Benzenesulfonic acid, 4-C10-13-sec-alkyl derivs., compds. with 2-propanamine

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Unavailable - study report dated 1971

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

other:

Title:

Unnamed

Year:

1971

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: Prenatal developmental toxicity assay in pregnant rats
- Short description of test conditions: After overnight mating, the rats were randomly allocated to five groups which included one control group and four different treatment groups.LAS was prepared daily as a series of graded aqueous solutions. Animals in all groups were dosed orally at the standard volume of 1.0 mL/100 g. Control animals were dosed in a similar manner with distilled water used as the vehicle. The dams were observed daily for signs of toxicity and weighed on days 1, 3, 6, 10, 14, 17 and 20 of pregnancy. On day 20, the rats were killed by CO2 euthanasia.
- Parameters analysed / observed:Ovaries and uterine contents were examined immediately for number of copora lutea, number of viable young, number of resorption sites, litter weight, and fetal abnormalities.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts

EC Number:

270-115-0

EC Name:

Benzenesulfonic acid, C10-13-alkyl derivs., sodium salts

Cas Number:

68411-30-3

Molecular formula:

Not applicable for UVCB

IUPAC Name:

sodium 4-undecylbenzenesulfonate

Details on test material:

LAS (Na salt) as a slurry containing 64.0% w/v of active ingredient (Lion Oil and Fat Co., Ltd.); average alkyl chain length (based on LAS SIDS Consortium Survey, 2002) = C11.7-12.3.

Test animals

Species:

rat

Strain:

other: Charles River CD strain

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

not specified

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

day 6 to day 15 of pregnancy

Frequency of treatment:

daily

Duration of test:

20 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 other: mg/kg

Doses / concentrations 2

Dose / conc.:

0.2 other: mg/kg

Doses / concentrations 3

Dose / conc.:

2 other: mg/kg

Doses / concentrations 4

Dose / conc.:

300 other: mg/kg

Doses / concentrations 5

Dose / conc.:

600 other: mg/kg

No. of animals per sex per dose:

not specified

Control animals:

yes, concurrent no treatment

Details on study design:

After overnight mating, the rats were randomly allocated to five groups which included one control group and four different treatment groups. LAS was prepared daily as a series of graded aqueous solutions. Animals in all groups were dosed orally at the standard volume of 1.0 mL/100 g. Control animals were dosed in a similar manner with distilled water used as the vehicle. The dams were observed daily for signs of toxicity and weighed on days 1, 3, 6, 10, 14, 17 and 20 of pregnancy. On day 20, the rats were killed by CO2 euthanasia. Their ovaries and uterine contents were examined immediately for number of corpora lutea, number of viable young, number of resorption sites, litter weight, and fetal abnormalities.

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Number of corpora lutea: Yes
- Number of early resorptions: Yes / No / No data
- Number of late resorptions: Yes

Fetal examinations:

- External examinations: Yes

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:

not specified

Dermal irritation (if dermal study):

not examined

Mortality:

not specified

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Change in bodyweight was not affected by treatment at 0.2, 2.0, and 300 mg/kg, but treatment at 600 mg/kg was associated with retarded weight gain and a transient diarrhea following initiation of treatment.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not specified

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:

not examined

Gross pathological findings:

not specified

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not specified

Details on results:

Parent animals were observed daily.Change in bodyweight was not affected by treatment at 0.2, 2.0, and 300 mg/kg, but treatment at 600 mg/kg was associated with retarded weight gain and a transient diarrhea following initiation of treatment

Maternal developmental toxicity

Number of abortions:

not specified

Pre- and post-implantation loss:

not examined

Total litter losses by resorption:

not examined

Early or late resorptions:

no effects observed

Dead fetuses:

not specified

Changes in pregnancy duration:

not specified

Changes in number of pregnant:

no effects observed

Details on maternal toxic effects:

The pregnancy rate was comparable at all dosages.

Effect levels (maternal animals)

Key result

Dose descriptor:

NOAEL

Effect level:

300 other: mg/kg

Based on:

test mat.

Basis for effect level:

body weight and weight gain

Remarks on result:

other: maternal toxicity

Remarks:

retarded weight gain and a transient diarrhea observed at high dose level

Maternal abnormalities

Abnormalities:

no effects observed

Results (fetuses)

Fetal body weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

Mean pup weights were statistically higher at 0.2, 2.0 and 300 mg/kg.

Reduction in number of live offspring:

no effects observed

Changes in sex ratio:

not examined

Changes in litter size and weights:

no effects observed

Changes in postnatal survival:

not examined

External malformations:

no effects observed

Skeletal malformations:

effects observed, treatment-related

Description (incidence and severity):

The distribution of skeletal variants were not statistically significant with the exception of a marginal retardation of sternebral ossification at 600 mg/kg.

Visceral malformations:

no effects observed

Description (incidence and severity):

The incidence of minor visceral anomalies was unaffected by treatment at any dosage.

Details on embryotoxic / teratogenic effects:

- Pregnancy/litter data: The litter parameters assessed included litter size, fetal loss and litter weight. These parameters were not significantly affected by any dosage. Mean pup weights were statistically higher at 0.2, 2.0 and 300 mg/kg.
- Embryonic and fetal development were assessed by the incidence of major malformations. The incidence of minor visceral anomalies was unaffected by treatment at any dosage. The distribution of skeletal variants were not statistically significant with the exception of a marginal retardation of sternebral ossification at 600 mg/kg.

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Effect level:

300 other: mg/kg

Based on:

test mat.

Sex:

male/female

Basis for effect level:

skeletal malformations

Remarks on result:

other: teratogenicity

Remarks:

marginal retardation of sternebral ossification

Fetal abnormalities

Abnormalities:

no effects observed

Overall developmental toxicity

Developmental effects observed:

no

Applicant's summary and conclusion

Conclusions:

Female rats were given LAS orally in distilled water from gestation days 6 to 15 during pregnancy. Some effects such as decreased weight gain and transient diarrhea occurred at the highest dose. Pregnancy rates were comparable at all doses. Litter parameters were not significantly affected at any dose. No significant differences were observed in visceral anomalies or skeletal variants, with the exception of a marginal retardation of sternabral ossification at the highest dose. Based on these results the maternal and developmental NOAELs were therefore determined to 300 mg/kg.

Executive summary:

In a developmental toxicity study LAS was administrated pregnant Charles River CD rats/does in water at dose levels of 0, 0.2, 2, 300 or 600 mg/kg from days 6 through 15 of gestation. The number of animals tested was not specified in the study.

The parent animals were observed daily. Body weight change was not affected by treatment at 0.2, 2.0 and 300 mg/kg, but treatment at 600 mg/kg was associated with delayed weight gain and transient diarrhoea after the start of treatment. Pregnancy rates were comparable at all doses. Litter parameters evaluated were litter size, fetal loss and litter weight. These parameters were not significantly affected by any of the doses. Mean pup weights were statistically higher at 0.2, 2.0 and 300 mg/kg. In addition, embryonic and fetal development was assessed by the incidence of major malformations. The incidence of minor visceral anomalies was not affected by the treatment at any dose. The distribution of skeletal variants was not statistically significant except for a marginal delay in sternal ossification at 600 mg/kg. Based on these observations the maternal and the developmental NOAELs are therefore determined to be 300 mg/kg.