Sodium 2-(2-dodecyloxyethoxy)ethyl sulphate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

ASSESSMENT OF THE TERATOGENIC POTENTIAL OF SURFACTANTS PART I -- LAS, AS AND CLD

Author:

A.K. PALMER, M.A. READSHAW and A.M. NEUFF

Year:

1975

Bibliographic source:

Toxicology, 3 (1975) 91-106

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Toxicity of Sodium Lauryl Sulphate (as alcohol sulphate) was assessed in New Zealand White rabbit in a one generation study

GLP compliance:

not specified

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium dodecyl sulphate

EC Number:

205-788-1

EC Name:

Sodium dodecyl sulphate

Cas Number:

151-21-3

Molecular formula:

C12H25NaO4S

IUPAC Name:

sodium dodecyl sulfate

Details on test material:

- Name of test material : Sodium Lauryl Sulphate (sodium dodecyl sulphate) or Alcohol sulphate
- Molecular formula : NaC12H25SO4
- Molecular weight : 288.372
- Substance type : Organic
- Physical state : Solid

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: East Anglian Rabbitries, Colchester, England
- Age at study initiation: N/A
- Weight at study initiation: N/A
- Fasting period before study: N/A
- Housing: individually in metal cages equipped with wire mesh floors
- Diet (e.g. ad libitum): rabbits SG-1 diet
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: N/A

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 + 20C
- Humidity (%): N/A
- Air changes (per hr): N/A
- Photoperiod (hrs dark / hrs light): N/A

Administration / exposure

Route of administration:

other: Oral (intubation)

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
For administration Sodium Lauryl Sulphate was prepared daily as a series of graded aqueous solutions so that within study Rabbits in all groups were dosed orally by intragastric intubation at a standard volume. Control animals were dosed with water.

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

- Proof of pregnancy : Observation of coitus in rabbits was considered day 0 of pregnancy

Duration of treatment / exposure:

Day 6 to 18 of pregnancy

Frequency of treatment:

Daily

Duration of test:

13 days

No. of animals per sex per dose:

Control:
13 females
0.2 mg/kg/day:
13 females
etc

Control animals:

yes, concurrent vehicle

Details on study design:

Two dosages were chosen to form the basis for safety evaluation at 0.2 and 2.0 mg/kg/day, As the likely maximum human intake of detergent from ordinary kitchen use has been estimated at 0.14mg/ kg/day these provided factors of 1-2 and 10-20 times the human exposure level. Additionally two further dosages were also investigated 300 and 600 mg/kg/day. At these dosages (which from other toxicity data were considered likely to impair maternal economy) it was hoped to provoke some obvious adverse effects, the pattern of which would help in assessing the relevance of any marginal differences that might occur at the lower dosages.

Examinations

Maternal examinations:

All animals were observed daily for signs of malreaction and were weighed regularly throughout gestation. All animals that died, and survivors at termination, were dissected and examined for macroscopic changes.

Ovaries and uterine content:

At termination day 29, rabbits were killed by cervical dislocation. The uteri were immediately dissected and the contents examined to determine the numbers of {a) implantations, (b) viable young, (c) embryonic deaths (abortion or resorptions sites). Ovaries of rabbits were examined and the number of corpora lutea counted.

Fetal examinations:

Viable young were weighed and carefully examined for external abnormalities. The foetuses were immediately dissected and examined for abnormalities of the internal organs; sex was determined by gonadal inspection, and the carcasses preserved in alcohol for subsequent clearing, alizarin staining and skeletal examination.

Statistics:

Differences in mean values were statistically analysed by non-parametric methods (Wilcoxon test) since litter values rarely, if ever, follow a normal (Gaussian) distribution; in all analyses the litter was considered as the basic sample unit.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Diarrhea, anorexia, and cachexia were observed in rabbit prior to death. Weight loss was observed in higher dose group. Increased fetal loss and reduced litter size total litter loss (abortion and/or total resorption) was observed which occur as a secondary consequence of the primary effect on the mother.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

> 600 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Remarks on result:

other: not specified

Maternal abnormalities

Abnormalities:

not specified

Localisation:

not specified

Description (incidence and severity):

not specified

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
The incidence of major malformations was unaffected. The incidence of minor visceral and skeletal anomalies was also unaffected. The distribution of extra ribbed pups (skeletal variant) was not unduly affected even at maternally toxic dosages since the only notable deviations from control values were a non-significant higher incidence among rabbits at 300 mg/kg. At non-maternally toxic dosages the only deviations from control values were the significantly higher incidence of extra ribbed rabbit pups associated with Sodium Lauryl Sulphate at 2.0 mg/kg.

Effect levels (fetuses)

Dose descriptor:

other: not specified

Based on:

not specified

Sex:

not specified

Basis for effect level:

other: not specified

Remarks on result:

other: not specified

Fetal abnormalities

Abnormalities:

not specified

Localisation:

other: not specified

Description (incidence and severity):

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Treatment related:

not specified

Relation to maternal toxicity:

not specified

Dose response relationship:

not specified

Relevant for humans:

not specified

Applicant's summary and conclusion

Conclusions:

The No Observed Adverse Effect Level (NOAEL) of Sodium Lauryl Sulphate for developmental toxicity in New Zealand White Rabbit was observed at dose concentration of >600 mg/kg bw/day

Executive summary:

The purpose of this study was to evaluate the toxicity of Sodium Lauryl Sulphate as alcohol sulphate in New Zealand White Rabbit. Aqueous solution of Sodium Lauryl Sulphate was administered to pregnant New Zealand White Rabbit by oral intubation from Day 6 to 18 of pregnancy at a dose concentration of 0, 0.2, 2.0, 300 or 600 mg/kg/ day. All the animals were observed daily for signs of malreaction.

No minorvisceral and skeletal anomalies were observed. Hence the NOAEL was considered to be >600 mg/kg bw/day.