Sodium octane-1-sulphonate monohydrate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH - Refer to Section 13.2 for read-across justification document

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1974

Report date:

1974

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

no

Remarks:

Study pre-dates GLP

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Alcohol sulphate

IUPAC Name:

Alcohol sulphate

Test material form:

not specified

Details on test material:

Name: Alcohol sulphate
Physical state: no data
Purity test date: no data

Supplier: Lion Fat & Oil Co. Ltd., Tokyo, Japan

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: East Anglian Rabbitries, Colchester, England
- Age at study initiation: Not reported
- Weight at study initiation: Not reported
- Fasting period before study: Not reported
- Housing: Individually in metal cage with wire mesh floor and maintained at 18 ± 2 ºC and 50 ± 5 % RH.
- Diet (e.g. ad libitum): Ad lib (SG-1 diet)
- Water (e.g. ad libitum): Ad lib
- Acclimation period: Not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 2 ºC
- Humidity (%): 50 ± 5 % RH
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

IN-LIFE DATES: From: To: Not reported

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Solutions were prepared daily as a series of graded aqueous solutions so that within each study animals in all groups were dosed orally by intragastric intubation at a standard volume. Control animals were dosed with water.

DIET PREPARATION
- Rate of preparation of diet (frequency): N/A
- Mixing appropriate amounts with (Type of food): N/A
- Storage temperature of food: N/A

VEHICLE
- Justification for use and choice of vehicle (if other than water): N/A
- Concentration in vehicle: N/A
- Amount of vehicle (if gavage): Not reported
- Lot/batch no. (if required): N/A
- Purity: N/A

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

N/A

Details on mating procedure:

- Impregnation procedure: Co-housed - details not reported
- Proof of pregnancy: Observation of coitus

Duration of treatment / exposure:

Dosing commenced on Day 6 (Day 0 = confirmation of mating) and continued up to and including Day 18

Frequency of treatment:

Daily

Duration of test:

29 days

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0.2 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

2 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

300 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

600 mg/kg bw/day (nominal)

No. of animals per sex per dose:

Females: 13

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: 0.2 and 2.0 mg/kg/day were chosen as likely maximum human intake estimates (from detergents). 300 and 600 mg/kg/day were investigated to provoke obvious adverse effects, the pattern of which would help in assessing the relevance of any marginal differences that might occur at the lower tested concentrations.
- Rationale for animal assignment (if not random): Not reported
- Other: N/A

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule: 'Regularly'

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): N/A

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): N/A

POST-MORTEM EXAMINATIONS: Yes
- Conducted on all animals either at death (during the test) or at test termination.

OTHER: N/A

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
- Other: N/A

Fetal examinations:

- External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [all per litter]
- Skeletal examinations: Yes: [all per litter]
- Head examinations: No

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

General toxicity (maternal animals)

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Toxic effects were generally associated with a principal disturbance of the gastrointestinal tract. Affected rabbits showed diarrhoea, anorexia, weight loss and cachexia prior to death (moribund animals were killed for humane reasons); total litter loss (abortion and/or total resorption) tended to occur as a secondary consequence of the primary effect on the mother.

Dermal irritation (if dermal study):

not examined

Mortality:

mortality observed, treatment-related

Description (incidence):

Mortality was only observed in the highest two concentration groups; 1/13 and 11/13 in the 300 and 600 mg/kg/day test groups, respectively.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Retarded weight gain observed in the 300 mg/kg/day test group and weight loss observed in the 600 mg/kg/day.

Food consumption and compound intake (if feeding study):

not examined

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:

not examined

Gross pathological findings:

not examined

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Details on results:

Strong toxic effects were observed in rabbits treated at the highest test concentration including; diarrhoea, anorexia, weight loss and cachexia prior to death. 11/13 individuals died during the course of the study in the 600 mg/kg/day test group, in comparison to 2/13 and 1/13 in the control and 300 mg/kg/day test groups, respectively.

Maternal developmental toxicity

Number of abortions:

no effects observed

Pre- and post-implantation loss:

no effects observed

Total litter losses by resorption:

no effects observed

Early or late resorptions:

no effects observed

Dead fetuses:

no effects observed

Changes in pregnancy duration:

not examined

Changes in number of pregnant:

no effects observed

Other effects:

not examined

Details on maternal toxic effects:

At the maternally toxic dose of 600 mg/kg/day, there was an increase in foetal loss and reduced litter size, due almost entirely to total litter losses. These factors were deemed to be a secondary consequence of the maternal reaction to the test item, indicated by the fact that among the rabbits bearing young at termination litter parameters were comparable to the control group.

Effect levels (maternal animals)

Key result

Dose descriptor:

NOAEL

Effect level:

300 mg/kg bw/day (nominal)

Based on:

test mat.

Basis for effect level:

body weight and weight gain

mortality

Maternal abnormalities

Abnormalities:

no effects observed

Results (fetuses)

Fetal body weight changes:

no effects observed

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, non-treatment-related

Description (incidence and severity):

A higher incidence of rabbit pups with extra ribs in the 300 mg/kg/day treatment group was observed. The degree of incidence was within the normal historical laboratory range so this effect was deemed to be non-significant.

