Dodecanoic acid, 1-methyl-2-sulfoethyl ester, sodium salt (1:1)

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

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

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium 2-sulphonatoethyl laurate

EC Number:

230-949-8

EC Name:

Sodium 2-sulphonatoethyl laurate

Cas Number:

7381-01-3

Molecular formula:

C14H28O5S.Na

IUPAC Name:

sodium 2-(dodecanoyloxy)ethanesulfonate

Details on test material:

- Name of test material: MILLED SLI (76) (Sodium Lauroyl Isethionate)
- Physical state: Off-white fine powder
- Lot/batch No.: SEAC Sample Number: S2833101
- Storage condition of test material: The test article should be stored at room temperature (20 ± 5 °C) in the original container away from direct sunlight, with desiccant.
Dose formulations were stored in the refrigerator (2 - 8 °C) in sealed glass containers. Homogeneity and stability of the test formulations had been confirmed for 17-days under refrigerated conditions in SEAC study AH070194.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd, Switzerland
- Age at study initiation: 11 weeks
- Weight at study initiation: Males: 291-333 g; Females: 172-207 g;
- Food and water: ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
A standard dose volume of 10 mL/kg body weight with a daily adjustment to the actual body weight was used. Control animals were dosed with the vehicle alone (Milli-Q-water).

Details on mating procedure:

Females were housed with sexually mature males (1:1) in special automatic mating cages i.e. with synchronized timing to initiate the nightly mating period, until evidence of copulation was observed. This system reduced the variation in the copulation times of the different females. The females were removed and housed individually if:
a) The daily vaginal smear was sperm positive, or b) A copulation plug was observed. The day of mating was designated day 0 post coitum.

If a female did not mate during the 14-day pairing period, this female was paired with a male of the same group which had already mated successfully. If mating was not recorded during this additional pairing period of a maximum of 14 days, the female was sacrificed and, if indicated, the reproductive organs examined histopathologically in order to ascertain the reason for the infertility.

Duration of treatment / exposure:

Males were treated over a 15-day pre-pairing period and during the pairing period up to one day before necropsy. Females were treated throughout the pre-pairing, pairing, gestation and lactation period up to weaning on day 21 post partum.

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

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

No. of animals per sex per dose:

12 males and 12 females per dose group

Control animals:

yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Once daily

DETAILED CLINICAL OBSERVATIONS: Yes


BODY WEIGHT: Yes daily


FOOD CONSUMPTION:
Males - weekly during pre-pairing and after pairing periods.

Females - pre-pairing period days 1-8 and 8-15; gestation days 0-7, 7-14 and 14-21 post coitum, and lactation days 1-7 and 7-14 post partum (since pups begin to consume maternal feed on or about lactation day 14, food consumption was not recorded after this day).
No food consumption was recorded during the pairing period.

Oestrous cyclicity (parental animals):

Duration of cycle was recorded

Sperm parameters (parental animals):

not reported

Litter observations:

Litters were examined for litter size, live births, still births and any gross anomalies.
Sex ratio of the pups were recorded on days 0/1, 4 and 21 post partum. Pups were weighed individually on days 0 (if possible, without identification), 1, 4, 7, 14 and 21 post partum.

Postmortem examinations (parental animals):

The testes and epididymides of all parental males were weighed as pairs

HISTOPATHOLOGY
Slides of all organs and tissues collected at terminal sacrifice from the animals of the control and high-dose groups were examined. The same applied to the female, which was terminated in extremis. Special emphasis was made on the stages of spermatogenesis and histopathology of interstitial cell structure.
If test item-related morphologic changes were detected in organs of any high-dose animal, those same organs from the mid- and low-dose group were examined to establish a no-effect level, if possible.
Histological examination of ovaries was carried out on any females that did not give birth. In addition, microscopic examination of the reproductive organs of all infertile males was made, if necessary.

Statistics:

Dunnett test, Steel-test, Fisher's exact test

Results and discussion

Results: P0 (first parental generation)

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

Histopathological findings: non-neoplastic:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive performance:

no effects observed

Effect levels (P0)

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Sex:

male/female

Basis for effect level:

clinical signs

body weight and weight gain

food consumption and compound intake

organ weights and organ / body weight ratios

gross pathology

histopathology: non-neoplastic

reproductive function (oestrous cycle)

reproductive performance

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Details on results (F1)

CLINICAL SIGNS (OFFSPRING)


BODY WEIGHT (OFFSPRING)


SEXUAL MATURATION (OFFSPRING)


ORGAN WEIGHTS (OFFSPRING)


GROSS PATHOLOGY (OFFSPRING)


HISTOPATHOLOGY (OFFSPRING)


OTHER FINDINGS (OFFSPRING)

Effect levels (F1)

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

organ weights and organ / body weight ratios

gross pathology

histopathology: non-neoplastic

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

General tolerability:  All animals survived until scheduled necropsy, except one female at 1000 mg/kg, which died, possibly due to a dosing error.

Food consumption and bodyweight:  In males at 300 and 1000 mg/kg, mean food consumption was slightly reduced. Additionally, mean body weights were reduced from the pairing period until the end of the study, whereas no clear dose-dependency was noted. Mean body weight gain was slightly reduced and recovered in the after pairing period at 300 mg/kg but not at 1000 mg/kg.

In females at 1000 mg/kg, mean food consumption was slightly reduced during the treatment period. At 300 mg/kg mean food consumption was only reduced during the second week of the lactation period. As a result, a slight transient reduction of mean body weight gain was noted in the lactation period at both dose levels. Mean body weights were similar in all groups at the end of the study.

Reproductive Data:  The fertility rate was 100% in all groups. At all dose-levels, there were no treatment-related effects on estrous cycle, precoital time, mean duration of gestation, number of corpora lutea and implantations, post-implantation loss, pup survival or litter size from birth through to scheduled sacrifice on day 21 post partum.

Organ Weights:  No significant deviations in mean organ weight of testes and epididymides were recorded which could be attributed to the treatment with the test item, since lower mean absolute weights of epididymides were considered to be in relation with lower body weights and no test item-related histopathological findings were present.

Macroscopical Findings and Histopathological Examinations:  No test item-related histopathologic findings were observed in the reproductive organs of either sex from the parental generation. In particular, the assessment of the integrity of the spermatogenetic cycle did not provide any evidence of impaired spermatogenesis.

Litter Data:  No abnormal findings were noted for pups at first litter check or during the lactation period. Sex ratios at first litter check and on day 21 post partum were unaffected by treatment with the test item.

Mean pup weights on day 1 post partum and mean pup weight development during the lactation period were unaffected by treatment with the test item.

Applicant's summary and conclusion

Conclusions:

In a study performed to OECD 421 on SCI, the NOAEL was 1000 mg/kg body weight/day.