Sodium octane-1-sulphonate monohydrate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Endpoint waived due to existence of study equivalent/similar to OECD 414; Palmer et al. (1974)

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because a pre-natal developmental toxicity study is available

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
A study equivalent/similar to OECD 414 (Prenatal Developmental Toxicity Study; Palmer et al. 1974) was performed on a substance utilised in this dossier for Read-Across purposes (sodium dodecyl sulphate), therefore negating the need to commisssion an additional toxicity to reproduction study. As per Regulation (EC) 1907/2006, Annex VII, Part 8.7.1, Column 2 - the study/ies do(es) not generally need to be conducted if:
a pre-natal developmental toxicity study (Annex IX, 8.7.2: Pre-natal developmental toxicity study, one species, most appropriate route of administration, having regard to the likely route of human exposure - B.31 of the Commission Regulation on test methods as specified in Article 13(3) or OECD 414) is available.

Effect on fertility: via oral route

Endpoint conclusion:

no study available

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

A study equivalent/similar to OECD 414 (Prenatal Developmental Toxicity Study; Palmer et al. 1974) was performed on a substance utilised in this dossier for Read-Across purposes (alcohol sulphate), therefore negating the need to commission an additional toxicity to reproduction study. As per Regulation (EC) 1907/2006, Annex VII, Part 8.7.1, Column 2 - the study/ies do(es) not generally need to be conducted if:

a pre-natal developmental toxicity study (Annex IX, 8.7.2: Pre-natal developmental toxicity study, one species, most appropriate route of administration, having regard to the likely route of human exposure - B.31 of the Commission Regulation on test methods as specified in Article 13(3) or OECD 414) is available.

Effects on developmental toxicity

Description of key information

NOAEL for maternal toxicity: 300 mg/kg bw/day; NOAEL for developmental toxicity > 600 mg/kg bw/day; equivalent/similar to OECD 414; Palmer et al, 1974.

Link to relevant study records

Reference

Reference 1

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

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

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

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

Dose / conc.:

0.2 mg/kg bw/day (nominal)

Dose / conc.:

2 mg/kg bw/day (nominal)

Dose / conc.:

300 mg/kg bw/day (nominal)

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

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.

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.

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.

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

Abnormalities:

no effects observed

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.

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

Abnormalities:

no effects observed

Developmental effects observed:

no

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)

 

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.

Reference 2

Endpoint:

developmental toxicity

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH - See document attached in Section 13.2 for analogue read-across justification.

Reason / purpose for cross-reference:

read-across source

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

Key result

Abnormalities:

no effects observed

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

Key result

Abnormalities:

no effects observed

Key result

Developmental effects observed:

no

Conclusions:

The lowest NOAEL that could be determined for maternal toxicity was 300 mg/kg/day based on retarded weight gain 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.

The target result corresponds to the source result from a study on a structural analogue.

Executive summary:

See document attached in Section 13.2 for analogue read-across justification.

Alcohol sulphate was examined for potential teratogenic and embryotoxic activity in rats.  The test item was administered by oral gavage during days 6-15 pregnancy.  Dosages employed were 0.2, 2.0, 300 and 600 mg/kg/day with each group consisting of 20 female individuals (CRL:CD).

 

Mild 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 retarded weight gain. Rats showed no treatment-related total litter losses. Values for litter size and foetal loss were unaffected even at dosages providing evidence of maternal toxicity (600 mg/kg/day).

 

The incidence of major, minor, visceral and skeletal abnormalities was unaffected in rat pups.  A statistically significant reduction in the number of pups with extra ribs was observed in the 600 mg/kg/day test group.  The significance of this value was largely attributable to a relatively high incidence of extra-ribbed pups among the control group.  The number of pups with additional ribs for all test groups was within the expected normal laboratory range.

 

The lowest NOAEL that could be determined for maternal toxicity was 300 mg/kg/day based on retarded weight gain 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.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

300 mg/kg bw/day

Study duration:

subchronic

Species:

rabbit

Quality of whole database:

A reliable study consistent with information requirements at the registered tonnage band is utilised to fulfill this endpoint requirement.

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Sodium dodecyl sulphate (read-across source substance) 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.

Mode of Action Analysis / Human Relevance Framework

Not applicable, no reproductive or developmental effects observed in the available study.

Justification for classification or non-classification

The substance does not meet the criteria for classification in accordance with Regulation (EC) No 1272/2008 (CLP).