the maternal generations.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

There were no significant differences in any of the maternal generations.

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

The gonadal weights between treated and control groups were comparable to one another.

Gross pathological findings:

no effects observed

Description (incidence and severity):

At necropsy no maternal generations showed gross abnormalities.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

None of the histopathological findings were to be ascribed to administration of sodium capryl lactylate, other than the questionable significance of the cortical cyst incidence in the kidneys of the females.

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Maternal developmental toxicity

Number of abortions:

not examined

Pre- and post-implantation loss:

no effects observed

Description (incidence and severity):

Mean testis and ovary weights and mean total uterine implantation sites were respectively comparable among the groups.

Total litter losses by resorption:

not examined

Early or late resorptions:

not examined

Dead fetuses:

no effects observed

Description (incidence and severity):

Stillborn pups examined in the group that received test material were grossly normal.

Changes in pregnancy duration:

no effects observed

Description (incidence and severity):

There was no significant differences observed in the number of gestation days between control and treated dams.

Changes in number of pregnant:

no effects observed

Description (incidence and severity):

No significant difference between groups.

Other effects:

not examined

Effect levels (maternal animals)

Key result

Dose descriptor:

NOAEL

Effect level:

20 000 ppm

Based on:

test mat.

Basis for effect level:

body weight and weight gain

changes in pregnancy duration

clinical signs

dead fetuses

early or late resorptions

effects on pregnancy duration

food consumption and compound intake

gross pathology

histopathology: non-neoplastic

mortality

organ weights and organ / body weight ratios

pre and post implantation loss

Maternal abnormalities

Key result

Abnormalities:

no effects observed

Results (fetuses)

Fetal body weight changes:

not examined

Reduction in number of live offspring:

no effects observed

Description (incidence and severity):

No significant difference was found.

Changes in sex ratio:

no effects observed

Description (incidence and severity):

No significant difference was found.

Changes in litter size and weights:

no effects observed

Description (incidence and severity):

No significant difference was found.

Changes in postnatal survival:

no effects observed

Description (incidence and severity):

There was slightly lower survival at five and twenty-one days which is believed to be because of an intercurrent infection of undetermined nature.

External malformations:

not examined

Skeletal malformations:

effects observed, non-treatment-related

Description (incidence and severity):

Skeletal anomalies seen in test group pups during any of the generations were not in frequencies high enough to be meaningful.

Visceral malformations:

effects observed, non-treatment-related

Description (incidence and severity):

Visceral anomalies seen in test group pups during any of the generations were not in frequencies high enough to be meaningful.

Other effects:

not examined

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Effect level:

20 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

reduction in number of live offspring

changes in sex ratio

changes in postnatal survival

skeletal malformations

visceral malformations

Fetal abnormalities

Key result

Abnormalities:

no effects observed

Overall developmental toxicity

Key result

Developmental effects observed:

no

Any other information on results incl. tables

None of the histopathological observations made in F3 generation were believed to be related to the administration of the test substance sodium capryl lactylate under the conditions of this study other than the questionable significance of the cortical cyst incidence in the kidneys of females.

The full tables of litter data for each generation are below.

F1A Litter Information

Observations	Control	Sodium Capryl Lactylate (2%)
Litters per group	18/20	17/20
Total live pups	207	177
Total Stillborn	1	1
Live pups per litter	11.5	10.4
Mean body weights (g) of live pups	5.53	5.64
Number of male pups	109	90
Number of female pups	98	87

 

F1B Litter Information

Observations	Control	Sodium Capryl Lactylate (2%)
Litters per group	12/20	12/20
Total live pups
Birth	151	125
Day 5	96	62
Weaning	79	53
Total Stillborn	0	1
Live pups per litter	12.6	10.4
Per cent survival at day 5	63.6	49.6
100X weaning survival/ 5 day survival	86.8	93.0
Mean body weights (g) of live pups at
Birth	5.90	6.02
Day 5	9.65	9.18
Weaning	41.5	32.8

 

F2A Litter Information

Observations	Control	Sodium Capryl Lactylate (2%)
Litters per group	19/19	19/20
Total live pups
Birth	221	212
Day 5	127	108
Weaning	81	74
Total Stillborn	1	2
Live pups per litter	11.6	11.2
Per cent survival at day 5	57.5	50.9
100X weaning survival/ 5 day survival	68.6	71.9
Mean body weights (g) of live pups at
Birth	5.96	6.10
Day 5	7.43	7.69
Weaning	33.9	34.0

 

F2B Litter Information

Observations	Control	Sodium Capryl Lactylate (2%)
Litters per group	17/19	20/20
Total live pups
Birth	210	233
Day 5	97	89
Weaning	63	68
Total Stillborn	0	1
Live pups per litter	12.4	11.6
Per cent survival at day 5	46.2	38.2
100X weaning survival/ 5 day survival	72.4	78.2
Mean body weights (g) of live pups at
Birth	5.91	5.91
Day 5	8.34	77.76
Weaning	39.5	32.0

 

F3A Litter Information

Observations	Control	Sodium Capryl Lactylate (2%)
Litters per group	14/20	18/20
Total live pups
Birth	143	199
Day 5	82	164
Weaning	68	147
Total Stillborn	0	1
Live pups per litter	10.2	11.1
Per cent survival at day 5	57.6	82.4
100X weaning survival/ 5 day survival	82.9	89.6
Mean body weights (g) of live pups at
Birth	5.73	5.72
Day 5	8.89	8.57
Weaning	37.5	33.1

 

F3B Litter Information

Observations	Control	Sodium Capryl Lactylate (2%)
Litters per group	16/20	17/20
Total live pups
Birth	167	198
Day 5	115	123
Weaning	101	97
Total Stillborn	1	1
Live pups per litter	11.1	11.6
Per cent survival at day 5	68.9	62.1
100X weaning survival/ 5 day survival	87.8	78.6
Mean body weights (g) of live pups at
Birth	6.03	5.90
Day 5	9.76	8.20
Weaning	36.7	33.4

 

Applicant's summary and conclusion

Conclusions:

There were no differences among control group and those fed sodium capryl lactylate that could be ascribed to treatment. Mortality, body weights, food intake, gross necropsy (gonad weights) and litter data were collected. Sodium capryl lactylate does not adversely effect development in albino rats through three generations.

Executive summary:

A three-generation reproductive study in albino Sprague-Dawley Rats was performed on the test substance sodium capryl lactylate. Mortality, body weights, food intake, gross necropsy (gonad weights) and litter data were collected. There were no differences among control group and those fed sodium capryl lactylate that could be ascribed to treatment. The author noted there was a questionable significance of cortical cyst incidence in the kidneys of females. Sodium capryl lactylate does not adversely affect development in albino rats through three generations.