Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Assessment of the teratogenic potential of surfactants - Part I - LAS, AS and CLD
Author:
Palmer AK, Readshaw MA, Neuff AM
Year:
1975
Bibliographic source:
Toxicology, 3 91-106

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
lack of details on test substance, intervals in dose range
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Alcohol sulphate
- Physical state: no data
- Purity test date: no data

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
According to guideline.
TEST ANIMALS
- Source: East Anglian Rabbitries, Colchester, UK
- Age at study initiation: no data
- Housing: individually in metal cages with wire mesh floors.
- Diet: ad libitum
- Water: ad libitum
- weight and age: according to guideline

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18+/-2

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
Prepared daily as a series of graded aqueous solutions so that all groups were dosed with a standard volume.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
According to guideline.
Duration of treatment / exposure:
Day 6-18 of pregnancy
Frequency of treatment:
Daily
Duration of test:
Day 1-29
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.2, 2, 300 and 600 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
13
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale:Lowest 2 doses selected to provide a factor of 1-2 and 10-20 times the likely maximum human intake. The highest 2 doses were considered likely to impair maternal economy and provoke some obvious adverse effects.

Examinations

Maternal examinations:
According to guideline.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: No data
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No
Statistics:
Differences in group mean litter values were analysed by non-parametric methods (Wilcoxon test).
Historical control data:
No. of foetuses examined: 36,508
Major malformations (%): 0.74
Minor visceral anomalies (%): 2.53
Minor skeletal anomalies (%): 8.60

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
Deaths: 2/13 (controls); 1/13 (- intubation error -2mg/kg bw); 1/13 (300 mg/kg bw); 11/13 (600 mg/kg bw)
Bodyweight: retarded gain at 0.2 and 300 mg/kg bw/day; loss at 600 mg/kg bw/day.
Total litter loss: 1 at 0.2 mg/kg bw/day and 2 at 300 mg/kg bw/day
Toxic effects were generally associated with a principal disturbance of the gastrointestinal tract. Affected rabbits showed diarrhoa, anorexia, weight loss and cachexia prior to death. Total litter loss (abortion and/or total resorption) tended to occur as a secondary consequence of the primary effect on the mother.

Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
300 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOAEL
Effect level:
> 600 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
At maternally toxic doses there was an increased foetal loss and reduced litter size, due almost entirely to the total littler losses. That the latter were secondary consequence of maternal reaction was indicated by the fact that among rabbits bearing some young at termination litter parameters were comparable with (or not unduly different from) control values. At non-toxic dosages, or at dosages provoking only slight to moderate maternal reaction, values for litter size and foetal loss were essentially unaffected.
There wereno dose related increases in the number of abnormalities.
(please refer to attached tables)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
No maternal toxicity and no developmental toxicity up to 300 and 600 mg/kg/day, respectively.