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

Toxicity to reproduction

Administrative data

Endpoint:

three-generation reproductive 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 available

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

Limit test:

no

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 species / strain selection:

albino

Sex:

male/female

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:

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

Details on study schedule:

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.

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

Positive control:

none

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly, Time of sacrifice

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

Oestrous cyclicity (parental animals):

Not mentioned

Sperm parameters (parental animals):

Not mentioned

Litter observations:

PARAMETERS EXAMINED
The following parameters were examined in all offspring:
number and sex of pups, stillbirths, live births, presence of gross anomalies, weight gain

GROSS EXAMINATION OF DEAD PUPS:
Yes

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: All surviving animals after offspring weaned.
- Maternal animals: All surviving animals after offspring weaned.

GROSS NECROPSY
- Gross necropsy consisted of gonad weights and litter data.

HISTOPATHOLOGY / ORGAN WEIGHTS
Gonad weights

Postmortem examinations (offspring):

GROSS NECROPSY
- Gross necropsy consisted of gonad weights and litter data.

HISTOPATHOLOGY / ORGAN WEIGHTS
- Gonad weights (i.e. testes in males and ovary in females) in all parent and foetal generations
- Heart, liver and kidney weights of F3 generations (occurred two days after weaning of F3 pups)
- Histopathology of F3 generations

Statistics:

not specified

Reproductive indices:

Testis weights in males
Ovary weights and implantation sites in females
Days of gestation

Offspring viability indices:

Numbe rof live/dead pups per litter

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Description (incidence and severity):

All P0 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 P0 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):

At 19-20 weeks of study the treated P0 rats of either sex weighed 94-99% as much as the controls.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

The mean food consumption paralleled body weights.

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

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Description (incidence and severity):

The uterine implantation sites between treated and control female rats were comparable to one another. There was no significant differences observed in the number of gestation days between control (range of 21-22 days) and treated (range of 21 to 24 days) dams.

Effect levels (P0)

Dose descriptor:

NOEL

Effect level:

20 000 ppm

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

food consumption and compound intake

organ weights and organ / body weight ratios

gross pathology

reproductive performance

Target system / organ toxicity (P0)

Critical effects observed:

no

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:

no effects observed

Description (incidence and severity):

All P1 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 P1 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):

At week 22 the males and females receiving the material in the diet weighed 91 and 103 per cent as much, respectively, as the controls.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Food consumptions figures for the two groups were closely similar throughout the experiment.

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 the P1 parents showed no gross abnormalities.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

not examined

Reproductive performance:

no effects observed

Description (incidence and severity):

Mean testis and ovary weights and mean total uterine implantation sites were respectively comparable among the groups. No meaningful discrepancies between total numbers of implantation sites and total numbers of pups per dam were found.

Effect levels (P1)

Key result

Dose descriptor:

NOEL

Effect level:

20 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

food consumption and compound intake

organ weights and organ / body weight ratios

gross pathology

reproductive performance

Target system / organ toxicity (P1)

Key result

Critical effects observed:

no

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Description (incidence and severity):

Slightly lower survival at five and twenty-one days which is believed to be happenstance, and the fact the survival at weaning in this group was somewhat superior to control weanling survival also indicates that compound feeding was not responsible.

Dermal irritation (if dermal study):

not examined

Mortality / viability:

mortality observed, non-treatment-related

Description (incidence and severity):

Slightly lower survival at five and twenty-one days which is believed to be happenstance, and the fact the survival at weaning in this group was somewhat superior to control weanling survival also indicates that compound feeding was not responsible.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

At week 22 the males and females receiving the material in the diet weighed 91 and 103 per cent as much, respectively, as the controls.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Food consumptions figures for the two groups were closely similar throughout the experiment.

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

Sexual maturation:

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 the F1 generation showed no gross abnormalities. Skeletal and visceral anomalies in sacrificed pups were not in frequencies high enough to be meaningful.

Histopathological findings:

not examined

Other effects:

not examined

Developmental neurotoxicity (F1)

Behaviour (functional findings):

not examined

Developmental immunotoxicity (F1)

Developmental immunotoxicity:

not examined

Effect levels (F1)

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

20 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

viability

clinical signs

mortality

body weight and weight gain

food consumption and compound intake

organ weights and organ / body weight ratios

gross pathology

Target system / organ toxicity (F1)

Key result

Critical effects observed:

no

Results: F2 generation

General toxicity (F2)

Clinical signs:

no effects observed

Description (incidence and severity):

The F2 generation rats were in good condition. Slightly lower survival at five and twenty-one days which is believed to be because of an intercurrent infection of undetermined nature.

Dermal irritation (if dermal study):

not examined

Mortality / viability:

mortality observed, non-treatment-related

Description (incidence and severity):

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

Body weight and weight changes:

no effects observed

Description (incidence and severity):

At week 20 the males and females receiving the material in the diet weighed 93 to 99 per cent as much, respectively, as the controls.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

No significant differences were noted for food consumption.

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

Sexual maturation:

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):

No significant differences were shown between control and test rats. Stillborn pups examined in the group that received test material were grossly normal. Pups that died by day 5 and were in condition suitable for examination were also found to be grossly normal.

Histopathological findings:

not examined

Other effects:

not examined

Developmental neurotoxicity (F2)

Behaviour (functional findings):

not examined

Developmental immunotoxicity (F2)

Developmental immunotoxicity:

not examined

Effect levels (F2)

Key result

Dose descriptor:

NOAEL

Generation:

F2

Effect level:

20 000 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

viability

clinical signs

mortality

body weight and weight gain

food consumption and compound intake

organ weights and organ / body weight ratios

gross pathology

Target system / organ toxicity (F2)

Key result

Critical effects observed:

no

Overall reproductive toxicity

Key result

Reproductive effects observed:

no

Any other information on results incl. tables

There were no other significant differences or effects observed for mortality, body weights, food intake, gross necropsy (gonad weights) in either of the P2 or F3 generations.

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. Sodium stearoyl lactylate does not adversely effect reproduction in albino rats through three generations. The author noted there was a questionable significance of cortical cyst incidence in the kidneys of females.

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 F3 females. Sodium capryl lactylate does not adversely effect reproduction in albino rats through three generations.