Visceral malformations:

no effects observed

Other effects:

not examined

Details on embryotoxic / teratogenic effects:

The incidence of major, minor, visceral and skeletal abnormalities was unaffected in rabbit pups. A statisticaly significant increase in the number of pups with extra ribs was observed in the 300 mg/kg/day test group. The degree of incidence was within the normal historical laboratory range so this effect was deemed to be non-significant.

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Effect level:

> 600 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Remarks on result:

not determinable due to adverse toxic effects at highest dose / concentration tested

Fetal abnormalities

Abnormalities:

no effects observed

Overall developmental toxicity

Developmental effects observed:

no

Any other information on results incl. tables

Table 2       Summary of maternal performance

 

Observation	Number of animals at dosage
	Control	0.2 mg/kg/day	2.0 mg/kg/day	300 mg/kg/day	600 mg/kg/day
Mated	13	13	13	13	13
Died	2	0	1^	1	11
Non-pregnant	1	1	2	1	0
Total litter loss	0	1	0	2	0
With viable young	10	11	10	9	2
Bodyweight change	-	retarded gain	-	retarded gain	loss

 

Table 3       Group mean litter data

 

Dosage (mg/kg/day)	Number of litters ^	Litter size (of viable young)	Embryonic deaths	Implantations	Corpora lutea	Embryonic loss %		Litter weight (g)	Foetal weight (g)
						Pre-implantation	Post-implantation
0	A=B=10	7.3	0.5	7.8	10.7	27.2	4.3	295.7	43.1
0.2	A=12 B=11	7.1 7.7	0.8 0.4	7.8 8.1	9.2 9.5	12.8 12.5	13.9 6.1	- 331.3	- 43.5
2.0	A=B=10	9.0	1.3	10.3	10.7	3.8	12.8	332.6	37.1
300	A=11 B=9	7.7 9.4	2.4 0.6	10.1 10.0	10.8 10.8	6.3 6.8	22.7 5.6	- 357.3	- 37.9
600	A=B=2	8.0	2.0	10.0	11.0	9.1	18.2	297.2	37.1

^ Mean A = includes all surviving animals showing evidence of implantation, including those with total litter loss

^ Mean B = includes only animals bearing viable young at termination

 

Table 4       Group mean incidence of major malformations and minor anomalies

 

Dose (mg/kg/day)	Number of young									Incidence of pups with extra lumbar ribs (mean %) ^
	Major malformations			Minor anomalies^
	Examined	Affected		Gross or visceral			Skeletal
		Total number	Mean %	Examined	Affected		Examined	Affected
					Total number	Mean %		Total number	Mean %
0	73	0	0	73	5	6.3	73	2	2.2	33.6
0.2	85	0	0	85	0	0	85	13	13.1	46.9
2.0	90	1	1.1	89	7	8.6	89	20	22.9	79.6*
300	85	0	0	85	3	4.2	85	8	9.4	63.5
600	16	0	0	16	1	5.6	16	2	14.3	85.7

^ young showing major malformations excluded

* Wilcoxon test (p < 0.05)

 

Applicant's summary and conclusion

Conclusions:

The lowest NOAEL that could be determined for maternal toxicity was 300 mg/kg/day based on adverse clinical signs and mortality observed in the 600 mg/kg/day group.
 
The NOAEL for developmental toxicity could not be established due to the absence of adverse toxic effects at the highest concentration i.e. > 600 mg/kg/day.

This result is appropriate under a read-across approach for applicability to the target substance sodium octane-1-sulphonate monohydrate.

Executive summary:

Alcohol sulphate was examined for potential teratogenic and embryotoxic activity in rabbits. The test item was administered by oral gavage during days 6-18 pregnancy. Dosages employed were 0.2, 2.0, 300 and 600 mg/kg/day with each group consisting of 13 female individuals (New Zealand White).

 

Maternal toxicity was observed in animals treated at 600 mg/kg/day and was generally with a principle disturbance of the gastrointestinal tract, resulting in diarrhoea, anorexia, weight loss and cachexia prior to death.At the maternally toxic dose of 600 mg/kg/day, there was an increase in foetal loss and reduced litter size, due almost entirely to total litter losses. These factors were deemed to be a secondary consequence of the maternal reaction to the test item, indicated by the fact that among the rabbits bearing young at termination litter parameters were comparable to the control group

 

The incidence of major, minor, visceral and skeletal abnormalities was unaffected in rabbit pups. A statistically significant increase in the number of pups with extra ribs was observed in the 300 mg/kg/day test group. The degree of incidence was within the normal historical laboratory range, so this effect was deemed to be non-significant.

 

The lowest NOAEL that could be determined for maternal toxicity was 300 mg/kg/daybased on adverse clinical signs and mortality observed in the 600 mg/kg/day group.

 

The NOAEL for developmental toxicity could not be established due to the absence of adverse toxic effects at the highest concentration i.e. > 600 mg/kg/day.